Original Article
Glycosaminoglycans Are Involved in the Adhesion of Candida albicans and Malassezia Species to Keratinocytes But Not to Dermal Fibroblasts
Los glicosaminoglicanos se encuentran implicados en la adherencia de Candida albicans y Malassezia spp. a queratinocitos, pero no a fibroblastos dérmicos
H. Ordialesa,b, F. Vázquez-Lópezc,d, M. Pevidae, B. Vázquez-Losadac, F. Vázqueza,b,f, L.M. Quirósa,b, C. Martína,b,
Corresponding author
a Instituto Universitario Fernández-Vega (IUFV), Universidad de Oviedo, Oviedo, Asturias, Spain
b Departamento de Biología Funcional, Universidad de Oviedo, Oviedo, Asturias, Spain
c Servicio de Dermatología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
d Departamento de Medicina, Universidad de Oviedo, Oviedo, Asturias, Spain
e Centro Comunitario de Sangre y Tejidos del Principado de Asturias y CIBERER, U714, Oviedo, Asturias, Spain
f Servicio de Microbiología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
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"apellidos" => "Martín" "email" => array:1 [ 0 => "cmartincueto@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Instituto Universitario Fernández-Vega (IUFV), Universidad de Oviedo, Oviedo, Asturias, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Biología Funcional, Universidad de Oviedo, Oviedo, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Medicina, Universidad de Oviedo, Oviedo, Asturias, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centro Comunitario de Sangre y Tejidos del Principado de Asturias y CIBERER, U714, Oviedo, Asturias, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Microbiología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Los glicosaminoglicanos se encuentran implicados en la adherencia de <span class="elsevierStyleItalic">Candida albicans</span> y <span class="elsevierStyleItalic">Malassezia</span> spp. a queratinocitos, pero no a fibroblastos dérmicos" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 917 "Ancho" => 1333 "Tamanyo" => 62051 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The skin is colonized by a variety of microorganisms, including bacteria and, to a lesser extent, fungi, viruses, and parasites.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Numerous studies have described the importance of bacteria and their role in both maintaining skin homeostasis and contributing to certain types of skin infection. However, little is known about the mycobiome, the population of fungi that inhabit the body. Like bacteria, many fungi can have pathogenic effects if they proliferate excessively or the host's immune response is altered. Superficial mycoses are among the most prevalent diseases in the world, and the most commonly detected opportunistic fungi in these types of infections are yeasts of the genera <span class="elsevierStyleItalic">Malassezia</span> and <span class="elsevierStyleItalic">Candida</span>, followed by other fungi such as dermatophytes.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Of the fungi found on adult skin, the most abundant belong to the genus <span class="elsevierStyleItalic">Malassezia</span>. These yeasts obtain carbon exclusively from lipids, which they are unable to synthesize, and mainly colonize sebaceous areas of skin.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a> They account for more than 90% of commensal fungi present on the skin. The most abundant species are <span class="elsevierStyleItalic">Malassezia</span><span class="elsevierStyleItalic">globosa</span>, <span class="elsevierStyleItalic">Malassezia</span><span class="elsevierStyleItalic">restricta</span>, and <span class="elsevierStyleItalic">Malassezia</span><span class="elsevierStyleItalic">sympodialis</span>. Despite their commensal nature, these species can also be associated with common skin disorders such as pityriasis versicolor and seborrheic dermatitis.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The genus <span class="elsevierStyleItalic">Candida</span> is a heterogeneous group of commensal fungi found on the skin, nails, and mucous membranes of 70% of individuals. However, in immunodeficient individuals, and in conditions conducive to immune compromise, they can become pathogens, causing superficial and even systemic infections with high mortality rates.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> Although about 20 <span class="elsevierStyleItalic">Candida</span> species are pathogens in humans, the vast majority of recorded candidiasis cases are caused by <span class="elsevierStyleItalic">Candida</span><span class="elsevierStyleItalic">albicans</span>. One characteristic of members of this genus is that they are polymorphic, existing in yeast form or as hyphae or pseudohyphae.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Through the skin and mucosae the human body is continuously exposed to a broad range of pathogens. To colonize these surfaces pathogens must first anchor themselves to receptors present in the host. This is a critical step that involves specific recognition between molecules on the surface of the microorganism and those that comprise the receptor.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> There are several cell-surface molecules that act as binding mediators, including carbohydrates, lipids, proteins, and proteoglycans (PGs).<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a> PGs are made up of a central protein molecule to which varying numbers of polysaccharide chains called glycosaminoglycans (GAGs) are attached. GAGs consist of varying numbers of disaccharide repeats. There are different types of GAGs, with distinct chemical structures. Two examples are heparan sulfate (HS) and chondroitin sulfate (CS), which are formed by binding of glucuronic acid (GlcA) to N-acetylglucosamine (in the case of HS) or to N-acetylgalactosamine (in the case of CS).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Subsequently, these chains undergo a series of post-transcriptional modifications that confer great structural diversity, enabling their involvement in numerous physiological and pathological processes.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> The interaction of GAGs with a broad range of ligands, including cytokines, growth factors, and enzymes, implicates them in processes such as cell adhesion and migration, regulation of morphogenesis, inflammation, and even cancer and various infectious processes.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18–20</span></a> The literature describes many situations in which GAGs facilitate pathogen binding to the surface of eukaryotic cells and in some case help achieve invasion, internalization, and dissemination of the pathogen.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">This study investigates the role of GAGs as receptors in the process of adhesion of 2 species of commensal skin fungi, <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> and <span class="elsevierStyleItalic">Malassezia</span> species, both of which act as opportunistic pathogens in certain circumstances. The aim of the study was to determine whether GAGs are involved in the adhesion of these microorganisms to epidermal keratinocytes and dermal fibroblasts, and to examine the role in these interactions of the main GAG species present on the cell surface. The findings could help to expand current knowledge of the molecular bases of adhesion, and propose novel anti-infective strategies that block a key initial step of the pathogenic process: pathogen adhesion to target tissues. The results may have broader relevance given that adhesion is also a prerequisite for many pathogens to deliver virulence factors into host cells.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cell lines, fungal strains, and culture conditions</span><p id="par0030" class="elsevierStylePara elsevierViewall">This research was carried out in accordance with the principles of the Declaration of Helsinki. Keratinocytes and fibroblasts were acquired from human biopsies from the tissue bank of the Community Blood and Tissue Center of Asturias after first obtaining written informed consent in accordance with Spanish laws on organ and tissue donation for research. Cells were cultured as previously indicated.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> and <span class="elsevierStyleItalic">Malassezia</span> species strains were obtained from clinical isolates provided by the Hospital Universitario Central de Asturias. <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> was grown at room temperature in Sabouraud (Difco) medium (BD, MD, USA) with chloramphenicol at a concentration of 50<span class="elsevierStyleHsp" style=""></span>μg/L. To obtain filamentous <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span>, medium containing 0.1% glucose, 1% glycine, and 0.1% yeast extract at pH 7.5 was incubated at 37<span class="elsevierStyleHsp" style=""></span>°C and 5% CO<span class="elsevierStyleInf">2</span> for 48<span class="elsevierStyleHsp" style=""></span>hours. <span class="elsevierStyleItalic">Malassezia</span> species were cultured at 37<span class="elsevierStyleHsp" style=""></span>°C in Sabouraud medium enriched with 1% olive oil and 1% Tween 20.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Fluorescence labeling</span><p id="par0040" class="elsevierStylePara elsevierViewall">After overnight incubation fungi were washed 4 times with PBS. Subsequently, the cultures were resuspended in a PBS solution containing 0.1<span class="elsevierStyleHsp" style=""></span>mg/mL fluorescein isothiocyanate (FITC; Sigma Aldrich, MO, USA) at an A<span class="elsevierStyleInf">600</span> of 0.5 and incubated in darkness for 1<span class="elsevierStyleHsp" style=""></span>hour at 37<span class="elsevierStyleHsp" style=""></span>°C. Next, the cultures were centrifuged, washed 4 times with PBS to remove excess FITC, and resuspended in PBS at an A<span class="elsevierStyleInf">600</span> of 0.5.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Adhesion assays</span><p id="par0045" class="elsevierStylePara elsevierViewall">Assays to evaluate fungal adhesion to cell monolayers were carried out in 24-well plates in which cell cultures were grown to 70–90% confluence. The culture medium was removed and the cells were washed twice with PBS and blocked with 10% fetal calf serum in Dulbecco modified Eagle's minimal essential medium (DMEM) (Gibco, Life Technologies, CA, USA) for 2<span class="elsevierStyleHsp" style=""></span>hours at 37<span class="elsevierStyleHsp" style=""></span>°C and 5% CO<span class="elsevierStyleInf">2</span>. Subsequently, the wells were washed with PBS, 200<span class="elsevierStyleHsp" style=""></span>μL of the suspension containing labeled fungi was added, and the volume was made up to 500<span class="elsevierStyleHsp" style=""></span>μL with DMEM medium. The mixture was then incubated for 90<span class="elsevierStyleHsp" style=""></span>minutes at 37<span class="elsevierStyleHsp" style=""></span>°C and 5% CO<span class="elsevierStyleInf">2</span>, after which the wells were washed twice with PBS to remove unbound fungi. Finally, the cultures were disaggregated using 1% SDS and the fluorescence of the attached fungi was measured with a LS55 fluorimeter (Perkin Elmer, MA, USA), using excitation and emission wavelengths of 488<span class="elsevierStyleHsp" style=""></span>nm and 560<span class="elsevierStyleHsp" style=""></span>nm, respectively. The values from the different experiments were normalized to adhesion values obtained in the absence of any treatment, which were assigned an arbitrary value of 100.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Inhibition of GAG synthesis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Cell cultures in 24-well plates grown to approximately 70% confluence were incubated overnight in DMEM containing 50<span class="elsevierStyleHsp" style=""></span>μg/mL rhodamine B (Sigma-Aldrich) and 30<span class="elsevierStyleHsp" style=""></span>μM genistein (Sigma-Aldrich) at 37<span class="elsevierStyleHsp" style=""></span>°C. The cultures were washed twice with PBS, cell integrity was evaluated under a light microscope, and adhesion assays were carried out as described in the previous paragraph.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Enzymatic digestion of GAG on the cell surface</span><p id="par0055" class="elsevierStylePara elsevierViewall">HS in cell cultures was digested by incubation in DMEM medium containing a mixture of heparinase I and III (500<span class="elsevierStyleHsp" style=""></span>mU/mL each; Sigma Aldrich) for 3<span class="elsevierStyleHsp" style=""></span>hours at 37<span class="elsevierStyleHsp" style=""></span>°C and 5% CO<span class="elsevierStyleInf">2</span>. CS digestion was performed in the same way, using 250<span class="elsevierStyleHsp" style=""></span>mU/mL chondroitinase ABC (Sigma Aldrich). Reactions were stopped by washing twice in PBS, cell integrity was assessed under a light microscope, and adhesion assays were then carried out as described above.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">All experiments were performed at least 3 times with at least 3 replicates per group. All data were analyzed using the Statistica program (Statsoft Inc.; Tulsa, OK, USA). Differences in mean values between 2 samples were compared using the Mann-Whitney U test, with significance set at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Inhibition of GAG biosynthesis: effect on yeast epidermal keratinocytes and dermal fibroblasts</span><p id="par0065" class="elsevierStylePara elsevierViewall">Treatment of keratinocytes with either rhodamine B or genistein inhibited the adhesion of both yeast and filamentous forms of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span>. However, the intensity of the effect was dependent on the inhibitor. The strongest effect was observed for rhodamine B, while genistein only reduced adhesion values by a mean of 15% in both cases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). In <span class="elsevierStyleItalic">Malassezia</span> species, rhodamine B had an effect similar to that observed for <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span>, whereas treatment with genistein increased adhesion by around 17% compared with controls (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Addition of the same 2 inhibitors to dermal fibroblasts produced radically different results. Inhibition of adhesion was not observed in any case. Curiously, adhesion increased in all microbial forms analyzed. The increase in adhesion observed following genistein treatment was statistically significant (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Enzymatic digestion of GAG: effect on yeast adhesion to epidermal keratinocytes and dermal fibroblasts</span><p id="par0075" class="elsevierStylePara elsevierViewall">Treatment of epidermal keratinocytes with heparinases I and III resulted in no significant differences in yeast adhesion with respect to controls, except in the case of <span class="elsevierStyleItalic">Malassezia</span> species, which showed an 80% increase in adhesion after elimination of HS from the surface of keratinocytes (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Degradation of CS with chondroitinase ABC had the opposite effect: adhesion of <span class="elsevierStyleItalic">Malassezia</span> species was unchanged, but adhesion of both yeast and filamentous forms of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> was significantly decreased (27% reduction in adhesion in both cases; <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Digestion of HS cell on the cell surface of fibroblasts by treatment with heparinases I and III resulted in an increase in adhesion in all cases, an effect that was strongest for <span class="elsevierStyleItalic">Malassezia</span> species and was stronger for the filamentous versus the yeast form of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Degradation of CS in fibroblasts resulted in no significant changes in adhesion with respect to controls, except in the case of the filamentous form of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span>, in which adhesion increased significantly (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B).</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">PGs in general and their GAG chains in particular are involved in different infectious processes, in which they act as receptors for many pathogens.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The epidermis, the most superficial layer of the skin, is comprised mainly of keratinocytes, and its main function is that of a barrier that maintains homeostasis and protects against external aggressions including colonization and infection by pathogens. Immediately beneath the epidermis is the dermis, in which fibroblasts are found. This layer is less exposed to environmental factors and microorganisms. The participation of GAGs in microbial pathogenesis is conditioned by their structure,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and this varies depending on the cell type and its physiological state.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> It is therefore of interest to investigate the role of these molecules as receptors in fungal infections.</p><p id="par0090" class="elsevierStylePara elsevierViewall">To evaluate the involvement of GAGs in the interaction of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> and <span class="elsevierStyleItalic">Malassezia</span> species with epidermal keratinocytes and dermal fibroblasts, we inhibited GAG synthesis with rhodamine B and genistein.</p><p id="par0095" class="elsevierStylePara elsevierViewall">These inhibitors exerted distinct effects. In keratinocytes, rhodamine treatment markedly inhibited fungal adhesion. By contrast, genistein only mildly inhibited adhesion of cellular forms of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span>, and increased the adhesion of <span class="elsevierStyleItalic">Malassezia</span> species. Treatment of fibroblasts with the aforementioned inhibitors had no inhibitory effect on fungal adhesion, which was actually increased, in some cases significantly. However, the lack of significant differences was likely due to the variability of the data. The different effects of the inhibitors used are probably due to their distinct modes of action. Rhodamine B inhibits initiation and elongation of GAG chains,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,23,24</span></a> while genistein inhibits the activity of epidermal growth factor receptor kinase, which is required for complete expression of the genes that encode the enzymes involved in GAG production.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> However, it has been reported that the effects of genistein on GAG biosynthesis depend on GAG type and location.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> Taken together, these results show that GAGs appear to act as receptors for potentially pathogenic yeasts in keratinocytes, but not fibroblasts.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Enzymatic degradation of GAGs using different lysases showed that in keratinocytes CS appears to be more important for <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> adhesion, while elimination of HS promoted adhesion of <span class="elsevierStyleItalic">Malassezia</span> species. In dermal fibroblasts, no decrease in adhesion was observed after treatment with either inhibitor. In fact, in all cases increased adhesion was observed after elimination of HS from the cell surface. Elimination of CS by treatment with chondroitinase ABC promoted adhesion of filamentous <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans.</span> Increased adhesion of yeast to skin cells after GAG degradation could favor greater exposure of another class of eukaryotic receptors involved in binding. On the other hand, the limited effect of degradation of individual GAG species on fungal adhesion could be indicative of cooperative phenomena involving both GAG species, as well as interaction with other receptors, as described in other epithelia.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In conclusion, the present findings suggest that keratinocyte cell surface GAGs participate in <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Malassezia</span> adhesion, probably in a cooperative manner. By contrast, in fibroblasts these molecules do not appear to play the same role and, in fact, interfere with adhesion, suggesting that adhesion is mediated by other receptors in these cells. The use of antifungal agents to treat these types of infections can lead to long-term resistance, underscoring the need for new therapeutic alternatives. The present findings open new avenues for the development of anti-adhesion strategies including competitive adhesin molecules that mimic GAGs, specific antibodies, and blockade of adhesin or cell receptor synthesis.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This work was funded by the 2019 ‘AEDV Investigates’ (‘AEDV investiga’) prize, awarded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Healthy Skin Foundation</span>(Fundación Piel Sana) of the Spanish Academy of Dermatology and Venereology (AEDV).</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of Interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1542268" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1542266" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1395152" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1542267" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1395153" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Cell lines, fungal strains, and culture conditions" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Fluorescence labeling" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Adhesion assays" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Inhibition of GAG synthesis" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Enzymatic digestion of GAG on the cell surface" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 7 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Inhibition of GAG biosynthesis: effect on yeast epidermal keratinocytes and dermal fibroblasts" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Enzymatic digestion of GAG: effect on yeast adhesion to epidermal keratinocytes and dermal fibroblasts" ] ] ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-18" "fechaAceptado" => "2021-02-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1395152" "palabras" => array:5 [ 0 => "Mycosis" 1 => "Glycosaminoglycans" 2 => "Infection" 3 => "Heparan sulfate" 4 => "Chondroitin sulfate" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1395153" "palabras" => array:5 [ 0 => "Micosis" 1 => "Glicosaminoglicanos" 2 => "Infección" 3 => "Heparán sulfato" 4 => "Condroitín sulfato" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Background and objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Superficial mycoses are some of the most common diseases worldwide. The usual culprits—yeasts belonging to the genera <span class="elsevierStyleItalic">Malassezia</span> and <span class="elsevierStyleItalic">Candida</span>—are commensal species in the skin that can cause opportunistic infections. We aimed to determine whether these yeasts use glycosaminoglycans (GAGs) as adhesion receptors to mediate binding to epithelial cells.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In keratinocyte and dermal fibroblast cultures, we used rhodamine B and genistein to inhibit GAG synthesis to study the role these molecules play in the adhesion of <span class="elsevierStyleItalic">Candida albicans</span> and <span class="elsevierStyleItalic">Malassezia</span> species to cells. We also analyzed GAG involvement by means of enzyme digestion, using specific lyases.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Rhodamine B partially inhibited the adhesion of both fungi to keratinocytes but not to fibroblasts. Selective digestion of heparan sulfate enhanced the binding of <span class="elsevierStyleItalic">Malassezia</span> species to keratinocytes and of both fungi to fibroblasts. Chondroitin sulfate digestion decreased <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> adhesion to keratinocytes, but increased the adhesion of the filamentous forms of this species to fibroblasts.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cell surface GAGs appear to play a role in the adhesion of <span class="elsevierStyleItalic">C</span><span class="elsevierStyleItalic">albicans</span> and <span class="elsevierStyleItalic">Malasezzia</span> species to keratinocytes. In contrast, their adhesion to fibroblasts appears to be enhanced by GAG inhibition, suggesting that some other type of receptor is the mediator.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes y objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Las micosis superficiales son algunas de las enfermedades más comunes en todo el mundo, siendo los agentes causales más frecuentes las levaduras de los géneros <span class="elsevierStyleItalic">Malassezia</span> y <span class="elsevierStyleItalic">Candida,</span> comensales habituales de la piel que pueden actuar como patógenos oportunistas. El objetivo de este trabajo es investigar si los glicosaminoglicanos (GAG) de las células epiteliales son utilizados por estos microrganismos como receptores de adhesión a las mismas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materiales y métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se utilizaron cultivos de queratinocitos y fibroblastos dérmicos. La participación de los GAG en la adhesión de <span class="elsevierStyleItalic">Candida albicans (C. albicans)</span> y <span class="elsevierStyleItalic">Malassezia</span> spp. se estudió mediante inhibición específica de la síntesis de estas moléculas empleando rodamina B o genisteína. También se analizó mediante digestión enzimática in situ empleando liasas específicas.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con rodamina B produjo una inhibición parcial de la adherencia de ambas especies fúngicas a queratinocitos, pero no a fibroblastos. La digestión selectiva del heparán sulfato produjo un aumento de la unión de <span class="elsevierStyleItalic">Malassezia</span> a los queratinocitos y de ambas especies a los fibroblastos. La digestión del condroitín sulfato redujo la unión de <span class="elsevierStyleItalic">C. albicans</span> en los queratinocitos, pero favoreció la unión de la forma filamentada de esta levadura en los fibroblastos.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los GAG de superficie celular de queratinocitos parecen estar implicados en la adherencia de <span class="elsevierStyleItalic">Candida</span> y <span class="elsevierStyleItalic">Malasezzia</span> a la superficie celular. En los fibroblastos, por el contrario, su eliminación favorece la adherencia, sugiriendo la implicación de otro tipo de receptores.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ordiales H, Vázquez-López F, Pevida M, Vázquez-Losada B, Vázquez F, Quirós LM, et al. Los glicosaminoglicanos se encuentran implicados en la adherencia de <span class="elsevierStyleItalic">Candida albicans</span> y <span class="elsevierStyleItalic">Malassezia</span> spp. a queratinocitos, pero no a fibroblastos dérmicos. Actas Dermosifiliogr. 2021;112:619–624.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1436 "Ancho" => 2091 "Tamanyo" => 141901 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Effect of inhibition of GAG biosynthesis on yeast adhesion to skin cells. Graphs depict the effect of treatment with rhodamine B (dark bars) and genistein (light bars) on adhesion to keratinocytes (A) and fibroblasts (B). Data were normalized to yeast adhesion values recorded in untreated cells, to which an arbitrary value of 100 was assigned. Error bars represent standard deviation.</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">*<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1352 "Ancho" => 2091 "Tamanyo" => 142961 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Effect of enzymatic degradation of cellular GAG on yeast adhesion to skin cells. Graphs depict the inhibitory effect of treatment with heparinases I and III (dark bars) or chondroitinase ABC (light bars) on yeast adhesion to keratinocytes (A) and fibroblasts (B). Data were normalized to yeast adhesion values recorded in untreated cells, to which an arbitrary value of 100 was assigned. Error bars represent standard deviation.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">*<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] 2 => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 917 "Ancho" => 1333 "Tamanyo" => 62051 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dialogue between skin microbiota and immunity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Y. Belkaid" 1 => "J.A. Segre" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1260144" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2014" "volumen" => "346" "paginaInicial" => "954" "paginaFinal" => "959" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25414304" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diverse human skin fungal communities in children converge in adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.H. Jo" 1 => "C. Deming" 2 => "E.A. Kennedy" 3 => "S. Conlan" 4 => "E.C. Polley" 5 => "W.I. Ng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jid.2016.05.130" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2016" "volumen" => "136" "paginaInicial" => "2356" "paginaFinal" => "2363" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27476723" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and fungal species distribution of superficial mycoses in Northeast Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.P. Silva-Rocha" 1 => "M.F. de Azevedo" 2 => "G.M. Chaves" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.mycmed.2016.08.009" "Revista" => array:6 [ "tituloSerie" => "J Mycol Med" "fecha" => "2017" "volumen" => "27" "paginaInicial" => "57" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27663203" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of dermatomycoses in southwest Poland, years 2011–2016" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Gawdzik" 1 => "K. Nowogrodzka" 2 => "A. Hryncewicz-Gwóźdź" 3 => "J. Maj" 4 => "J. Szepietowski" 5 => "A. Jankowska-Konsur" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/ada.2018.80615" "Revista" => array:7 [ "tituloSerie" => "Postepy Dermatol Alergol" "fecha" => "2019" "volumen" => "36" "paginaInicial" => "604" "paginaFinal" => "608" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31839778" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109708019360" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Host responses to <span class="elsevierStyleItalic">Malassezia</span> spp. in the mammalian skin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Sparber" 1 => "S. LeibundGut-Landmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fimmu.2017.01614" "Revista" => array:5 [ "tituloSerie" => "Front Immunol" "fecha" => "2017" "volumen" => "8" "paginaInicial" => "1614" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29213272" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Malassezia</span> ecology, pathophysiology, and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Theelen" 1 => "C. Cafarchia" 2 => "G. Gaitanis" 3 => "I.D. Bassukas" 4 => "T. Boekhout" 5 => "T.L. Dawson Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/mmy/myx134" "Revista" => array:6 [ "tituloSerie" => "Med Mycol" "fecha" => "2018" "volumen" => "56" "numero" => "Suppl. 1" "paginaInicial" => "S10" "paginaFinal" => "S25" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Looking into <span class="elsevierStyleItalic">Candida albicans</span> infection, host response, and antifungal strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Y. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/21505594.2014.1000752" "Revista" => array:6 [ "tituloSerie" => "Virulence" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "307" "paginaFinal" => "308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25590793" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skin immunity to <span class="elsevierStyleItalic">Candida albicans</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.W. Kashem" 1 => "D.H. Kaplan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.it.2016.04.007" "Revista" => array:6 [ "tituloSerie" => "Trends Immunol" "fecha" => "2016" "volumen" => "37" "paginaInicial" => "440" "paginaFinal" => "450" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27178391" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida–Epithelial interactions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.P. Richardson" 1 => "J. Ho" 2 => "J.R. Naglik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/jof4010022" "Revista" => array:4 [ "tituloSerie" => "J Fungi (Basel)" "fecha" => "2018" "volumen" => "4" "paginaInicial" => "22" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interactions of <span class="elsevierStyleItalic">Candida albicans</span> with host epithelial surfaces" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.W. Williams" 1 => "R.P. Jordan" 2 => "X.Q. Wei" 3 => "C.T. Alves" 4 => "M.P. Wise" 5 => "M.J. Wilson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3402/jom.v5i0.22434" "Revista" => array:4 [ "tituloSerie" => "J Oral Microbiol" "fecha" => "2013" "volumen" => "5" "paginaInicial" => "22434" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Candida albicans</span>. Biology, molecular characterization, pathogenicity, and advances in diagnosis and control—an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Dadar" 1 => "R. Tiwari" 2 => "K. Karthik" 3 => "S. Chakraborty" 4 => "Y. Shahali" 5 => "K. Dhama" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.micpath.2018.02.028" "Revista" => array:6 [ "tituloSerie" => "Microb Pathog" "fecha" => "2018" "volumen" => "117" "paginaInicial" => "128" "paginaFinal" => "138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29454824" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Action mechanisms of probiotics on <span class="elsevierStyleItalic">Candida</span> spp. and candidiasis prevention: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.C. Ribeiro" 1 => "R.D. Rossoni" 2 => "P.P. de Barros" 3 => "J.D. Santos" 4 => "L.R.O. Fugisaki" 5 => "M.P.V. Leão" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jam.14511" "Revista" => array:5 [ "tituloSerie" => "J Appl Microbiol" "fecha" => "2020" "volumen" => "129" "paginaInicial" => "175" "paginaFinal" => "185" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bacterial adhesion and entry into host cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Pizarro-Cerdá" 1 => "P. Cossart" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2006.02.012" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2006" "volumen" => "124" "paginaInicial" => "715" "paginaFinal" => "727" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16497583" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microbial adherence to and invasion through proteoglycans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.S. Rostand" 1 => "J.D. Esko" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/IAI.65.1.1-8.1997" "Revista" => array:6 [ "tituloSerie" => "Infect Immun" "fecha" => "1997" "volumen" => "65" "paginaInicial" => "1" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8975885" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glycosaminoglycans are involved in bacterial adherence to lung cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Rajas" 1 => "L.M. Quirós" 2 => "M. Ortega" 3 => "E. Vázquez-Espinosa" 4 => "J. Merayo-Lloves" 5 => "F. Vazquez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12879-017-2418-5" "Revista" => array:5 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2017" "volumen" => "17" "paginaInicial" => "319" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28464847" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteoglycan form and function: a comprehensive nomenclature of proteoglycans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.V. Iozzo" 1 => "L. Schaefer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.matbio.2015.02.003" "Revista" => array:6 [ "tituloSerie" => "Matrix Biol" "fecha" => "2015" "volumen" => "42" "paginaInicial" => "11" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25701227" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteoglycans and sulfated glycosaminoglycans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.D. Esko" 1 => "K. Kimata" 2 => "U. Lindahl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "editores" => "A.Varki, R.D.Cummings, J.D.Esko, H.H.Freeze, P.Stanley, C.R.Bertozzi" "titulo" => "Essentials of glycobiology" "edicion" => "2nd ed." "serieFecha" => "2009" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparan sulfate proteoglycans: structure, protein interactions and cell signaling" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.L. Dreyfuss" 1 => "C.V. Regatieri" 2 => "T.R. Jarrouge" 3 => "R.P. Cavalheiro" 4 => "L.O. Sampaio" 5 => "H.B. Nader" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/s0001-37652009000300007" "Revista" => array:5 [ "tituloSerie" => "An Acad Bras Cienc" "fecha" => "2009" "volumen" => "81" "paginaInicial" => "409" "paginaFinal" => "429" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glycosaminoglycans in infectious disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Kamhi" 1 => "E.J. Joo" 2 => "J.S. Dordick" 3 => "R.J. Linhardt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/brv.12034" "Revista" => array:6 [ "tituloSerie" => "Biol Rev Camb Philos Soc" "fecha" => "2013" "volumen" => "88" "paginaInicial" => "928" "paginaFinal" => "943" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23551941" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alterations of heparan sulfate proteoglycans in cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I. Fernández-Vega" 1 => "B. García" 2 => "O. García-Suárez" 3 => "S. Castañón" 4 => "L.M. Quirós" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4172/2168-958X.1000109" "Revista" => array:6 [ "tituloSerie" => "J Glycobiol" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "1" "paginaFinal" => "6" "itemHostRev" => array:3 [ "pii" => "S0735109703009215" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surface proteoglycans as mediators in bacterial pathogens infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. García" 1 => "J. Merayo-Lloves" 2 => "C. Martin" 3 => "I. Alcalde" 4 => "L.M. Quirós" 5 => "F. Vazquez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fmicb.2016.00220" "Revista" => array:6 [ "tituloSerie" => "Front Microbiol" "fecha" => "2016" "volumen" => "7" "paginaInicial" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26941735" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109712012375" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Large surface of cultured human epithelium obtained on a dermal matrix based on live fibroblast-containing fibrin gels" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Meana" 1 => "J. Iglesias" 2 => "M. del Rio" 3 => "F. Larcher" 4 => "B. Madrigal" 5 => "M.F. Fresno" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0305-4179(98)00107-7" "Revista" => array:6 [ "tituloSerie" => "Burns" "fecha" => "1998" "volumen" => "24" "paginaInicial" => "621" "paginaFinal" => "630" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9882060" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhodamine B and 2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-<span class="elsevierStyleSmallCaps">d</span>-glucopyranose (F-GlcNAc) inhibit chondroitin/dermatan and keratan sulphate synthesis by different mechanisms in bovine chondrocytes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.L. Derrick-Roberts" 1 => "W. Marais" 2 => "S. Byers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ymgme.2012.04.002" "Revista" => array:6 [ "tituloSerie" => "Mol Genet Metab" "fecha" => "2012" "volumen" => "106" "paginaInicial" => "214" "paginaFinal" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22546219" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Xyloside priming of glycosaminoglycan biosynthesis and inhibition of proteoglycan assembly" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.A. Fritz" 1 => "J.D. Esko" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1385/1-59259-209-0:317" "Revista" => array:5 [ "tituloSerie" => "Methods Mol Biol" "fecha" => "2001" "volumen" => "171" "paginaInicial" => "317" "paginaFinal" => "323" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Piotrowska" 1 => "J. Jakóbkiewicz-Banecka" 2 => "S. Barańska" 3 => "A. Tylki-Szymańska" 4 => "B. Czartoryska" 5 => "A. Wegrzyn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ejhg.5201623" "Revista" => array:6 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2006" "volumen" => "14" "paginaInicial" => "846" "paginaFinal" => "852" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16670689" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of genistein on the synthesis and distribution of glycosaminoglycans/proteoglycans by two osteosarcoma cell lines depends on tyrosine kinase and the estrogen receptor density" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Nikitovic" 1 => "A.M. Tsatsakis" 2 => "N.K. Karamanos" 3 => "G.N. Tzanakakis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Anticancer Res" "fecha" => "2003" "volumen" => "23" "numero" => "1A" "paginaInicial" => "459" "paginaFinal" => "464" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12680249" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Widespread use of Lactobacillus OppA, a surface located protein, as an adhesin that recognises epithelial cell surface glycosaminoglycans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Martín" 1 => "S. Escobedo" 2 => "J.E. Suárez" 3 => "L.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 14 | 26 |
| 2024 October | 76 | 64 | 140 |
| 2024 September | 75 | 41 | 116 |
| 2024 August | 95 | 74 | 169 |
| 2024 July | 104 | 35 | 139 |
| 2024 June | 88 | 37 | 125 |
| 2024 May | 84 | 31 | 115 |
| 2024 April | 80 | 34 | 114 |
| 2024 March | 64 | 33 | 97 |
| 2024 February | 57 | 31 | 88 |
| 2024 January | 64 | 38 | 102 |
| 2023 December | 62 | 22 | 84 |
| 2023 November | 72 | 31 | 103 |
| 2023 October | 67 | 27 | 94 |
| 2023 September | 61 | 36 | 97 |
| 2023 August | 45 | 17 | 62 |
| 2023 July | 53 | 30 | 83 |
| 2023 June | 43 | 26 | 69 |
| 2023 May | 51 | 22 | 73 |
| 2023 April | 35 | 23 | 58 |
| 2023 March | 40 | 35 | 75 |
| 2023 February | 39 | 31 | 70 |
| 2023 January | 32 | 37 | 69 |
| 2022 December | 52 | 43 | 95 |
| 2022 November | 42 | 37 | 79 |
| 2022 October | 38 | 38 | 76 |
| 2022 September | 29 | 43 | 72 |
| 2022 August | 32 | 43 | 75 |
| 2022 July | 24 | 47 | 71 |
| 2022 June | 27 | 35 | 62 |
| 2022 May | 38 | 52 | 90 |
| 2022 April | 55 | 44 | 99 |
| 2022 March | 53 | 77 | 130 |
| 2022 February | 61 | 60 | 121 |
| 2022 January | 78 | 47 | 125 |
| 2021 December | 61 | 49 | 110 |
| 2021 November | 74 | 59 | 133 |
| 2021 October | 79 | 70 | 149 |
| 2021 September | 75 | 57 | 132 |
| 2021 August | 155 | 62 | 217 |
| 2021 July | 144 | 76 | 220 |
| 2021 June | 60 | 77 | 137 |
| 2021 May | 68 | 12 | 80 |
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