scholarly journals Chlamydia trachomatis: the Persistent Pathogen

2017 ◽  
Vol 24 (10) ◽  
Author(s):  
Steven S. Witkin ◽  
Evelyn Minis ◽  
Aikaterini Athanasiou ◽  
Julie Leizer ◽  
Iara M. Linhares
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Productive Infection ◽  
Host Immune System ◽  
Treatment Protocols ◽  
Content Type ◽  
Reticulate Body ◽  
Membrane Components ◽  
Infectious Form ◽  
Human Hsp60

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. C. trachomatis has evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form, C. trachomatis ceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood that C. trachomatis will avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.

scholarly journals Selected Immunological Mediators and Cervical Microbial Signatures in Women with Chlamydia trachomatis Infection

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Simone Filardo ◽  
Marisa Di Pietro ◽  
Giulia Tranquilli ◽  
Maria Agnese Latino ◽  
Nadia Recine ◽  
...  
Keyword(s):  
Immune System ◽  
Chlamydia Trachomatis ◽  
Host Immune System ◽  
Complex Interplay ◽  
Content Type ◽  
Immune Mediators ◽  
Potential Biomarker ◽  
Ifn Γ ◽  
Low Levels ◽  
Female Genital

ABSTRACT In the female genital ecosystem, the complex interplay between the host immune system and the resident microflora protects against urogenital pathogens, like Chlamydia trachomatis. C. trachomatis is responsible for urethritis and cervicitis; however, most chlamydial infections are asymptomatic and, thus, not treated, potentially leading to severe reproductive sequelae. Here we investigated the interaction between the levels of selected immune mediators and the community state types of the cervical microbiota in C. trachomatis-infected women. Cervical samples from 42 C. trachomatis-positive women and 103 matched healthy controls were analyzed through the metagenomic analysis of the hypervariable region v4 of the 16S rRNA gene and the determination of lactoferrin, interleukin 1α (IL-1α), IL-6, alpha interferon (IFN-α), IFN-β, and IFN-γ by ELISA. Overall, C. trachomatis infection was significantly associated with a microbiota dominated by anaerobic bacteria (P = 0.000002). In addition, a network of Gardnerella vaginalis, Prevotella amnii, Prevotella buccalis, Prevotella timonensis, Aerococcus christensenii, and Variovorax guangxiensis has been identified as a potential biomarker of C. trachomatis infection through multiple statistical approaches. Again, chlamydial infection was significantly correlated with an increased production of lactoferrin, IL-6, IL-1α, IFN-α, and IFN-β (P < 0.05), whereas very low levels of IFN-γ were observed in C. trachomatis-infected women, levels similar to those detected in healthy women. Our findings show a distinctive signature of C. trachomatis genital infection, characterized by a specific bacterial network, constituted by anaerobes, as well as by increased levels of lactoferrin and proinflammatory cytokines (IL-1α, IL-6, IFN-α, and IFN-β), accompanied by low levels of IFN-γ. IMPORTANCE To our knowledge, this is the first study that investigated the association of C. trachomatis with the cervical levels of lactoferrin and selected inflammatory mediators and their correlation with the different community state types characterizing the female genital ecosystem. C. trachomatis, known as the leading cause of bacterial sexually transmitted diseases, continues to be an important public health problem worldwide for its increasing incidence and the risk of developing severe reproductive sequelae, like pelvic inflammatory disease and infertility. Specifically, C. trachomatis tend to persist in the female genital tract, leading to a chronic inflammatory state characterized by increased production of immune mediators responsible for tissue damage. Therefore, our study may help to broaden the knowledge on the complex interplay between the female genital microbiota and the host immune system in response to C. trachomatis infection.

scholarly journals Transcriptional Profiling of Human Epithelial Cells Infected with Plasmid-Bearing and Plasmid-Deficient Chlamydia trachomatis

2014 ◽  
Vol 83 (2) ◽  
pp. 534-543 ◽  
Author(s):  
Stephen F. Porcella ◽  
John H. Carlson ◽  
Daniel E. Sturdevant ◽  
Gail L. Sturdevant ◽  
Kishore Kanakabandi ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Transcriptional Profiling ◽  
Colony Stimulating Factor ◽  
Content Type ◽  
Human Epithelial Cells ◽  
Infected Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Chlamydia trachomatisis an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected withC. trachomatisplasmid-bearing (A2497) and plasmid-deficient (A2497P−) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1α, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P−-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis.

scholarly journals Inhibition of Indoleamine 2,3-Dioxygenase Activity by Levo-1-Methyl Tryptophan Blocks Gamma Interferon-Induced Chlamydia trachomatis Persistence in Human Epithelial Cells

2011 ◽  
Vol 79 (11) ◽  
pp. 4425-4437 ◽  
Author(s):  
Joyce A. Ibana ◽  
Robert J. Belland ◽  
Arnold H. Zea ◽  
Danny J. Schust ◽  
Takeshi Nagamatsu ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Gamma Interferon ◽  
Developmental Cycle ◽  
Tryptophan Depletion ◽  
Content Type ◽  
Indoleamine 2,3 Dioxygenase ◽  
Human Epithelial Cells ◽  
Ifn Γ

ABSTRACTGamma interferon (IFN-γ) induces expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO1) in human epithelial cells, the permissive cells for the obligate intracellular bacteriumChlamydia trachomatis. IDO1 depletes tryptophan by catabolizing it to kynurenine with consequences forC. trachomatis, which is a tryptophan auxotroph.In vitrostudies reveal that tryptophan depletion can result in the formation of persistent (viable but noncultivable) chlamydial forms. Here, we tested the effects of the IDO1 inhibitor, levo-1-methyl-tryptophan (L-1MT), on IFN-γ-inducedC. trachomatispersistence. We found that addition of 0.2 mM L-1MT to IFN-γ-exposed infected HeLa cell cultures restricted IDO1 activity at the mid-stage (20 h postinfection [hpi]) of the chlamydial developmental cycle. This delayed tryptophan depletion until the late stage (38 hpi) of the cycle. Parallel morphological and gene expression studies indicated a consequence of the delay was a block in the induction ofC. trachomatispersistence by IFN-γ. Furthermore, L-1MT addition allowedC. trachomatisto undergo secondary differentiation, albeit with limited productive multiplication of the bacterium. IFN-γ-induced persistent infections in epithelial cells have been previously reported to be more resistant to doxycycline than normal productive infectionsin vitro. Pertinent to this observation, we found that L-1MT significantly improved the efficacy of doxycycline in clearing persistentC. trachomatisforms. It has been postulated that persistent forms ofC. trachomatismay contribute to chronic chlamydial disease. Our findings suggest that IDO1 inhibitors such as L-1MT might provide a novel means to investigate, and potentially target, persistent chlamydial forms, particularly in conjunction with conventional therapeutics.

scholarly journals Enterohemorrhagic Escherichia coli O157:H7 Shiga Toxins Inhibit Gamma Interferon-Mediated Cellular Activation

2012 ◽  
Vol 80 (7) ◽  
pp. 2307-2315 ◽  
Author(s):  
Nathan K. Ho ◽  
Juan C. Ossa ◽  
Uma Silphaduang ◽  
Roger Johnson ◽  
Kathene C. Johnson-Henry ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Cell Activation ◽  
Gamma Interferon ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Immune System ◽  
Content Type ◽  
Shiga Toxins ◽  
Ifn Γ

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) serotype O157:H7 is a food-borne pathogen that causes significant morbidity and mortality in developing and industrialized nations. EHEC infection of host epithelial cells is capable of inhibiting the gamma interferon (IFN-γ) proinflammatory pathway through the inhibition of Stat-1 phosphorylation, which is important for host defense against microbial pathogens. The aim of this study was to determine the bacterial factors involved in the inhibition of Stat-1 tyrosine phosphorylation. Human HEp-2 and Caco-2 epithelial cells were challenged directly with either EHEC or bacterial culture supernatants and stimulated with IFN-γ, and then the protein extracts were analyzed by immunoblotting. The data showed that IFN-γ-mediated Stat-1 tyrosine phosphorylation was inhibited by EHEC secreted proteins. Using two-dimensional difference gel electrophoresis, EHEC Shiga toxins were identified as candidate inhibitory factors. EHEC Shiga toxin mutants were then generated and complemented intrans, and mutant culture supernatant was supplemented with purified Stx to confirm their ability to subvert IFN-γ-mediated cell activation. We conclude that while other factors are likely involved in the suppression of IFN-γ-mediated Stat-1 tyrosine phosphorylation,E. coli-derived Shiga toxins represent a novel mechanism by which EHEC evades the host immune system.

scholarly journals Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent onChlamydia trachomatisStrain Type and Likely Influence Disease Outcomes

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Amber Leah Jolly ◽  
Sameeha Rau ◽  
Anmol K. Chadha ◽  
Ekhlas Ahmed Abdulraheem ◽  
Deborah Dean
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Genital Tract ◽  
Inflammatory Responses ◽  
Infection Rates ◽  
Progeny Production ◽  
Content Type ◽  
Disease Outcomes ◽  
Primary Fibroblasts ◽  
Strain Type

ABSTRACTChlamydia trachomatisocular strains cause a blinding disease known as trachoma. These strains rarely cause urogenital infections and are not found in the upper genital tract or rectum. Urogenital strains are responsible for a self-limited conjunctivitis and the sequelae of infertility, ectopic pregnancy, and hemorrhagic proctitis. However, the differential cellular responses that drive these clinically observed disease outcomes are not completely understood. Primary conjunctival, endocervical, and endometrial epithelial and stromal fibroblast cells, HeLa229 cells, and immortalized conjunctival epithelial (HCjE) cells were infected with the ocular A/Har-13 (A) and Ba/Apache-2 (Ba) strains and urogenital D/UW-3 (D) and E/Bour (E) strains. Infection rates, progeny production, and cytokine/chemokine secretion levels were evaluated in comparison with those in uninfected cells. All strain types infected all cell types with similar levels of efficacy and development. However, progeny production levels differed among primary cells: Ba produced significantly more progeny than E in endocervical and endometrial fibroblasts, while A progeny were less abundant than E progeny.C.trachomatisinfection of primary epithelial cells elicited an increase in pro- and anti-inflammatory mediators compared to levels in uninfected cells, but there were no significant differences by strain type. In contrast, for primary fibroblasts, ocular strains elicited significant increases in the pro- and anti-inflammatory mediators macrophage inflammatory protein (MIP)-1β, thymus- and activation-regulated chemokine (TARC), interleukin (IL)-2, IL-12p70, and interferon gamma-induced protein 10 (IP-10) compared to levels in urogenital strains, while urogenital strains elicited a distinct and significant increase in the proinflammatory mediators IL-1α, IL-1β, IL-8, gamma interferon (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Our data indicate that primary fibroblasts, not epithelial cells, drive host inflammatory responses that are dependent on strain type and likely influence disease outcomes, establishing their importance as a novel model for studies ofC. trachomatisdisease pathogenesis.IMPORTANCEChlamydia trachomatisis a human pathogen and the leading cause of preventable blindness and sexually transmitted diseases in the world. CertainC. trachomatisstrains cause ocular disease, while others cause upper genital tract pathology. However, little is known about the cellular or immunologic basis for these differences. Here, we compared the abilities of the strain types to infect, replicate, and initiate an immune response in primary human ocular and urogenital epithelial cells, as well as in fibroblasts from the underlying stroma. While there were no significant differences in infection rates or intracellular growth for any strain in any cell type, proinflammatory responses were driven not by the epithelial cells but by fibroblasts and were distinct between ocular and urogenital strains. Our findings suggest that primary fibroblasts are a novel and more appropriate model for studies of immune responses that will expand our understanding of the differential pathological disease outcomes caused by variousC. trachomatisstrain types.

scholarly journals Reversible Inhibition of Chlamydia trachomatis Infection in Epithelial Cells Due to Stimulation of P2X4Receptors

2012 ◽  
Vol 80 (12) ◽  
pp. 4232-4238 ◽  
Author(s):  
Matthew A. Pettengill ◽  
Camila Marques-da-Silva ◽  
Maria Luisa Avila ◽  
Suellen d'Arc dos Santos Oliveira ◽  
Verissa W. Lam ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Bacterial Infections ◽  
Degradation Products ◽  
Microbial Pathogens ◽  
Content Type ◽  
Chlamydia Trachomatis Infection ◽  
Extracellular Milieu ◽  
Infected Cells ◽  
Stimulation Of

ABSTRACTBacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly bacterial infection through ligation of P2X7receptors. We show here that the proinflammatory mediator, ATP, is released fromChlamydia trachomatis-infected epithelial cells. Moreover, further stimulation of the infected cells with micromolar extracellular ADP or ATP significantly impairs the growth of the bacteria, with a profile characteristic of the involvement of P2X4receptors. A specific role for P2X4was confirmed using cells overexpressing P2X4. The chlamydiae remain viable and return to normal growth kinetics after removal of the extracellular stimulus, similar to responses previously described for persistence of chlamydial infection.

scholarly journals Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages

2013 ◽  
Vol 81 (8) ◽  
pp. 3045-3054 ◽  
Author(s):  
K. A. Fields ◽  
R. McCormack ◽  
L. R. de Armas ◽  
E. R. Podack
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Hela Cells ◽  
Ectopic Expression ◽  
Host Cells ◽  
Content Type ◽  
Obligate Intracellular ◽  
Novel Host ◽  
Defense Protein ◽  
Resistance Protein

ABSTRACTChlamydia trachomatisis a Gram-negative obligate intracellular bacterium that preferentially infects epithelial cells. Professional phagocytes provideC. trachomatisonly a limited ability to survive and are proficient killers of chlamydiae. We present evidence herein that identifies a novel host defense protein, perforin-2, that plays a significant role in the eradication ofC. trachomatisduring the infection of macrophages. Knockdown of perforin-2 in macrophages did not alter the invasion of host cells but did result in chlamydial growth that closely mirrored that detected in HeLa cells.C trachomatisL2, serovar B, and serovar D andC. muridarumwere all equally susceptible to perforin-2-mediated killing. Interestingly, induction of perforin-2 expression in epithelial cells is blocked during productive chlamydial growth, thereby protecting chlamydiae from bactericidal attack. Ectopic expression of perforin-2 in HeLa cells, however, does result in killing. Overall, our data implicate a new innate resistance protein in the control of chlamydial infection and may help explain why the macrophage environment is hostile to chlamydial growth.

scholarly journals Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis

2017 ◽  
Vol 85 (7) ◽  
Author(s):  
Chunfu Yang ◽  
William M. Whitmire ◽  
Gail L. Sturdevant ◽  
Kevin Bock ◽  
Ian Moore ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Genital Tract ◽  
Plasma Cells ◽  
T Cell Response ◽  
Similar Species ◽  
Content Type ◽  
Chlamydia Muridarum

ABSTRACT We studied infection and immunity of hysterectomized mice infected with Chlamydia muridarum and Chlamydia trachomatis to determine if there were differences between these species in their ability to infect vaginal squamous epithelial cells in vivo independently of proximal upper genital tract tissues. We found that C. muridarum readily colonized and infected vaginal squamous epithelial cells, whereas C. trachomatis did not. Primary infection of the vaginal epithelium with C. muridarum produced infections of a duration longer than that reported for normal mice. Infection resulted in an inflammatory response in the vagina characterized by neutrophils and infiltrating submucosal plasma cells consisting primarily of T cells. Despite the delayed clearance, rechallenged C. muridarum-infected mice were highly immune. Mice vaginally infected with C. muridarum produced serum and vaginal wash antibodies and an antigen-specific gamma interferon-dominated Th1-biased T cell response. By comparison, mice vaginally infected with C. trachomatis exhibited transient low-burden infections, produced no detectable tissue inflammatory response, and failed to seroconvert. We discuss how these marked differences in the biology of vaginal infection between these otherwise genetically similar species are possibly linked to pathogen-specific virulence genes and how they may influence pathology and immunity in the upper genital tract.

scholarly journals Toll-Like Receptor 2-Dependent Activity of Native Major Outer Membrane Protein Proteosomes of Chlamydia trachomatis

2012 ◽  
Vol 81 (1) ◽  
pp. 303-310 ◽  
Author(s):  
Paola Massari ◽  
Deana N. Toussi ◽  
Delia F. Tifrea ◽  
Luis M. de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Host Cell ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Major Outer Membrane Protein ◽  
Host Cells ◽  
Content Type

Chlamydia trachomatisis the most common sexually transmitted bacterial pathogen and the etiologic agent of blinding trachoma. Intracellular signaling pathways leading to host cell inflammation and innate immunity toChlamydiainclude those mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization domain 1 (Nod1) protein. In epithelial cells, TLR-dependent signaling contributes to local immune responses via induction of inflammatory mediators. There is evidence that TLR3, TLR4, and, particularly, TLR2 are critical forChlamydia-mediated host cell activation and pathology. Despite the importance of TLR2, major chlamydial TLR2 antigens have not been identified so far. Numerous bacterial porins are known TLR2 agonists, i.e., porins fromNeisseriae,Shigella,Salmonella,Haemophilus influenzae, andFusobacterium nucleatum, which share structural and functional similarities with the chlamydial major outer membrane protein (MOMP), a strong antigen candidate for a potential vaccine againstC. trachomatis. We describe the ability of purified, detergent-free MOMP to signal via TLR2in vitroin TLR-overexpressing cells and TLR2-competent human reproductive tract epithelial cell lines. Using MOMP formed in pure protein micelles (proteosomes), we show the induction of TLR2-dependent interleukin-8 (IL-8) and IL-6 secretionin vitro, the involvement of TLR1 as a TLR2 coreceptor, and the activation of both NF-κB and mitogen-activated protein (MAP) kinase intracellular pathways. Interestingly, MOMP proteosomes induce cytokine secretion in endocervical epithelial cells (End/E6E7) but not in urethral epithelial cells (THUECs). A detailed understanding of the TLR2-dependent molecular mechanisms that characterize the effect of MOMP proteosomes on host cells may provide new insights for its successful development as an immunotherapeutic target againstChlamydia.

scholarly journals Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

2015 ◽  
Vol 83 (7) ◽  
pp. 2614-2626 ◽  
Author(s):  
Rohitashw Kumar ◽  
Darpan Saraswat ◽  
Swetha Tati ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Oral Candidiasis ◽  
Oral Microbiome ◽  
Proteinase Activity ◽  
Adhesion Properties ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Cell Cell

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually withC. albicanscells overexpressing Sap6 (SAP6OE and a Δsap8strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6strain was attenuated. These hypervirulent strains had highly aggregative colony structurein vitroand higher secreted proteinase activity; however, the levels of proteinase activity ofC. albicansSaps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6OE and Δsap8cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increasedC. albicansadhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

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