Psoriasin (S100A7) is a major Escherichia coli-cidal factor of the female genital tract

Mildner, Michael; Stichenwirth, Martin; Abtin, Arby; Eckhart, Leopold; Sam, Christine; Gläser, Regine; Jm, Schröder; Gmeiner, Ramona; Mlitz, Veronika; Pammer, Johannes; Geusau, Alexandra; Tschachler, Erwin

doi:10.1038/mi.2010.37

Cited by 45 publications

(41 citation statements)

References 31 publications

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“…However, in vitro studies have shown that S100A7 has strong anti-Escherichia coli activity 38 and is expressed by epithelial cells when they are exposed to microbial products. 12 Furthermore, histones and RPS27A are known to have pivotal functions in the innate immune system.…”

Section: Discussionmentioning

confidence: 99%

Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier

et al. 2016

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Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV. Cervicovaginal inflammation and other changes to the mucosal barrier are thought to have important roles but human data are scarce. We compared the human cervicovaginal proteome by mass spectrometry of 50 Rwandan female sex workers who had previously been clustered into four VMB groups using a 16S phylogenetic microarray; in order of increasing bacterial diversity: Lactobacillus crispatus-dominated VMB (group 1), Lactobacillus iners-dominated VMB (group 2), moderate dysbiosis (group 3), and severe dysbiosis (group 4). We compared relative protein abundances among these VMB groups using targeted (abundance of pre-defined mucosal barrier proteins) and untargeted (differentially abundant proteins among all human proteins identified) approaches. With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organizing proteins; decreasing keratins and cornified envelope proteins), increasing lactate dehydrogenase A/B as markers of cell death, increasing proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing proinflammatory cytokines, and decreasing immunoglobulins immunoglobulin G1/2. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier.

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Section: Discussionmentioning

confidence: 99%

Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier

et al. 2016

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“…oxS100A7 is highly abundant on healthy human skin and several mucosal surfaces (11)(12)(13). Its antibacterial activity is Zn 2+ -sensitive, acting via a histidinecoordinated low-affinity Zn 2+ -binding site (14).…”

Section: Significancementioning

confidence: 99%

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

Hein

Takahashi

Tsumori

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn 2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn 2+ -chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn 2+ -chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cellpenetrating Zn 2+ -chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.antifungal | innate immunity | epithelial defense | psoriasin | S100A7

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“…But the changes in the culture were not as impressive as in the native urine of the treated women. The locally applied lactic acid gel can also disturb the E.coli life cycle indirectly through changes of the vaginal environment [8], local innate immunity [9] or shift in the composition of the vaginal microbiota [10,11]. Filamentous transformation of E.coli was also reported as part of the life cycle of uropathogenic E.coli to subvert innate defenses of the host [12].…”

Section: Discussionmentioning

confidence: 98%

Positive effects of local therapy with a vaginal lactic acid gel on dysuria and E.coli bacteriuria question our current views on recurrent cystitis

Swidsinski

Loening‐Baucke

Mendling

et al. 2012

Arch Gynecol Obstet

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Objective We tested the effect of vaginally applied lactic acid gel on symptoms and bacteriuria in acutely exacerbated recurrent Eschericia coli cystitis. Methods Carnoy fixed samples of the morning urine from 20 women with a history of recurrent E.coli cystitis were prospectively investigated for bacteriuria using fluorescence in situ hybridization (FISH). Results In 11/20 women with acute cystitis, the symptoms and bacteriuria were regressive with lactic acid gel treatment, without the need for antibiotic treatment. The complete regression of symptoms took between 1 week (7 women) and 4 weeks (4 women). In parallel with this regression, the microscopic shape of E.coli bacteria in these women changed from short rods to long curly filaments starting within the first days of therapy. The filamentous transformation affected 100% of the E.coli population in six women and at least 50% of E.coli population in five women and was not observed in urine samples from untreated women or in women without clinical response to lactic acid gel. This could not happen if the bladder was the origin of the infection. Conclusions A number of recurrent and probably acute cystitis is a local vagino-urethritis caused by an adhesive invasive E.coli biofilm of the vaginal surface.

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Psoriasin (S100A7) is a major Escherichia coli-cidal factor of the female genital tract

Cited by 45 publications

References 31 publications

Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier

Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

Positive effects of local therapy with a vaginal lactic acid gel on dysuria and E.coli bacteriuria question our current views on recurrent cystitis

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