Biology subjects

Peschel, A.

Publications and source records attributed to Peschel, A..

16 recordsLinked to original sources

bioRxiv2026

A teichoic acid-like wall modification associated with immune suppression is socially regulated in Streptococcus pyogenes

Streptococcus pyogenes (Group A Streptococcus, GAS) is a human-restricted pathogen with a range of clinical manifestations and worldwide prevalence. The GAS Rgg2/Rgg3 quorum sensing (QS) system, a cell-to-cell communication network, modifies the cell surface resulting in increased lysozyme resistance, biofilm formation, and expression of the qim operon that is responsible for modulation of innate immune responses in macrophages. The operon encodes 10 genes with predicted homology to enzymes involved in bacterial cell surface-associated carbohydrate and teichoic acid biosynthesis pathways. Comparing extracts of GAS cell wall polysaccharides between wildtype and operon mutants determined that the QS-induced genes modify the S. pyogenes cell surface by adding a wall teichoic acid-like moiety of N-acetylglucosamine-linked ribitol (GlcNAc-Rbo). A fluorescently labeled phage receptor-binding protein, RBP-13-GFP, that recognizes GlcNAc-decorated ribitol phosphate repeats, bound to the GAS surface only when qim expression was induced. Deletion of the qim operon eliminated RBP-13-GFP binding, diminished bacterial colonization, and significantly attenuated GAS pathogenesis in a murine skin infection model. These findings indicate that GAS has evolved a strategy to evade innate immune response by presenting a previously unknown carbohydrate moiety upon quorum sensing. IMPORTANCEStreptococcus pyogenes is a major human pathogen, responsible for diverse clinical manifestations of both superficial and invasive infections and can lead to post-infection sequelae like rheumatic heart disease whose prevalence on a global scale rivals the most serious pathogens. Invasive S. pyogenes infections are currently on the rise worldwide, notably correlating with increasing pediatric cases of scarlet fever and enhancing the concern for long term complications. There is much that remains unknown about S. pyogenes virulence and pathogenicity, and studies focused on understanding basic systems regulating virulence factors could lead to better therapeutics and translational research. We show here one such example, where a bacterial communication system regulating a virulence mechanism relevant to in vivo infection confers the ability to alter the host innate immune response. We find that modifications to the cell wall arise when this virulence system is activated that has a direct role in host-pathogen interactions. Further research into this system could provide a mechanism for disruption and serve to treat S. pyogenes infection.

microbiology↗

bioRxiv2025

Genetic modification of intractable staphylococcal clones by heat-shock facilitated phage transduction

Increasing recognition of commensal bacteria as a requirement for microbiome integrity and pathogen exclusion puts urgency to the molecular characterization of commensal interactions. However, many commensals cannot be transformed with available methodology because of potent restriction barriers. We developed a new method for the introduction of plasmid DNA into otherwise intractable non-Staphylococcus aureus (NAS) staphylococci, important commensal members of human nose and skin microbiomes, by phage transduction. We demonstrate that a precise pulse of recipient bacteria with elevated temperatures prior to exposure to transducing phages renders NAS isolates effectively and transiently amenable to transduction. Transduction of NAS mutants lacking restriction-modification (RM) systems did not profit from a heat shock indicating that it is the transient deactivation of RM enzymes that permit transduction. Our method also facilitated the transduction of other Bacillota from the genera Bacillus and Listeria indicating that it will support research on different bacterial groups from diverse ecosystems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/647181v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@233348org.highwire.dtl.DTLVardef@fbf57corg.highwire.dtl.DTLVardef@1b1abadorg.highwire.dtl.DTLVardef@17e283f_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Probiotic Lactobacilli activate Formyl-Peptide Receptor 2

Changes in the composition of the human microbiota can negatively impact human health. Probiotic bacteria like many lactobacilli help prevent or repair dysbiosis but it is largely unclear which molecules of these bacteria mediate the probiotic effects. Given the extensive crosstalk between the immune system and microbiome members, we investigated whether lactobacilli activate the formyl-peptide receptor 2 (FPR2), a pattern recognition receptor that is expressed on the surface of intestinal epithelial cells and known to promote wound healing and immune homeostasis. Probiotic strains of Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus were isolated from probiotic compounds and sequenced. Calcium influx experiments in FPR1 or FPR2 overexpressing HL60 cells, and primary human neutrophils, along with pharmacological inhibition of FPR2, revealed that culture filtrates of the isolated lactobacilli strongly activate FPR2, promote killing of the methicillin resistant S. aureus USA300 and induce neutrophil chemotaxis. Pretreatment of culture filtrates with proteinase K reduced FPR2 activity, indicating that the FPR2 ligands are peptides. In silico analysis of the amphipathic properties of the signal peptides of lactic acid bacteria identified selected signal peptides of L. plantarum with the ability to predominantly activate FPR2 in vitro. Thereby, via targeted activation of FPR2, peptides released by some lactobacilli are likely to positively influence the outcome of inflammatory gut diseases and could be used to treat inflammatory diseases.

microbiology↗

bioRxiv2024

Systematic classification of phage receptor-binding proteins predicts surface glycopolymer structure in Staphylococcus pathogens

Wall teichoic acids (WTAs) are major surface polymers of staphylococcal pathogens and commensals, whose variable structure governs interaction with host receptors, immunoglobulins, and bacteriophages. The ribitol phosphate (RboP) WTA type contributes to virulence, for instance in Staphylococcus aureus, but we lack comprehensive knowledge of WTA types and cognate phages. We developed a computational pipeline to identify the receptor-binding proteins (RBPs) in 335 Staphylococcus phage genomes, yielding multiple distinct RBP clusters. Notably, many phages had two separate RBPs with in part different WTA preferences. RBP representatives differed in specificity for RboP WTA glycosylation types, recapitulating the specificity of the corresponding phage. Based on these results, we created a publicly available bioinformatic tool to predict phage host specificity based on RBP similarity. The RboP WTA specific {Phi}13-RBP also revealed that the presence of RboP WTA on non-aureus staphylococci is more common than previously thought. Our approach facilitates the characterization of opportunistic Staphylococcus pathogens according to WTA types, which has major implications for phage-mediated interspecies horizontal gene transfer and future phage therapies.

microbiology↗

bioRxiv2024

Siderophore piracy enables the nasal commensal Staphylococcus lugdunensis to antagonize the pathogen Staphylococcus aureus

Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes - beneficial commensal bacteria can often prevent the persistence of certain pathogens - using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and how S. lugdunensis carriage could be promoted to enhance its S. aureus-eliminating capacity. We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supporting commensals, and on the capacity of S. lugdunensis to import siderophores. These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

microbiology↗

bioRxiv2023

Wall teichoic acid substitution with glucose governs phage susceptibility of Staphylococcus epidermidis

The species- and clone-specific susceptibility of Staphylococcus cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycocodes of phage-WTA interaction in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new S. epidermidis WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as {Phi}E72 but enables binding of otherwise unbound podoviruses. S. epidermidis glycerolphosphate WTA was found to be modified with glucose in a tagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. {Phi}E72 transduced several other CoNS species encoding TagE homologs suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits inter-species horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcus interaction and of horizontal gene transfer and it will help in the design of anti-staphylococcal phage therapies. ImportancePhages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genus Staphylococcus bind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative Staphylococcus (CoNS) species has remained unknown. We describe that S. epidermidis glycosylates its WTA backbone with glucose and we identify a cluster of three genes, responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus {Phi}E72 suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.

microbiology↗

bioRxiv2023

The capsular polysaccharide obstructs wall teichoic acid functions in Staphylococcus aureus

BackgroundThe cell envelope of Staphylococcus aureus contains two major secondary cell wall glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Both the CP and the WTA are attached to the cell wall and play distinct roles in S. aureus colonization, pathogenesis, and bacterial evasion of host immune defenses. ObjectiveWe aimed to investigate whether CP interferes with WTA-mediated properties. MethodsStrains with natural heterogeneous expression of CP, strains with homogeneous high CP expression and CP-deficient strains were compared to WTA deficient controls regarding WTA dependent phage binding, cell adhesion, IgG deposition, and virulence in vivo. ResultsWTA-mediated phage adsorption, specific antibody deposition and cell adhesion were negatively correlated with CP expression. WTA, but not CP, enhanced the bacterial burden in a mouse abscess model, while CP overexpression resulted in intermediate virulence in vivo. ConclusionsCP protects the bacteria from WTA-dependent opsonization and phage binding. This protection comes at the cost of diminished adhesion to host cells. The highly complex regulation and mostly heterogeneous expression of CP has probably evolved to ensure the survival and optimal physiological adaptation of the bacterial population as a whole.

microbiology↗

bioRxiv2023

Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus

Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was more common in blood and nose isolates than in skin strains, suggesting a particularly important role of Lip2 for skin colonization. Accordingly, in a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid - a human-specific AFA - in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth. Our data support a model in which S. aureus exploits and/or exacerbates lipid disorders to colonize otherwise inhospitable niches.

microbiology↗

bioRxiv2023

Cross-species communication via agr controls phage susceptibility in Staphylococcus aureus

Bacteria and their viruses (phages) use quorum sensing (QS) systems to coordinate group behavior. In Staphylococcus aureus, QS plays a critical role in the transition from colonization to infection and involves the accumulation of auto-inducing peptides (AIPs). Humans and animals are also colonized by non-aureus staphylococci (NAS) that produce AIPs, many of which inhibit S. aureus QS. We found that QS induction is necessary for S. aureus susceptibility to the lytic phage, Stab20 and that in mixed communities with NAS producing inhibitory AIPs, S. aureus is protected from phage infection. The primary phage receptors in S. aureus are wall teichoic acids (WTA) substituted with - and/or {beta}-linked N- acetylglucosamine (GlcNAc). We show that QS induction reduces -GlcNAc substitutions and enables Stab20 infection through binding to {beta}-glycosylated WTA. However, in the presence of inhibitory AIPs or during co-culture with NAS, QS induction and Stab20 infection are impeded. Our results highlight how cross-species communication can significantly impact bacterial susceptibility to phages and may explain occasional failures observed when phages are used as antimicrobials in for example phage therapy.

microbiology↗

bioRxiv2022

Targeting of the human nasal microbiota by secretory IgA antibodies

The human nasal microbiome is critical for health and disease, since it is associated with the occurrence of respiratory disorders and hosting of opportunistic pathogens. The host therefore protects this vulnerable mucosal barrier from infection and maintains homeostasis of the microbiota through various mechanisms, including the production of secretory IgA (sIgA) antibodies. However, we currently lack a comprehensive understanding of how sIgA affects the nasal microbiota. Through IgA-seq analysis of nasal microbiome samples and sIgA deposition experiments using nasal sIgA from healthy volunteers, we identified which bacterial genera and species are targeted by sIgA on the level of the individual host. We observed that the amount of sIgA secreted into the nasal mucosa by the host varied substantially and was negatively correlated with the bacterial density. The interaction between mucosal sIgA antibodies and the nasal microbiome was highly individual, and was not dependent on the microbiome composition, or the age or gender of the host. Importantly, we showed that for the clinically relevant opportunistic pathogen S. aureus, sIgA reactivity was in part the result of epitope-independent interaction of sIgA with the antibody binding protein SpA through binding of sIgA Fab regions. This study thereby offers a first comprehensive insight of targeting of nasal microbiota by sIgA antibodies, which may help to better understand the shaping and homeostasis of the nasal microbiome by the host and offer new targets for intervention in disease-associated microbiota.

microbiology↗

bioRxiv2022

Horizontal transfer of bacteriocin biosynthesis genes requires metabolic adaptation to improve compound production and cellular fitness

Biosynthetic gene clusters (BGCs) encoding the production of bacteriocins are widespread amongst bacterial isolates and are important genetic determinants of competitive fitness within a given habitat. Staphylococci produce a tremendous diversity of compounds and the corresponding BGCs are frequently associated with mobile genetic elements, suggesting gain and loss of biosynthetic capacity. Pharmaceutical biology has shown that compound production in heterologous hosts is often challenging and many BGC recipients produce initially low compound amounts or show reduced growth rates. To assess whether transfer of BGCs between closely related S. aureus strains can be instantly effective or requires elaborate metabolic adaptation, we investigated the intra species transfer of a BGC encoding the ribosomally synthesized and post-translationally modified peptide (RiPP) micrococcin P1 (MP1). We found that acquisition of the BGC by S. aureus RN4220 enabled immediate MP1 production but also imposed a metabolic burden, which was relieved after prolonged cultivation by adaptive mutation. We used a multiomics approach to study this phenomenon and found adaptive evolution to select for strains with increased activity of the tricarboxylic acid cycle (TCA), which enhanced metabolic fitness and levels of compound production. Metabolome analysis revealed increases of central metabolites including citrate and -ketoglutarate in the adapted strain, suggesting metabolic adaptation to overcome the BGC-associated growth defects. Our results indicate that BCG acquisition requires genetic and metabolic predispositions allowing the integration of bacteriocin production into the cellular metabolism. Inappropriate metabolic characteristics of recipients can entail physiological burdens, negatively impacting the competitive fitness of recipients within natural bacterial communities. ImportanceHuman microbiomes are critically associated with human health and disease. Importantly, pathogenic bacteria can hide in human associated communities and can cause disease when the composition of the community becomes dysbalanced. Bacteriocin producing commensals are able to displace pathogens from microbial communities, suggesting that their targeted introduction in human microbiomes might prevent pathogen colonisation and infection. However, in view of future probiotic approaches, strains are needed that produce high levels of bioactive compounds and retain cellular fitness within mixed bacterial communities. Our work offers insights into the metabolic burdens associated with the production of the bacteriocin micrococcin P1 and highlights evolutionary strategies that increase cellular fitness in the context of production. Most likely metabolic adaptations are broadly relevant for bacteriocin producers and need to be considered for the future development of effective microbiome editing strategies.

microbiology↗

bioRxiv2022

Prokaryotic phospholipid translocation by ubiquitous PplT domain proteins

Flippase proteins exchanging phospholipids between the cytoplasmic membrane leaflets have been identified in Eukaryotes but remained largely unknown in Prokaryotes. Only MprF proteins that synthesize aminoacyl phospholipids in some bacteria have been found to contain a domain that translocates the produced lipids. We show here that this domain, which we named prokaryotic phospholipid translocator (PplT), is widespread in Bacteria and Archaea, encoded as a separate protein or fused to different types of enzymes. We also demonstrate that the Escherichia coli PplT protein interacts with many phospholipid-synthetic enzymes and deletion of pplT impaired bacterial growth, which supports its potential role in membrane lipid metabolism. PplT domain proteins may be general prokaryotic lipid flippases with critical roles in cellular homeostasis.

microbiology↗

bioRxiv2020

Decoding and blocking the bacterial lipid flippase MprF yields a novel anti-virulence strategy

The pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. MprF is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to both, human antimicrobials and antibiotics and support the clearance of staphylococcal infections with minimal selection pressure, we developed MprF-targeting monoclonal antibodies, which bound and blocked the MprF flippase subunit. Antibody M-C7.1 targeted a specific loop in the flippase domain that proved to be exposed at both sides of the bacterial membrane, thereby enhancing the mechanistic understanding into bacterial lipid translocation. M-C7.1 rendered MRSA susceptible to host antimicrobial peptides and antibiotics such as daptomycin. Moreover, it impaired MRSA survival in human phagocytes, which recommends MprF inhibitors for new anti-MRSA approaches. MprF-directed monoclonal antibodies provide a proof of concept for development of precisely targeted anti-virulence approaches, which block bacterial antimicrobial resistance mechanisms.

microbiology↗

bioRxiv2020

The impact of Staphylococcus aureus cell wall glycosylation on langerin recognition and Langerhans cell activation

Staphylococcus aureus is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to S. aureus invasion and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, sense S. aureus through their pattern-recognition receptor langerin, triggering a pro-inflammatory response. Langerin specifically recognizes the {beta}-1,4-linked N-acetylglucosamine ({beta}-GlcNAc) modification, which requires the glycosyltransferase TarS, on the cell wall glycopolymer Wall Teichoic Acid (WTA). Recently, an alternative WTA glycosyltransferase, TarP, was identified in methicillin-resistant S. aureus strains belonging to clonal complexes (CC) 5 and CC398. TarP also modifies WTA with {beta}-GlcNAc but at the C-3 position of the WTA ribitol phosphate (RboP) subunit. Here, we aimed to unravel the impact of {beta}-GlcNAc linkage position for langerin binding and LC activation. In addition, we performed structure-binding studies using a small panel of unique chemically-synthesized WTA molecules to assess langerin-WTA binding requirements. Using FITC-labeled recombinant human langerin and genetically-modified S. aureus strains, we observed that langerin similarly recognized bacteria that produce either TarS- or TarP-modified WTA. Furthermore, using chemically-synthesized WTA, representative of the different S. aureus WTA glycosylation patterns, established that {beta}-GlcNAc is sufficient to confer langerin binding. Functionally, tarP-expressing S. aureus induce increased cytokine production and maturation of in vitro-generated LCs compared to tarSexpressing S. aureus. Overall, our data suggest that LCs are able to sense all {beta}-GlcNAc-WTA producing S. aureus strains, likely performing an important role as first responders upon S. aureus skin invasion.

microbiology↗

bioRxiv2020

Phosphoglycerol-type wall- and lipoteichoic acids are enantiomeric polymers differentially cleaved by the stereospecific glycerophosphodiesterase GlpQ

The cell envelope of Gram-positive bacteria generally comprises two types of polyanionic polymers, either linked to peptidoglycan, wall teichoic acids (WTA), or to membrane glycolipids, lipoteichoic acids (LTA). In some bacteria, including Bacillus subtilis strain 168, WTA and LTA both are glycerolphosphate polymers, yet are synthesized by different pathways and have distinct, although not entirely understood morphogenetic functions during cell elongation and division. We show here that the exo-lytic sn-glycerol-3-phosphodiesterase GlpQ can discriminate between B. subtilis WTA and LTA polymers. GlpQ completely degrades WTA, lacking modifications at the glycerol residues, by sequentially removing glycerolphosphates from the free end of the polymer up to the peptidoglycan linker. In contrast, GlpQ is unable to cleave unmodified LTA. LTA can only be hydrolyzed by GlpQ when the polymer is partially pre-cleaved, thereby allowing GlpQ to get access to the end of the polymer that is usually protected by a connection to the lipid anchor. This indicates that WTA and LTA are enantiomeric polymers: WTA is made of sn-glycerol-3-phosphate and LTA is made of sn-glycerol-1-phosphate. Differences in stereochemistry between WTA and LTA were assumed based on differences in biosynthesis precursors and chemical degradation products, but so far had not been demonstrated directly by differential, enantioselective cleavage of isolated polymers. The discriminative stereochemistry impacts the dissimilar physiological and immunogenic properties of WTA and LTA and enables independent degradation of the polymers, while appearing in the same location; e.g. under phosphate limitation, B. subtilis 168 specifically hydrolyzes WTA and synthesizes phosphate-free teichuronic acids in exchange.

microbiology↗

bioRxiv2017

Wall teichoic acid is a pathogen-associated molecular pattern of Staphylococcus aureus that is recognized by langerin (CD207) on skin Langerhans cells

Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The underlying molecular mechanisms of the association between S. aureus and skin inflammation are poorly understood. Here, we demonstrate that human LCs directly interact with S. aureus through the pattern-recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved {beta}-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of Th1-and Th17-polarizing cytokines that are produced by in vitro generated LCs. Finally, in a murine epicutaneous infection model, S. aureus induced a more pronounced influx of inflammatory cells and pro-inflammatory cytokine transcripts in skin of human langerin transgenic mice compared to wild-type mice. Our findings provide molecular insight into the unique pro-inflammatory capacities of S. aureus in relation to inflammatory skin disease.

microbiology↗