The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy.

Background: 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 invasion and persistence of such pathogens by using molecular strategies that are only superficially understood.

Stress Response to Bicarbonate Depletion.

Bicarbonate and CO are essential substrates for carboxylation reactions in bacterial central metabolism. In , the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. An deletion mutant can hardly grow in ambient air.

The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides.

Unlabelled: Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of . Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of within minutes due to protonophore activity.

Antimicrobial Evaluation of Two Polycyclic Polyprenylated Acylphloroglucinol Compounds: PPAP23 and PPAP53.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties.

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.

The Capsular Polysaccharide Obstructs Wall Teichoic Acid Functions in Staphylococcus aureus.

Background: The cell envelope of Staphylococcus aureus contains 2 major secondary cell wall glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Both CP and WTA are attached to the cell wall and play distinct roles in S. aureus colonization, pathogenesis, and bacterial evasion of host immune defenses.

Integrating research on bacterial pathogens and commensals to fight infections-an ecological perspective.

The incidence of antibiotic-resistant bacterial infections is increasing, and development of new antibiotics has been deprioritised by the pharmaceutical industry. Interdisciplinary research approaches, based on the ecological principles of bacterial fitness, competition, and transmission, could open new avenues to combat antibiotic-resistant infections. Many facultative bacterial pathogens use human mucosal surfaces as their major reservoirs and induce infectious diseases to aid their lateral transmission to new host organisms under some pathological states of the microbiome and host.

Wall teichoic acid substitution with glucose governs phage susceptibility of .

The species- and clone-specific susceptibility of cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycosylation-dependent phage-WTA interactions in the opportunistic pathogen and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses.

Phage susceptibility determinants of the opportunistic pathogen Staphylococcus epidermidis.

Staphylococcus epidermidis is a common member of the human skin and nose microbiomes and a frequent cause of invasive infections. Transducing phages accomplish the horizontal transfer of resistance and virulence genes by mispackaging of mobile-genetic elements, contributing to severe, therapy-refractory S. epidermidis infections.

Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus.

Antagonistic bacterial interactions often rely on antimicrobial bacteriocins, which attack only a narrow range of target bacteria. However, antimicrobials with broader activity may be advantageous. Here we identify an antimicrobial called epifadin, which is produced by nasal Staphylococcus epidermidis IVK83.

Invasive uses a unique processive wall teichoic acid glycosyltransferase to evade immune recognition.

expresses glycerol phosphate wall teichoic acid (WTA), but some health care-associated methicillin-resistant (HA-MRSE) clones produce a second, ribitol phosphate (RboP) WTA, resembling that of the aggressive pathogen . RboP-WTA promotes HA-MRSE persistence and virulence in bloodstream infections. We report here that the TarM enzyme of HA-MRSE [TarM(Se)] glycosylates RboP-WTA with glucose, instead of -acetylglucosamine (GlcNAc) by TarM(Sa) in .

Wall Teichoic Acid Mediates Binding to Endothelial Cells via the Scavenger Receptor LOX-1.

The success of as a major cause for endovascular infections depends on effective interactions with blood-vessel walls. We have previously shown that uses its wall teichoic acid (WTA), a surface glycopolymer, to attach to endothelial cells. However, the endothelial WTA receptor remained unknown.

Secretory IgA impacts the microbiota density in the human nose.

Background: Respiratory mucosal host defense relies on the production of secretory IgA (sIgA) antibodies, but we currently lack a fundamental understanding of how sIgA is induced by contact with microbes and how such immune responses may vary between humans. Defense of the nasal mucosal barrier through sIgA is critical to protect from infection and to maintain homeostasis of the microbiome, which influences respiratory disorders and hosts opportunistic pathogens.

Methods: We applied IgA-seq analysis to nasal microbiota samples from male and female healthy volunteers, to identify which bacterial genera and species are targeted by sIgA on the level of the individual host.

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

Bacteria use quorum sensing (QS) to coordinate group behavior in response to cell density, and some bacterial viruses (phages) also respond to QS. In Staphylococcus aureus, the agr-encoded QS system relies on accumulation of auto-inducing cyclic peptides (AIPs). Other staphylococci also produce AIPs of which many inhibit S.

Keratinocytes use FPR2 to detect and initiate antimicrobial skin defense.

Introduction: Keratinocytes form a multilayer barrier that protects the skin from invaders or injuries. The barrier function of keratinocytes is in part mediated by the production of inflammatory modulators that promote immune responses and wound healing. Skin commensals and pathogens such as secrete high amounts of phenol-soluble modulin (PSM) peptides, agonists of formyl-peptide receptor 2 (FPR2).

The epidermal lipid barrier in microbiome-skin interaction.

The corneocyte layers forming the upper surface of mammalian skin are embedded in a lamellar-membrane matrix which repels harmful molecules while retaining solutes from subcutaneous tissues. Only certain bacterial and fungal taxa colonize skin surfaces. They have ways to use epidermal lipids as nutrients while resisting antimicrobial fatty acids.

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 among 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 initially produce small amounts of compound or show reduced growth rates.

Horizontal transfer and phylogenetic distribution of the immune evasion factor .

Methicillin-resistant (MRSA), a major human pathogen, uses the prophage-encoded gene as an important immune evasion factor. TarP glycosylates wall teichoic acid (WTA) polymers, major surface antigens, to impair WTA immunogenicity and impede host defence. However, phages appear to be restricted to only a few MRSA clonal lineages, including clonal complexes (CC) 5 and 398, for unknown reasons.

Sensitizing to antibacterial agents by decoding and blocking the lipid flippase MprF.

The pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. Multiple peptide resistance factor (MprF) is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistant (MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to antimicrobial agents 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.

Short-Chain Fatty Acid and FFAR2 Activation - A New Option for Treating Infections?

The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA production, especially acetate production, is usually essential for bacteria, and knockout of pathways involved in acetate production strongly impairs bacterial fitness.

Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases.

Neutrophil granulocytes act as a first line of defense against pathogenic staphylococci. However, has a remarkable capacity to survive neutrophil killing, which distinguishes it from the less-pathogenic Both species release phenol-soluble modulin (PSM) toxins, which activate the neutrophil formyl-peptide receptor 2 (FPR2) to promote neutrophil influx and phagocytosis, and which disrupt neutrophils or their phagosomal membranes at high concentrations. We show here that the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin G and proteinase 3, which are released into the extracellular space or the phagosome upon neutrophil FPR2 stimulation, effectively degrade PSMs thereby preventing their capacity to activate and destroy neutrophils.