Staphylococcus aureus response and adaptation to vancomycin

Advances in microbial physiology/Advances in Microbial Physiology, Год журнала: 2024, Номер unknown, С. 201 - 258

Опубликована: Янв. 1, 2024

Язык: Английский

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Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis

Cell Reports, Год журнала: 2025, Номер 44(3), С. 115369 - 115369

Опубликована: Фев. 28, 2025

Highlights•Receptor-binding proteins (RBPs) of 335 S aureus phages were identified•Most S. encode two distinct RBPs•15 recombinant RBPs bound to wall teichoic acid (WTA) polymers•The new PhARIS tool predicts the host binding phagesSummaryBacteriophages are crucial in bacterial communities and can be used for therapy multidrug-resistant pathogens such as Staphylococcusaureus. However, range remains difficult predict. We identified receptor-binding aureus-infecting phages, yielding 8 RBP clusters. Recombinant representative all clusters, including several subclusters, analyzed strains differing potential phage receptor structures. Notably, most encoded separate RBPs, polymers receptors, albeit with varying preference WTA glycosylation patterns backbone Based on these findings, a sequence-based predicting adsorption was developed. Moreover, one proved useful identifying aureus-type other species. These findings facilitate characterization isolates development therapies.Graphical abstract

Язык: Английский

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In Vitro Adhesion and Invasion Rates of Staphylococcus aureus Isolated from Mastitic Cows Are Modulated by the agr System and MSCRAMM Genes

Veterinary Sciences, Год журнала: 2025, Номер 12(3), С. 270 - 270

Опубликована: Март 13, 2025

Mastitis, an inflammatory condition of the udder, can be caused by entry Staphylococcus aureus, whose adhesion to mammary epithelial cells is influenced virulence factors such as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and accessory gene regulator (agr) system. Our goal was determine invasion rates S. aureus isolates from clinical (mild moderate) subclinical mastitis assess impact MSCRAMM genes agr types on disease severity. Clinical predominantly carried agrII (p < 0.0083) multiple genes, correlating with high capacity but reduced regardless Remarkably, isolates, mainly agr-negative (85.7%), showed increased cellular 0.0001), possibly due expression agr-mediated factors. These findings contribute understanding pathogen–host dynamics in bovine highlight importance both MSCRAMMs system modulating insights inform targeted interventions for prevention treatment.

Язык: Английский

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Decoding the evolutionary history of ST30 Staphylococcus aureus: insights into a potentially silent MSSA bloodstream pathogen

Frontiers in Microbiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 9, 2025

Staphylococcus aureus clonal complex 30 (CC30) is a historically significant pathogen affecting both hospital and community settings. The notable pandemic clones, phage-type 80/81 (PT80/81) the Southwest Pacific clone (SWP) have spread internationally, contributing to morbidity mortality. Despite their importance, research on evolution of sequence type (ST) has been limited, often focusing small number strains or specific regions. In this study, we analyzed over 500 ST30 genomes from diverse sources, including Brazilian sequenced by our team, using genomic, pangenomic, phylogenetic, time-calibrated phylogenetic analyses. We traced key evolutionary events, estimating that specialization PT80/81 SWP occurred after divergence around 1868, forming group PT80/81-related another formed SWP-related strains. Our findings highlight major events involving gene acquisition loss, as well mobile genetic elements (MGE). Notably, lost most lpl genes during diversification, which may restricted circulation related Contemporary strains-defined those emerged in 21st century-predominantly cluster within divided into three subgroups, acquired novel pathogenicity island. Also clustering contemporary group, toxic shock syndrome toxin-1 (TSST-1)-producing are methicillin-susceptible S. (MSSA) gained additional virulence traits, sea, enhance adaptability virulence. study revises history uncovering critical pathoadaptive explain its success. Additionally, emphasize neglected issue: high prevalence MSSA infections, particularly silent TSST-1 producing strains, capable causing severe infections. Robust surveillance studies monitor these crucial.

Язык: Английский

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The Capsular Polysaccharide Obstructs Wall Teichoic Acid Functions in Staphylococcus aureus

The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(5), С. 1253 - 1261

Опубликована: Май 14, 2024

Abstract Background The cell envelope of Staphylococcus aureus contains 2 major secondary wall glycopolymers: capsular polysaccharide (CP) and teichoic acid (WTA). Both CP WTA are attached to the play distinct roles in S. colonization, pathogenesis, bacterial evasion host immune defenses. We aimed investigate whether interferes with WTA-mediated properties. Methods Strains natural heterogeneous expression CP, strains homogeneous high expression, CP-deficient were compared regarding WTA-dependent phage binding, adhesion, IgG deposition, virulence vivo. Results adsorption, specific antibody adhesion negatively correlated expression. WTA, but not enhanced burden a mouse abscess model, while overexpression resulted intermediate Conclusions protects bacteria from opsonization binding. This protection comes at cost diminished cells. highly complex regulation mostly has probably evolved ensure survival optimal physiological adaptation population as whole.

Язык: Английский

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Recognition of Staphylococcus aureus by the pattern recognition molecules langerin, mannan-binding lectin, and surfactant protein D: the influence of capsular polysaccharides and wall teichoic acid

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

The innate immune system plays a critical role in the rapid recognition and elimination of pathogens through pattern receptors (PRRs). Among these PRRs are C-type lectins (CTLs) langerin, mannan-binding lectin (MBL), surfactant protein D (SP-D), which recognize carbohydrate patterns on pathogens. Each represents proteins from different compartments body employs separate effector mechanisms. We have investigated their interaction with Gram-positive opportunistic pathogen Staphylococcus aureus, bacterium whose cell wall contains two key glycopolymers: capsular polysaccharide (CP) teichoic acid (WTA). Using langerin-expressing line recombinant MBL, SP-D, we demonstrated that SP-D all nonencapsulated S. aureus. However, may produce CP effectively shields aureus by three CTLs. Experiments utilizing mutant strains confirmed WTA is ligand for but langerin likely interacts an additional unknown ligand. A competition assay revealed MBL inhibit langerin's highlighting intricate redundancy cooperation within system. This study highlights dynamic interplay recognizing specific surface structures provides insight into how this evades recognition.

Язык: Английский

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Systematic classification of phage receptor-binding proteins predicts surface glycopolymer structure inStaphylococcuspathogens

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 4, 2024

Summary Wall teichoic acids (WTAs) are major surface polymers of staphylococcal pathogens and commensals, whose variable structure governs interaction with host receptors, immunoglobulins, bacteriophages. The ribitol phosphate (RboP) WTA type contributes to virulence, for instance in Staphylococcus aureus , but we lack comprehensive knowledge types cognate phages. We developed a computational pipeline identify the receptor-binding proteins (RBPs) 335 phage genomes, yielding multiple distinct RBP clusters. Notably, many phages had two separate RBPs part different preferences. representatives differed specificity RboP glycosylation types, recapitulating corresponding phage. Based on these results, created publicly available bioinformatic tool predict based similarity. specific Φ13-RBP also revealed that presence non-aureus staphylococci is more common than previously thought. Our approach facilitates characterization opportunistic according which has implications phage-mediated interspecies horizontal gene transfer future therapies.

Язык: Английский

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Enterococcal quorum-controlled protease alters phage infection

FEMS Microbes, Год журнала: 2024, Номер 5

Опубликована: Янв. 1, 2024

Increased prevalence of multidrug-resistant bacterial infections has sparked interest in alternative antimicrobials, including bacteriophages (phages). Limited understanding the phage infection process hampers our ability to utilize phages their full therapeutic potential. To understand dynamics, we performed proteomics on

Язык: Английский

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The two-component system ArlRS is essential for wall teichoic acid glycoswitching inStaphylococcus aureus

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 10, 2024

Abstract Staphylococcus aureus is among the leading causes of hospital-acquired infections. Critical to S. biology and pathogenesis are cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third isolates decorates WTA with a mixture α1,4- β1,4- N -acetylglucosamine (GlcNAc), which requires dedicated glycosyltransferases TarM TarS, respectively. Environmental conditions, such as high salt concentrations, affect abundance ratio β1,4-GlcNAc decorations, thereby impacting biological properties antibody binding phage infection. To identify regulatory mechanisms underlying glycoswitching, we screened 1,920 mutants (Nebraska Transposon Mutant Library) by immunoblotting for differential expression WTA-linked or using specific monoclonal Fab fragments. Three two-component systems (TCS), GraRS, ArlRS, AgrCA, were 230 potential hits. Using isogenic TCS mutants, demonstrated that ArlRS essential decoration through regulation tarM but not tarS . regulated transcriptional regulator MgrA, was responsive Mg2+, Na+. Importantly, ArlRS-mediated glycosylation affected interaction innate receptor langerin lysis β1,4-GlcNAc-dependent phages. Since represents promising target future immune-based treatments vaccines, our findings provide important insight align targeting strategies patterns during Importance common colonizer mucosal surfaces, also frequent cause severe infections in humans. Development antibiotic resistance complicates treatment infections, increasing need alternatives vaccines therapies bacterial viruses known Wall (WTA) abundantly-expressed glycosylated structures have gained attention new treatments. show variation depending on environmental host factors, antibodies pattern-recognition receptors. Here, system its effector MgrA involved responding changes Mg 2+ concentration. These may support design

Язык: Английский

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The two-component system ArlRS is essential for wall teichoic acid glycoswitching in Staphylococcus aureus

mBio, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

ABSTRACT Staphylococcus aureus is among the leading causes of hospital-acquired infections. Critical to S. biology and pathogenesis are cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third isolates decorates WTA with a mixture α1,4- β1,4- N -acetylglucosamine (GlcNAc), which requires dedicated glycosyltransferases TarM TarS, respectively. Environmental conditions, such as high salt concentrations, affect abundance ratio β1,4-GlcNAc decorations, thereby impacting biological properties antibody binding phage infection. To identify regulatory mechanisms underlying glycoswitching, we screened 1,920 S . mutants (Nebraska Transposon Mutant Library) by immunoblotting for differential expression WTA-linked or using specific monoclonal Fab fragments. Three two-component systems (TCS), GraRS, ArlRS, AgrCA, were 230 potential hits. Using isogenic TCS mutants, demonstrated that ArlRS essential decoration. repressed tarM through transcriptional regulator MgrA. In bacteria lacking arlRS , increased correlated absence β1,4-GlcNAc, likely outcompeting TarS enzymatic activity. was responsive Mg 2+ but not Na + revealing its role in previously reported salt-induced glycoswitch from α1,4-GlcNAc β1,4-GlcNAc. Importantly, ArlRS-mediated regulation glycosylation affected interaction innate receptor langerin lysis β1,4-GlcNAc-dependent phages. Since represents promising target future immune-based treatments vaccines, our findings provide important insight align strategies targeting patterns during IMPORTANCE common colonizer can also cause severe infections humans. The development antibiotic resistance complicates treatment infections, increasing need alternatives vaccines therapies bacterial viruses known Wall (WTA) abundant glycosylated structures have gained attention new treatments. show variation depending on environmental host factors, antibodies pattern-recognition receptors. Here, system involved responding changes concentration. These may support design

Язык: Английский

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