Biology subjects

Krusche, J.

Publications and source records attributed to Krusche, J..

3 recordsLinked to original sources

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↗

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

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↗