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

Yang, Jingxian; Bowring, Janine Zara; Krusche, Janes; Lehmann, Esther; Bejder, Benjamin Svejdal; Silva, Stephanie Fulaz; Bojer, Martin Saxtorph; Grunert, Tom; Peschel, Andreas; Ingmer, Hanne

doi:10.1016/j.celrep.2023.113154

Cited by 10 publications

(4 citation statements)

References 57 publications

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“…Accordingly, S. aureus phage RBPs are probably not subjected to major selection pressure, which might explain the high similarity of RBPs of the individual clusters. Nonetheless, our data clearly indicate that TarM does not only protect S. aureus from podovirus infection (Li et al, 2015; Yang et al, 2023), but can also prevent infection by various myoviruses (Figure 3b). This role underlines the importance of TarM in the evolutionary defense against phages.…”

Section: Discussionmentioning

confidence: 71%

“…This strategy enables the investigation of the host range of newly isolated S. aureus phages, as well as some of the S. epidermidis myoviruses. Using this approach, we were able to find phages with similar host range as myovirus ΦStab20 and we could show that agr- mediated downregulation of tarM can impact infection of S. aureus by multiple different myoviruses (Yang et al, 2023). These myoviruses show only low overall genome similarity to ΦStab20 but were found to carry RBPs with high similarity to the ΦStab20 RBPs, and their infection behavior matched that of ΦStab20.…”

Section: Discussionmentioning

confidence: 99%

“…It is present in the majority of S. aureus strains, while the accessory glycosyltransferases TarM (responsible for WTA α-1,4-GlcNAc modification) and TarP (WTA β-1,3-GlcNAc modification) can only be found in 37% and 7% of S. aureus strains, respectively (Brown et al, 2012; Gerlach et al, 2018; Gerlach et al, 2022; Tamminga et al, 2022; Xia et al, 2010). Changes in WTA glycosylation have been shown to impact phage binding and resistance to some phages (Li et al, 2015; Winstel et al, 2014; Yang et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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

Krusche,

Beck,

Lehmann

et al. 2024

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SummaryWall 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 inStaphylococcus 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 Φ13-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.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Krusche,

Beck,

Lehmann

et al. 2024

Preprint

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“…Phage-mediated changes in quorum sensing gene regulation within a bacterial population can create an environment that is more permissible for infection (24, 25). For example, changes in quorum sensing can result in the modification of wall teichoic acids, a major phage receptor, which contributes to phage infectivity (28, 29). In E. faecalis , high levels of the quorum-sensing peptide AI-2 are associated with release of prophages, possibly resulting in the transfer of virulence genes (26).…”

Section: Introductionmentioning

confidence: 99%

Enterococcal quorum-controlled protease alters phage infection

Sheriff,

Salvato,

Andersen

et al. 2024

Preprint

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Increased prevalence of multidrug resistant bacterial infections has sparked interest in alternative antimicrobials, including bacteriophages (phages). Limited understanding of the phage infection process hampers our ability to utilize phages to their full therapeutic potential. To understand phage infection dynamics we performed proteomics on Enterococcus faecalis infected with the phage VPE25. We discovered numerous uncharacterized phage proteins are produced during phage infection of Enterococcus faecalis. Additionally, we identified hundreds of changes in bacterial protein abundances during infection. One such protein, enterococcal gelatinase (GelE), an fsr quorum sensing regulated protease involved in biofilm formation and virulence, was reduced during VPE25 infection. Plaque assays showed that mutation of either the fsrA or gelE resulted in plaques with a halo morphology and significantly larger diameters, suggesting decreased protection from phage infection. GelE-associated protection during phage infection is dependent on the murein hydrolase regulator LrgA and antiholin-like protein LrgB, whose expression have been shown to be regulated by GelE. Our work may be leveraged in the development of phage therapies that can modulate the production of GelE thereby altering biofilm formation and decreasing E. faecalis virulence.

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