Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Wang, Yanan; Hu, Mo; Liu, Qian; Qin, Juanxiu; Dai, Yingxin; He, Lei; Li, Tianming; Zheng, Bing; Zhou, Fan; Yu, Kaiwen; Fang, Jing‐Yuan; Liu, Xiaoyun; Otto, Michael; Li, Min

doi:10.1038/srep25163

Cited by 56 publications

(55 citation statements)

References 28 publications

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“…Similar phenotypes have been observed for essB variants of S. aureus ST398 isolates in mouse models for bloodstream infection and skin abscess formation (37). For ST398 isolates, expression of ess has been associated with neutrophil lysis and staphylococcal escape from phagocytic killing; however, it is not yet clear whether this phenotype is attributable to specific effectors secreted via the essC2 T7SS (37).…”

Section: Discussionmentioning

confidence: 58%

EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection

et al. 2017

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Staphylococcus aureus, an invasive pathogen of humans and animals, requires a specialized ESS pathway to secrete proteins (EsxA, EsxB, EsxC, and EsxD) during infection. Expression of ess genes is required for S. aureus establishment of persistent abscess lesions following bloodstream infection; however, the mechanisms whereby effectors of the ESS pathway implement their virulence strategies were heretofore not known. Here, we show that EssE forms a complex with other members of the ESS secretion pathway and its substrates, promoting the secretion of EsxA, EsxB, EsxC, EsxD, and EssD. During bloodstream infection of mice, the S. aureus essE mutant displays defects in host cytokine responses, specifically in the production of interleukin-12 (IL-12) (p40/p70) and the suppression of RANTES (CCL5), activators of T H 1 T cell responses and immune cell chemotaxis, respectively. Thus, essE-mediated secretion of protein effectors via the ESS pathway may enable S. aureus to manipulate host immune responses by modifying the production of cytokines.IMPORTANCE Staphylococcus aureus and other firmicutes evolved a specialized ESS (EsxA/ESAT-6-like secretion system) pathway for the secretion of small subsets of proteins lacking canonical signal peptides. The molecular mechanisms for ESSdependent secretion and their functional purpose are still unknown. We demonstrate here that S. aureus EssE functions as a membrane assembly platform for elements of the secretion machinery and their substrates. Furthermore, S. aureus EssEmediated secretion contributes to the production or the suppression of specific cytokines during host infection, thereby modifying immune responses toward this pathogen.

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Section: Discussionmentioning

confidence: 58%

EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection

et al. 2017

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“…Our data indicate that putative T7SS genes are activated in response to phage infection. Although E. faecalis T7SS remains poorly characterized, the Staphylococcus aureus T7 system has been demonstrated to defend cells against neutrophil assault, enhance epithelial cell apoptosis and is critical for virulence (68, 69, 78, 79). Additionally, S. aureus T7SS maintains membrane homeostasis and is involved in the membrane stress response (69, 80).…”

Section: Discussionmentioning

confidence: 99%

Parallel genomics uncover novel enterococcal-bacteriophage interactions

Chatterjee

Willett

Nguyen

et al. 2019

Preprint

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23 24 25 26 suggests that therapeutic phages could more broadly influence bacterial community composition 53 outside of their intended host targets. 54Recent studies have demonstrated the potential for phage-based therapies against systemic and 67 biofilm associated enterococcal infections (18)(19)(20)(21)(22). The decolonization of intestinal MDR E. 68 faecalis may be achieved through the action of phage predation which selects for cell wall variants 69 that are rendered sensitive to antibiotic therapy (23). However, a potential barrier to the wide-70 spread use of phage therapy against E. faecalis is the development of phage resistance. To 71 confront this issue, we must understand the molecular mechanisms used by phages to infect E. 72 faecalis and how E. faecalis overcomes phage infection to become resistant. Only then can this 73 biology be exploited to better develop phage therapies that mitigate the risk of developing phage 74 resistance. 75The study of phage-bacteria interactions has provided key insights into phage infection that 76 could lead to the development of novel antibacterial therapies. Phages replicate in bacteria by 77 sequence-defined mariner technology transposon sequencing (SMarT TnSeq) (33). 10 7 CFU of 104 logarithmically growing E. faecalis TnSeq library pool was plated on solid media in the absence 105 and presence of phage VPE25 at a multiplicity of infection (MOI) of 0.1. Cells from the input library 106 prior to plating and cells plated on plates containing no phage were used as controls. Tn insertions 107 in E. faecalis genomic DNA were sequenced as described by Dale et al. (33). Sequencing reads 108 were mapped to the E. faecalis OG1RF genome to identify bacterial mutants with altered phage 109 sensitivity. The relative abundance of 22 E. faecalis mutants was enriched (adjusted P value < 110 0.05, log2 fold change > 0) in the presence of VPE25 relative to cultures that lacked phage and 111 the input library (Table S1, Fig. 1A). Five of the 22 phage-resistant enriched mutants harbored Tn 112 insertions in OG1RF_10588 (Table S1, Fig. 1A), previously identified to encode the VPE25 113 receptor Phage Infection Protein of E. faecalis (PipEF) (32). This indicates that the Tn mutant 114

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“…The system, termed Ess (for 13 ESAT-6 secretion system), is required for virulence in murine abscess, 14 pneumonia and skin infection models [40][41][42] and is linked to the 15 establishment of persistent infection [40,43]. The ess genes showed high 16 levels of upregulation during chronic S. aureus infection in cystic fibrosis 17 patients [44], suggesting a similar role in persistent infection in humans.…”

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confidence: 98%

The Enigmatic Esx Proteins: Looking Beyond Mycobacteria

Unnikrishnan

Constantinidou

Palmer

et al. 2017

Trends in Microbiology

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1Bacteria export proteins across membranes using a range of transport 2 machineries. Type VII secretion systems (T7SSs), originally described in 3 mycobacteria, are now known to be widespread across diverse bacterial 4 phyla. Recent studies have characterized secretion components and 5 mechanisms of type VII secretion in pathogenic and environmental bacteria. A 6 variety of functions have been attributed to T7SS substrates, including 7interactions with eukaryotes and with other bacteria. Here, we evaluate the 8 growing body of knowledge on T7SSs, with focus on the non-mycobacterial 9 systems, reviewing their phylogenetic distribution, structure and function in 10 diverse settings. 11 12 3

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Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Cited by 56 publications

References 28 publications

EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection

EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection

Parallel genomics uncover novel enterococcal-bacteriophage interactions

The Enigmatic Esx Proteins: Looking Beyond Mycobacteria

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