The TIR Domain Containing Locus of<i>Enterococcus faecalis</i>Is Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response

Kraemer, Thomas; Haro, Orlando Daniel Quintanar; Domann, Eugen; Chakraborty, Trinad; Tchatalbachev, Svetlin

doi:10.1155/2014/918143

Cited by 17 publications

(19 citation statements)

References 26 publications

(52 reference statements)

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“…In addition, it was shown previously that gelatinase as well as the fsr quorum sensing system that regulates gelatinase expression does not contribute to NF-B immunomodulation (25,36). Finally, TcpF is present in E. faecalis V583 and enriched in UTI isolates, but it is absent in OG1RF (16,20). Since we observed NF-B modulation by both E. faecalis OG1RF and V583, TcpF is unlikely to be the factor mediating high-level NF-B suppression in macrophages.…”

Section: Fig 4 Legend (Continued)mentioning

confidence: 47%

“…TcpF is a TIR domaincontaining protein and interferes with Toll-like receptor (TLR)-MyD88 interactions, which also depend on MyD88 TIR domain-mediated interactions. As a result, E. faecalis TcpF expression results in decreased NF-B p65 translocation in RAW macrophages (16,20). Plasmid-encoded AS promotes phagocytosis and internalization into macrophages via interaction with complement receptor type 3 (21)(22)(23).…”

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confidence: 99%

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Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

et al. 2017

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, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. can subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examined-mediated subversion of macrophage activation. We observed that actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with and coinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that with infection alone. Finally, we demonstrated that coinoculation of with a commensal strain of into catheterized bladders significantly augmented CAUTI. Taken together, these results support the hypothesis that suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensal strains.

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Section: Fig 4 Legend (Continued)mentioning

confidence: 47%

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confidence: 99%

Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

et al. 2017

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“…In addition, there is a significant decrease in the number of infiltrating activated macrophages during E. faecalis CAUTI compared to catheterization in the absence of bacteria suggesting an immunosuppressive capacity of E. faecalis [31]. The gene encoding a Toll/interleukin-1 receptor (TIR) domain containing protein ( tcpF ) is enriched among E. faecalis UTI isolates and can downregulate the host inflammatory response, presumably by interfering via molecular mimicry with the TIR-TIR interactions between TLRs required for TLR dimerization and subsequent signaling [175, 176]. Consistent with this finding, several studies of E. faecalis strains isolated from the gastrointestinal tract of healthy human infant guts have shown that a subset of strains were capable of suppressing inflammatory cytokine expression in human intestinal epithelial cells in vitro , as well as suppressing cytokine responses in a Dextran Sulphate Sodium salt (DSS) model of inflammatory intestinal colitis in vivo , although the presence of tcpF was not examined in these strains [177–179].…”

Section: Urinary Tract Infection Caused By Enterococcimentioning

confidence: 99%

Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract

2016

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Gram-positive bacteria are a common cause of urinary tract infection (UTI), particularly among individuals who are elderly, pregnant, or who have other risk factors for UTI. Here we review the epidemiology, virulence mechanisms, and host response to the most frequently isolated Gram-positive uropathogens: Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae. We also review several emerging, rare, misclassified, and otherwise underreported Gram-positive pathogens of the urinary tract including Aerococcus, Corynebacterium, Actinobaculum, and Gardnerella. The literature strongly suggests that urologic diseases involving Gram-positive bacteria may be easily overlooked due to limited culture-based assays typically utilized for urine in hospital microbiology laboratories. Some UTIs are polymicrobial in nature, often involving one or more Gram-positive bacteria. We herein review the risk factors and recent evidence for mechanisms of bacterial synergy in experimental models of polymicrobial UTI. Recent experimental data has demonstrated that, despite being cleared quickly from the bladder, some Gram-positive bacteria can impact pathogenic outcomes of co-infecting organisms. When taken together, the available evidence argues that Gram-positive bacteria are important uropathogens in their own right, but that some can be easily overlooked because they are missed by routine diagnostic methods. Finally, a growing body of evidence demonstrates that a surprising variety of fastidious Gram-positive bacteria may either reside in or be regularly exposed to the urinary tract and further suggests that their presence is widespread among women, as well as men. Experimental studies in this area are needed; however, there is a growing appreciation that the composition of bacteria found in the bladder could be a potentially important determinant in urologic disease, including susceptibility to UTI.

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“…As a result, E. faecalis TcpF expression results in decreased NF-κB p65 translocation in RAW macrophages [30, 36]. TcpF is present in E. faecalis V583 and is enriched in UTI isolates, but is absent in OG1RF [30, 36]. Since we observed NF-κB modulation by both E. faecalis OG1RF and V583, TcpF is unlikely to be the factor mediating high-level NF-κB suppression in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…TcpF is a TIR domain-containing protein and interferes with Toll-like receptor (TLR)-MyD88 interactions, which also depend on MyD88 TIR domain-mediated interactions. As a result, E. faecalis TcpF expression results in decreased NF-κB p65 translocation in RAW macrophages [30, 36]. TcpF is present in E. faecalis V583 and is enriched in UTI isolates, but is absent in OG1RF [30, 36].…”

Section: Discussionmentioning

confidence: 99%

Enterococcus faecalispromotes innate immune suppression and polymicrobial catheter-associated urinary tract infection

Tien

Goh

Chong

et al. 2017

Preprint

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Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. E. faecalis and E. coli co-infection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to E. coli infection alone. Finally, we demonstrated that co-inoculation of E. faecalis with E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis.Author SummarySynergistic polymicrobial infections can contribute to both disease severity and persistence. Enterococcus faecalis and Escherichia coli are frequently co-isolated from polymicrobial urinary tract infections. Immunomodulation by co-infecting microbes can result in a more permissive environment for pathogens to establish infection. Presently, we do not yet understand how these microbes overcome host immunity to establish polymicrobial infections. To address this, we investigated how the immunosuppressive function of E. faecalis can contribute to acute infection. We defined that E. faecalis is able to suppress macrophages in vitro, despite the presence of E. coli. We also demonstrated E. faecalis’ ability to augment E. coli titers in vivo to establish kidney infection. Our findings raise the prospect that E. faecalis can alter host immunity to increase susceptibility to other uropathogens.

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The TIR Domain Containing Locus ofEnterococcus faecalisIs Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response

Cited by 17 publications

References 26 publications

Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract

Enterococcus faecalispromotes innate immune suppression and polymicrobial catheter-associated urinary tract infection

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