Can enterococcal infections initiate sepsis syndrome?

Linden, Peter K.

doi:10.1007/s11908-003-0016-8

Cited by 14 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 Despite the general notion that these organisms possess low virulence, enterococci are frequently the causative organism identified with catheter-associated urinary tract infections (UTIs) and infective endocarditis. Although the independent capability of this organism to cause sepsis has been questioned earlier, [3][4][5][6] recent reports have shown that Enterococcus faecalis infection can lead to severe sepsis or septic shock in immunocompromised patients, burn patients and thermally injured mice, by modulation of the host systemic inflammatory response. [7][8][9] Lipoteichoic acid (LTA) has been reported earlier as an enterococcal PAMP recognized by host TLR2 to induce a signaling cascade that culminates in the activation of transcription factors and induction of pro-inflammatory cytokine expression.…”

Section: Introductionmentioning

confidence: 99%

Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection

Zou

Shankar

2015

Innate Immun

View full text Add to dashboard Cite

Enterococcal surface protein (Esp) is encoded on a pathogenicity island in Enterococcus faecalis and E. faecium and is involved in biofilm formation and binding to epithelial cells. In this study, using Esp-expressing E. faecalis MMH594 and its isogenic Esp-deficient strain, as well as purified Esp, we show that Esp is sufficient for activation of NF-kB and the subsequent production of pro-inflammatory cytokines IL-1b and TNF-a in macrophages in vitro. In a mouse peritonitis model, we also show that mice infected with Esp-expressing E. faecalis showed comparatively higher levels of cytokines TNF-a, IL-1b and IL-6 in peritoneal fluid, and IL-6 in serum. Moreover, neutrophil infiltration and tissue damage in the liver was higher in the mice infected with the Esp-expressing strain compared with mice infected with the Esp-deficient mutant. These results add Esp to the growing list of enterococcal virulence factors that can modulate inflammation during infection and has implications for enterococcal pathogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection

Zou

Shankar

2015

Innate Immun

View full text Add to dashboard Cite

show abstract

“…Despite being a commensal, Enterococcus faecalis is endowed with traits that make it an opportunistic pathogen, especially in immunocompromised hosts (1,2). Enterococci have emerged as a leading cause of antibiotic-resistant infections and now rank among the most common nosocomial pathogens infecting the bloodstream, surgical sites, and urinary tract (3,4).…”

mentioning

confidence: 99%

Enterococcus faecalis Infection Activates Phosphatidylinositol 3-Kinase Signaling To Block Apoptotic Cell Death in Macrophages

Zou

Shankar

2014

Infect Immun

View full text Add to dashboard Cite

Apoptosis is an intrinsic immune defense mechanism in the host response to microbial infection. Not surprisingly, many pathogens have evolved various strategies to manipulate this important pathway to benefit their own survival and dissemination in the host during infection. To our knowledge, no attempts have been made to explore the host cell survival signals modulated by the bacterium Enterococcus faecalis. Here, we show for the first time that during early stages of infection, internalized enterococci can prevent host cell (RAW264.7 cells, primary macrophages, and mouse embryonic fibroblasts [MEFs]) apoptosis induced by a wide spectrum of proapoptotic stimuli. Activation of caspase 3 and cleavage of the caspase 3 substrate poly(ADP-ribose) polymerase were inhibited in E. faecalis-infected cells, indicating that E. faecalis protects macrophages from apoptosis by inhibiting caspase 3 activation. This antiapoptotic activity in E. faecalis-infected cells was dependent on the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which resulted in the increased expression of the antiapoptotic factor Bcl-2 and decreased expression of the proapoptotic factor Bax. Further analysis revealed that active E. faecalis physiology was important for inhibition of host cell apoptosis, and this feature seemed to be a strain-independent trait among E. faecalis isolates. Employing a mouse peritonitis model, we also determined that cells collected from the peritoneal lavage fluid of E. faecalis-infected mice showed reduced levels of apoptosis compared to cells from uninfected mice. These results show early modulation of apoptosis during infection and have important implications for enterococcal pathogenesis.

show abstract

“…This bacterium is mainly responsible for bloodstream, urinary tract, and surgical site infections and endocarditis (32). Notably, E. faecalis seems to modulate the host systemic inflammatory response in mono-or polymicrobial infections, leading sometimes to severe sepsis or septic shock in immunocompromised patients (3,39). Several enterococcal virulence factors, such as lipoteichoic acid (6,64), aggregation substance, and enterococcal binding substance (56), have been implicated in the stimulation of the inflammatory response in vitro.…”

mentioning

confidence: 99%

Enterococcal Leucine-Rich Repeat-Containing Protein Involved in Virulence and Host Inflammatory Response

Brinster¹,

Posteraro

Bierne

et al. 2007

Infect Immun

View full text Add to dashboard Cite

Enterococcus faecalis is an important nosocomial pathogen associated with high morbidity and mortality for patients who are immunocompromised or who have severe underlying diseases. The E. faecalis genome encodes numerous surface-exposed proteins that may be involved in virulence. This work describes the characterization of the first internalin-like protein in E. faecalis, ElrA, belonging to the recently identified WxL family of surface proteins. ElrA contains an N-terminal signal peptide for export, a leucine-rich repeat domain that may interact with host cells, and a C-terminal WxL domain that interacts with the peptidoglycan. Disruption of the elrA gene significantly attenuates bacterial virulence in a mouse peritonitis model. The elrA deletion mutant also displays a defect in infection of host macrophages and a decreased interleukin-6 response in vivo. Finally, elrA expression is induced in vivo. Altogether, these results demonstrate a role for ElrA in the E. faecalis infectious process in vivo and suggest that this surface protein may contribute to E. faecalis virulence by stimulating the host inflammatory response.Enterococci belong to the normal gastrointestinal tract microflora of hosts ranging from mammals to insects. Even if considered opportunistic pathogens, enterococci are a major cause of nosocomial infections in North America and in Europe (7, 33, 52), with Enterococcus faecalis being the most common enterococcal species. This bacterium is mainly responsible for bloodstream, urinary tract, and surgical site infections and endocarditis (32). Notably, E. faecalis seems to modulate the host systemic inflammatory response in mono-or polymicrobial infections, leading sometimes to severe sepsis or septic shock in immunocompromised patients (3, 39). Several enterococcal virulence factors, such as lipoteichoic acid (6, 64), aggregation substance, and enterococcal binding substance (56), have been implicated in the stimulation of the inflammatory response in vitro. Like the capsular polysaccharides Epa and Cps (29,31,62) and transcriptional regulators HypR and Ers (24,67,68), the aggregation substance is involved in the resistance to macrophages and/or to phagocytosis (50,61,65).Bacteria have evolved a plethora of sophisticated molecular mechanisms to adhere to and invade host cells and tissues and to resist host defenses (49). Interestingly, several proteins with well-known roles in host-pathogen interactions, such as SspH of Salmonella enterica serovar Typhimurium The best-characterized bacterial LRR proteins, InlA and InlB of Listeria monocytogenes, are the prototypes of an internalin multigene family of Listeria spp. Both proteins impact on L. monocytogenes virulence by interacting with host cell receptors in a species-specific manner and inducing endocytic pathways for invasion of and dissemination in tissues (28). Internalin-like proteins have been recently predicted in genomes of several gram-positive bacteria (8,48,54,69). All characterized or predicted internalins are assigned to cell surface or ...

show abstract

Can enterococcal infections initiate sepsis syndrome?

Cited by 14 publications

References 56 publications

Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection

Surface protein Esp enhances pro-inflammatory cytokine expression through NF-κB activation during enterococcal infection

Enterococcus faecalis Infection Activates Phosphatidylinositol 3-Kinase Signaling To Block Apoptotic Cell Death in Macrophages

Enterococcal Leucine-Rich Repeat-Containing Protein Involved in Virulence and Host Inflammatory Response

Contact Info

Product

Resources

About