Enterococcus faecalis aggregation substance promotes opsonin-independent binding to human neutrophils via a complement receptor type 3-mediated mechanism

Abstract

Enterococcus faecalis aggregation substance (AS) mediates efficient adhesion between bacteria, thereby facilitating plasmid exchange as an integral part of a bacterial sex pheromone system. We examined the interaction of AS-bearing E. faecalis with human neutrophils (PMNs), an important component of the host defense system. AS promoted a markedly increased opsonin-independent bacterial binding to PMNs. Adhesion was dependent on the expression of the enterococcal Asc10 protein, which contains two Arg-Gly-Asp (RGD) sequences, and addition of exogenous RGD-containing peptides inhibited AS-mediated binding by 66%. AS-mediated adhesion was inhibited by 85% by anti-human complement receptor type 3 (CR3) monoclonal antibodies or by use of PMNs from a patient with leukocyte adhesion deficiency. However, AS-bearing E. faecalis cells were unable to bind to CHO-Mac-1 cells, expressing functionally active CR3, suggesting the potential need for additional PMN surface receptors for bacterial adhesion. Monoclonal antibodies against integrin-associated protein (CD47) and L-selectin, both of which may interact with CR3 and bind to ligands on E. faecalis, also inhibited AS-dependent binding. The non-opsonic binding of E. faecalis to PMNs may play an important role in this organism's pathogenesis.

In Vivo Induction of Virulence and Antibiotic Resistance Transfer in Enterococcus faecalis Mediated by the Sex Pheromone-Sensing System of pCF10

“…Increased adhesion to renal tubular cells was demonstrated (28). AS promoted increased association of E. faecalis with polymorphonuclear leukocytes (PMNs) (35,42) and macrophages (39), whereby uptake of the bacteria failed to trigger the normal killing mechanisms of these cells, such as lowered phagosomal pH and the oxidative burst, presumably enabling cells expressing AS to evade host defenses. Fewer data are available for animal models that examined the ability of AS to act as a virulence factor in vivo.…”

Biological Diversity of Prokaryotic Type IV Secretion Systems

“…PrgB is a large ϳ137-kDa protein with homologs identified primarily in related pheromone-inducible conjugative plasmids in en- terococci. In addition to an N-terminal signal sequence and C-terminal LPXTG cell wall anchor motif, PrgB contains internal RGD motifs and aggregation domains shown to be important for the binding of lipoteichoic acid, adherence to eukaryotic cells, and bacterial internalization by epithelial cells (see below) (65,67,221,266,284,285,286). prgB mutants show reductions in pCF10 transfer efficiencies by several orders of magnitude, although transfer still occurs on solid surfaces.…”

Características microbiológicas, patogenicidade e viabilidade do Entercoccus faecalis e seu cultivo in vitro em pesquisas microbiológicas na área da Endodontia

“…Entre os fatores de virulência, estão a produção de substância de agregação, ácido lipopoliteicoico, adesinas de superfície, produção extracelular de superóxido, enzima lítica gelatinase e hialuronidase 15 . A substância de agregação (SA) é uma adesina bacteriana de natureza proteica e codificada por plasmídeo, que permite o contato entre o hospedeiro e o receptor da bactéria por meio de uma substância ligante (SL), garantindo a troca de plasmídeos e uma eficiente adesão e ação do E. faecalis, tornando-os resistentes à fagocitose por neutrófilos humanos [15][16][17] . A associação de SA com a SL apresenta atividade de superantígeno 18 , caracterizada pela prolife ração de linfócitos T e estimulação da liberação de TNF alfa pelos macrófagos, que irão atuar na reabsorção óssea, e de Interferon gama, que ativará a produção de agente citotóxico ácido nítrico, causando a destruição celular 15 .…”