Mechanisms of antibiotic resistance in enterococci

Abstract

Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.

Keywords: antimicrobial resistance; enterococcus; mechanisms of resistance; vancomycin-resistant enterococci.

Figure 1. Proposed mechanisms of daptomycin resistance in enterococci

Two main mechanisms have been postulated to mediate DAP resistance in enterococci. The first is diversion of the antibiotic from the septum (black arrow) by redistribution of cardiolipin microdomains away from the division plane at the septum level. This mechanism, characterized in Enterococcus faecalis only, is initially mediated by substitutions in the LiaFSR signaling system that controls cell envelope homeostasis. Changes in phospholipid synthesis enzymes (cardiolipin synthase and possibly a glycerol-phosphodiester phosphodiesterase) complete the resistance phenotype. The second mechanism, seen in E. faecium, is electrostatic repulsion of the positively charged daptomycin/calcium complex from the cell membrane. Several genes may be involved in this mechanism. DAP: Daptomycin.