Multidrug-resistance efflux pumps ? not just for resistance

Abstract

It is well established that multidrug-resistance efflux pumps encoded by bacteria can confer clinically relevant resistance to antibiotics. It is now understood that these efflux pumps also have a physiological role(s). They can confer resistance to natural substances produced by the host, including bile, hormones and host-defence molecules. In addition, some efflux pumps of the resistance nodulation division (RND) family have been shown to have a role in the colonization and the persistence of bacteria in the host. Here, I present the accumulating evidence that multidrug-resistance efflux pumps have roles in bacterial pathogenicity and propose that these pumps therefore have greater clinical relevance than is usually attributed to them.

The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria

“…This regulon, which was described in Enterobacteriaceae, comprises a repressor (marR) that binds to an operator (marO) upstream of an activator [5][6][7] (marA). De-repression of marA in response to several chemical and antibiotic stresses triggers a cascade of events that results in global control of membrane permeability by the downregulation of porin synthesis and overexpression of efflux pump components [5][6][7][8]15,42 . In K. pneumoniae, several isolates have an insertion sequence (such as Is5 and Is26) in the OmpK36 and OmpK35 genes [43][44][45] .…”

“…There are two different aspects to transport systems across the bacterial membrane -influx and efflux. Here, we focus on the influx of antibiotics, as the efflux has been extensively discussed in recent reviews [5][6][7][8] .…”

Creatinine inhibits bacterial replication

“…We hypothesized therefore that only the protonated form 13 of CRN inhibited the growth of diverse bacterial species, perhaps by overwhelming the bacterial cells capacity to pump out protons. 14,15 To test this hypothesis, we used CCCP 14 (carbonyl cyanide 3-chlorophenylhydrazone; Sigma-Aldrich) to disrupt the proton gradient in cultures of E. coli, S. aureus, and B. subtilis. Tube cultures from diluted overnight cultures were established as described above, each containing the concentration of CCCP and CRN-HCl noted in the figure.…”

The contribution of PmrAB to the virulence of a clinical isolate ofEscherichia coli

“…[1][2][3][4] The three related transcription factors, MarA, Rob, and SoxS, act in both individual and redundant manners to affect antibiotic resistance and virulence of Escherichia coli, through known and unknown mechanisms. 5,6 These three transcription factors play a key role in the persistence of E. coli in a murine kidney infection model, where deletion of all three genes significantly decreases the bacterial load in the kidney after three days of successful colonization.…”