Antimicrobial Peptides Activate the Rcs Regulon through the Outer Membrane Lipoprotein RcsF

Abstract

Salmonella enterica species are exposed to envelope stresses due to their environmental and infectious lifestyles. Such stresses include amphipathic cationic antimicrobial peptides (CAMPs), and resistance to these peptides is an important property for microbial virulence for animals. Bacterial mechanisms used to sense and respond to CAMP-induced envelope stress include the RcsFCDB phosphorelay, which contributes to survival from polymyxin B exposure. The Rcs phosphorelay includes two inner membrane (IM) proteins, RcsC and RcsD; the response regulator RcsB; the accessory coregulator RcsA; and an outer membrane bound lipoprotein, RcsF. Transcriptional activation of the Rcs regulon occurred within minutes of exposure to CAMP and during the first detectable signs of CAMP-induced membrane disorder. Rcs transcriptional activation by CAMPs required RcsF and preservation of its two internal disulfide linkages. The rerouting of RcsF to the inner membrane or its synthesis as an unanchored periplasmic protein resulted in constitutive activation of the Rcs regulon and RcsCD-dependent phosphorylation. These findings suggest that RcsFCDB activation in response to CAMP-induced membrane disorder is a result of a change in structure or availability of RcsF to the IM signaling constituents of the Rcs phosphorelay.

Exploring the relationship between lipoprotein mislocalization and activation of the Rcs signal transduction system in Escherichia coli

“…In response to environmental or mutational stimuli RcsF may change its conformation, leading to direct interaction with the RcsC periplasmic domain and to activation of Rcs signalling. A similar mechanism for Rcs activation has been proposed by Farris et al (2010). RcsD shows high similarity to RcsC, except for the C-terminal phosphotransmitter domain (Takeda et al, 2001).…”

“…6c). Farris et al (2010) have also reported periplasmic mislocalization of mature RcsF fused to the PagC signal sequence and consequent Rcs activation in S. enterica. The faint spots at the positions between CL and PG in lanes 2 and 3 are phosphatidic acid, which accumulates in small amounts in pgsA null cells (Kikuchi et al, 2000).…”

“…5c). We note that innermembrane retention of RcsFS2D causing Rcs activation has recently been reported in Salmonella enterica (Farris et al, 2010).…”

Salmonella spp. survival strategies within the host gastrointestinal tract

“…Further research is necessary to investigate other molecular mechanisms employed by Salmonella to tolerate host-produced antimicrobial peptides in the intestine. It is possible that the systems that have been shown to be important for the tolerance of antimicrobials in the macrophage phagosome, such as PhoPQ, PmrAB and RcsCDB (Bader et al, 2003;Farris et al, 2010), might be involved. Salmonella may also have to tolerate antimicrobial peptides produced by gut bacteria, i.e.…”

Regulation of bacterial virulence gene expression by cell envelope stress responses

“…110 Nevertheless, polysaccharide capsules are widely conserved and in some cases they are virulence factors associated with resistance to phagocytosis and to host antimicrobial molecules. [111][112][113] Furthermore, the Rcs response has been implicated in regulating production of E. coli group I capsules, which are important virulence determinants. In some E. coli strains the production of group I capsule was induced by overexpression of rcsB.…”