Mig‐14 is an inner membrane‐associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection

Abstract

SummarySalmonella enterica serovar Typhimurium ( S. typhimurium ) infects a wide variety of mammalian hosts and in rodents causes a typhoid-like systemic disease involving replication of bacteria inside macrophages within reticuloendothelial tissues. Previous studies demonstrated that the mig-14 and virK genes of Salmonella enterica are important in bacterial resistance to anti-microbial peptides and are necessary for continued replication of S. typhimurium in the liver and spleen of susceptible mice after orogastric inoculation. In this work we report that inflammatory signalling via interferon-gamma (IFN-g g g g ) is crucial to controlling replication of mig-14 mutant bacteria within the liver and spleen of mice after oral infection. Using a Salmonella persistence model recently developed in our laboratory, we further demonstrate that mig-14 contributes to long-term persistence of Salmonella in the spleen and mesenteric lymph nodes of chronically infected mice. Both mig-14 and virK contribute to the survival of Salmonella in macrophages treated with IFN-g g g g and are necessary for resistance to cathelin-related anti-microbial peptide (CRAMP), an anti-microbial peptide expressed at high levels in activated mouse macrophages. We also show that both Mig-14 and VirK inhibit the binding of CRAMP to Salmonella , and demonstrate that Mig-14 is an inner membrane-associated protein. We further demonstrate by transmission electron microscopy that the primary locus of CRAMP activity appears to be intracytoplasmic, rather than at the outer membrane, suggesting that Mig-14 may prevent the penetration of the inner membrane by CRAMP. Together, these data indicate an important role for mig-14 in antimicrobial peptide resistance in vivo , and show that this resistance is important to the survival of Salmonella in systemic sites during both acute and persistent infection.

Transcription factor function and promoter architecture govern the evolution of bacterial regulons

“…Given the degree of sequence identity between the sensing domains of the Salmonella and Yersinia PhoQ proteins (35), the virulence attenuation of the Salmonella strain expressing the Yersinia phoPQ operon is unlikely to result from a defect in the sensing ability of the Yersinia PhoQ protein. Rather, it may ref lect that Salmonella virulence demands the expression of horizontally acquired PhoP-dependent genes, such as mig-14 (36) and mgtC (24), whose promoters share the location and orientation of the PhoP box with the ugtL promoter (Fig. 3A) and thus are not efficiently transcribed by the Y. pestis PhoP protein (data not shown).…”

Inactivation of Nitrosomonas europaea and pathogenic Escherichia coli by chlorine and monochloramine

“…It is possible that these layers are responsible for the greater resistance to oxidants observed with N. europaea in comparison with E. coli O157:H7. In other studies, intracytoplasmic membranes have been associated with bacterial resistance to antimicrobial peptides (Brodsky et al 2005), toxic heavy metals (Itoh et al 1998),…”

Salmonella transcriptional signature in Tetrahymena phagosomes and role of acid tolerance in passage through the protist

“…The PhoP-PhoQ system is required for survival of S. Typhimurium and expression of SPI-2 genes within macrophages (Miller et al, 1989;Fass and Groisman, 2009). PagP is involved in remodeling of the lipid-A domain of lipopolysaccharide (Bishop, 2005), whereas Mig-14 and VirK promote resistance to antimicrobial peptides produced in macrophages (Brodsky et al, 2005). Low amounts of Ca 2 þ and Mg 2 þ (Groisman, 2001), acidic pH (Prost et al, 2007) and antimicrobial peptides (Bader et al, 2005) are the environmental cues for PhoPQ-mediated regulation.…”