Identification of the Salmonella enterica damX Gene Product, an Inner Membrane Protein Involved in Bile Resistance

Abstract

The damX gene product of Salmonella enterica serovar Typhimurium is a protein located in the inner membrane. DamX migrates as a 70-kDa protein in SDS-PAGE even though the predicted protein size is 46 kDa. Synthesis of DamX protein occurs in both exponential- and stationary-phase cultures. Disruption of damX causes severe sensitivity to bile. Lack of the outer membrane protein AsmA suppresses bile sensitivity in Salmonella damX mutants.

The DamX protein ofEscherichia coliandSalmonella enterica

“…In Salmonella enterica serovar Typhimurium, null damX alleles cause sensitivity to deoxycholate. 11 Similar results have been reported in E. coli. 10 Interestingly, a similar phenotype is observed in mutants lacking the downstream gene, dam.…”

“…10,11 (ii) Sensitivity to bile in S. enterica dam mutants is suppressed by inactivation of either the MutHLS system or the AsmA protein. 22,23 In S. enterica damX mutants, however, bile sensitivity is suppressed by inactivation of AsmA, but not by inactivation of the MutHLS system, suggesting that the causes of bile sensitivity in dam and damX mutants are different.…”

“…However, none of the bile-sensitive mutants so far identified has defects in septal ring components. DamX is an inner membrane protein, and its presence in both dividing and non-dividing cells 11 suggests that, besides its role in cytokinesis, DamX may contribute to the maintenance of envelope integrity (Fig. 2).…”

“…However, for reasons still unknown, the protein runs more slowly than expected in SDS polyacrylamide gels. 1,10,11 In both E. coli and Salmonella, DamX harbors a conserved peptidoglycanbinding domain at its C-terminus, known as the SPOR domain. 12 This domain is present in some septal ring components, and is thought to be important for septal ring localization (see below).…”

Metabolomics Reveals Phospholipids as Important Nutrient Sources during Salmonella Growth in Bile In Vitro and In Vivo

“…Salmonella not only can survive the antibacterial properties of bile but also can thrive in this harsh environment, producing growth rates comparable to those achieved in rich culture medium in the laboratory. Some of the mechanisms used by Salmonella to resist the antibacterial action of bile have been studied previously (3,14,(16)(17)(18)(19)(20)(21). However, most studies to date have focused on resistance to defined mixtures of bile salts/acids and have not yet addressed the interactions between Salmonella and "physiological" bile.…”