We also observed that the sbmA upregulation in a tolC mutant context was abolished in an rpoE-null strain. These results suggest a σE-dependent positive regulation on sbmA by the tolC mutation. We hypothesize that this mechanism see more might be part of a compensatory cell envelope stress response. The SbmA protein was first identified in Escherichia coli as a consequence of the resistance phenotype of sbmA mutants to microcin B17 (sensitivity to B17 microcin, locus A) (Lavina et al., 1986).
Later, other studies showed that a mutation in sbmA confers resistance to bleomycin (Yorgey et al., 1994) and to the antibiotic peptide MccJ25 (Salomon & Farias, 1995). More recently, it was shown that Salmonella typhimurium mutants in the sbmA gene were about four times more resistant to several proline-rich peptides compared with the wild-type strain (Mattiuzzo et al., 2007). From the analysis of its 406 amino acids sequence, it was deduced that SbmA is an inner membrane protein with seven transmembrane domains (Glazebrook et al., 1993). Thus, Belnacasan it could be inferred that SbmA transports MccB17, MccJ25 and bleomycin into the cell cytoplasm, where their respective targets are located. SbmA appears to be dispensable for cell viability because no apparent growth phenotype was associated with sbmA mutants. This raises the question about the potential physiological role of this protein. It was found that
the Sinorhizobium meliloti bacA gene encodes a 420 amino acid protein that is 64% identical to SbmA, and is also predicted to span seven times the cytoplasmic membrane (Glazebrook et al., 1993). Furthermore, the SbmA protein is functionally interchangeable with S. meliloti BacA (Ichige & Walker, 1997). The BacA protein has been found to be required for the development of S. meliloti bacteroids within plant cells (Glazebrook et al., 1993). Similarly, in Brucella abortus BacA is vital for the survival of this mammalian pathogen
in macrophages, favoring chronic infections in BALB/c mice (LeVier et al., 2000). In both strains, bacA mutants have reduced lipid A very-long-chain fatty acid in their outer membrane Mirabegron (Ferguson et al., 2004). On the basis of the current knowledge about SbmA function (peptide transporter), it was postulated that the symbiotic role of BacA might involve the uptake of a signal from the eukaryotic cytoplasm to the bacterial cell, which would be important for intracellular development (Glazebrook et al., 1993; Ichige & Walker, 1997). Homologues of the BacA/SbmA proteins were found in a wide variety of free-living bacteria, including plant and animal pathogens (Glazebrook et al., 1993). Thus, functions related to that of BacA/SbmA must confer an important advantage in diverse environments. TolC forms a multifunctional outer membrane channel with roles in protein export and small noxious compounds efflux, mainly detergents and a wide range of antibacterial drugs (Nikaido, 1998; Thanassi & Hultgren, 2000).