A New Role of OmpR in Acid and Osmotic Stress in Salmonella and E. coli

Abstract

Bacteria survive and respond to diverse environmental conditions and during infection inside the host by systematic regulation of stress response genes. E. coli and S. Typhimurium can undergo large changes in intracellular osmolality (up to 1.8 Osmol/kg) and can tolerate cytoplasmic acidification to at least pHi 5.6. Recent analyses of single cells challenged a long held view that bacteria respond to extracellular acid stress by rapid acidification followed by a rapid recovery. It is now appreciated that both S. Typhimurium and E. coli maintain an acidic cytoplasm through the actions of the outer membrane protein regulator OmpR via its regulation of distinct signaling pathways. However, a comprehensive comparison of OmpR regulons between S. Typhimurium and E. coli is lacking. In this study, we examined the expression profiles of wild-type and ompR null strains of the intracellular pathogen S. Typhimurium and a commensal E. coli in response to acid and osmotic stress. Herein, we classify distinct OmpR regulons and also identify shared OmpR regulatory pathways between S. Typhimurium and E. coli in response to acid and osmotic stress. Our study establishes OmpR as a key regulator of bacterial virulence, growth and metabolism, in addition to its role in regulating outer membrane proteins.

An acid-tolerance response system protecting exponentially growing Escherichia coli

“…Because AR2 system is responsible for survival below pH 3.0 and log phase cells with overexpression of AR2 genes are not more acid resistant 4 , the CpxRA-mediated repression of AR2 in exponentially growing cells above pH 3.0 will guarantee that AR2 system is not induced in an inappropriate situation to avoid the metabolic burden. Furthermore, the sensor kinase CpxA was proved to cross-talk with noncognate response regulator OmpR 64 , which itself is involved in the acid stress response of E. coli 65,66 . All of these data indicate that E. coli has Table 1 Putative CpxR box of fabA and fabB genes from Gram − bacteria (The genome sequences of various bacteria used in this table are under the accession numbers CP009273, NC_003197, NC_002516, NC_011283, NC_013716, CP001235, NC_004741, CP001589, evolved multiple acid response mechanisms as well as precise regulatory circuits, to target specific stress conditions.…”

Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment withEscherichia coli

“…4). OmpR is a transcriptional regulator involved in responses to osmotic and acid stress; mutations to OmpR also contribute to antibiotic resistance by altering the expression of the OmpF major porin (32)(33)(34). A recent study showed that ompF deletions reduce the permeability of β-lactams (e.g., ampicillin and ceftriaxone) across the outer membrane, thus increasing resistance (34).…”

EnvZ/OmpR Two-Component Signaling: An Archetype System That Can Function Noncanonically

“…The model was based on genetic analysis of a series of mutants that indicated that (i) OmpR~P was the form that regulated the porin genes and OmpR did not play a role (4) and (ii) EnvZ controls the concentration of OmpR~P via its biochemical activities (described in Section 1.7) (57). We now appreciate that OmpR plays a surprising, non-canonical role in regulating many genes (see section 3.6 and "New View") (2,3,24). The hypothesis is outlined briefly as follows: at low osmolality, there is a low level of OmpR~P present, either due to a low activity of the EnvZ kinase or a high activity of the EnvZ phosphatase.…”