Fe³⁺-dependent epistasis between the CpxR-activated loci and the PmrA-activated LPS modification loci in <i>Salmonella enterica</i>

Abstract

Bacteria utilize varying combinations of twocomponent regulatory systems, many of which respond and adapt closely to stress conditions, thus expanding their niche steadily. While mechanisms of recognition and avoidance of the specific Fe 3+ signal by the PmrA/PmrB system is well understood, those of the CpxR/CpxA system are more complex because they can be induced by various stress conditions, which, in turn, expresses a variety of phenotypes. Here, we highlight another aspect of the CpxR/CpxA system; mutations in degP and yqjA genes, which are under the control of the system, exhibit an iron sensitive phenotype in the mutant background defective in the PmrA-dependent gene products that alter the pyrophosphate status of the lipid A moiety of lipopolysaccharide in Salmonella enterica. Therefore, after the PmrA/ PmrB-mediated Fe 3+ -dependent control of the pyrophosphate status on the cell surface, the CpxR/ CpxA system is one of the second layers of envelope stress response that allows adaptation to high Fe 3+ conditions in this bacterium.

New Roles for Two-Component System Response Regulators of Salmonella enterica Serovar Typhi during Host Cell Interactions

“…CpxA (STY3813) CpxR (STY3812) Membrane stress (AMR and metal resistance) [48][49][50][51][52]; SPI-1 repression [53,54] and SPI-2 regulation [55]; virulence [53,55,56] CreC (STY4936) CreB (STY4935) Carbon source metabolism a [57] DcuS (STY4502) DcuR (STY4501) C4-dicarboxylates catabolism a [57][58][59] DpiB (STY0674) DpiA (STY0675) SOS response a [60] GlnL (STY3875) GlnG (STY3876) Nitrogen response [61,62] HydH (STY3712) HydG (STY3211) Zinc transport a [63] KdpD (STY0744) KdpE (STY0743) Potassium transport [64], C. elegans colonization [65] NarX (STY1286) NarL (STY1285) Nitrate responsive [66,67] NarQ (STY2718) NarP (STY2472) Nitrate respiration [66] a ; Involved in virulence [68] EnvZ (STY4295) OmpR (STY4294)…”

Development of conjugation-mediated versatile site-specific single-copy luciferase fusion system

“…Ampicillin induced luminescence from Salmonella cpxP-luxCDABE in a CpxR/CpxA-dependent manner but high concentrations of NaCl did not. This is not surprise because ampicillin causes envelope stress (Sailer et al, 2003) and the CpxR/CpxA two-component system is activated by various envelope stresses (Kato et al, 2017;Raivio and Silhavy, 2001). While cpxR and cpxP constitute a head-to-head gene configuration (Danese and Silhavy, 1998), the relative luminescence value from the ∆cpxRA::Cm R cpxP-luxCDABE strain was somewhat higher (5.7-fold) than that from the cpxP-luxCDABE strain even in the non-inducing conditions (i.e.…”