TY - JOUR
T1 - The Two-Component System CpxRA Represses Salmonella Pathogenicity Island 2 by Directly Acting on the ssrAB Regulatory Operon
AU - León-Montes, Nancy
AU - Nava-Galeana, Jessica
AU - Rodríguez-Valverde, Diana
AU - Soria-Bustos, Jorge
AU - Rosales-Reyes, Roberto
AU - Rivera-Gutiérrez, Sandra
AU - Hirakawa, Hidetada
AU - Ares, Miguel A.
AU - Bustamante, Víctor H.
AU - De la Cruz, Miguel A.
N1 - Publisher Copyright:
© 2022 León-Montes et al.
PY - 2022/9
Y1 - 2022/9
N2 - The acquisition of Salmonella pathogenicity island 2 (SPI-2) conferred on Salmonella the ability to survive and replicate within host cells. The ssrAB bicistronic operon, located in SPI-2, encodes the SsrAB two-component system (TCS), which is the central positive regulator that induces the expression of SPI-2 genes as well as other genes located outside this island. On the other hand, CpxRA is a two-component system that regulates expression of virulence genes in many bacteria in response to different stimuli that perturb the cell envelope. We previously reported that the CpxRA system represses the expression of SPI-1 and SPI-2 genes under SPI-1-inducing conditions by decreasing the stability of the SPI-1 regulator HilD. Here, we show that under SPI-2- inducing conditions, which mimic the intracellular environment, CpxRA represses the expression of SPI-2 genes by the direct action of phosphorylated CpxR (CpxR-P) on the ssrAB regulatory operon. CpxR-P recognized two sites located proximal and distal from the promoter located upstream of ssrA. Consistently, we found that CpxRA reduces the replication of Salmonella enterica serovar Typhimurium inside murine macrophages. Therefore, our results reveal CpxRA as an additional regulator involved in the intracellular lifestyle of Salmonella, which in turn adds a new layer to the intricate regulatory network controlling the expression of Salmonella virulence genes.
AB - The acquisition of Salmonella pathogenicity island 2 (SPI-2) conferred on Salmonella the ability to survive and replicate within host cells. The ssrAB bicistronic operon, located in SPI-2, encodes the SsrAB two-component system (TCS), which is the central positive regulator that induces the expression of SPI-2 genes as well as other genes located outside this island. On the other hand, CpxRA is a two-component system that regulates expression of virulence genes in many bacteria in response to different stimuli that perturb the cell envelope. We previously reported that the CpxRA system represses the expression of SPI-1 and SPI-2 genes under SPI-1-inducing conditions by decreasing the stability of the SPI-1 regulator HilD. Here, we show that under SPI-2- inducing conditions, which mimic the intracellular environment, CpxRA represses the expression of SPI-2 genes by the direct action of phosphorylated CpxR (CpxR-P) on the ssrAB regulatory operon. CpxR-P recognized two sites located proximal and distal from the promoter located upstream of ssrA. Consistently, we found that CpxRA reduces the replication of Salmonella enterica serovar Typhimurium inside murine macrophages. Therefore, our results reveal CpxRA as an additional regulator involved in the intracellular lifestyle of Salmonella, which in turn adds a new layer to the intricate regulatory network controlling the expression of Salmonella virulence genes.
KW - CpxRA
KW - SPI-2
KW - Salmonella
KW - cpxRA
KW - ssrAB
UR - http://www.scopus.com/inward/record.url?scp=85140856605&partnerID=8YFLogxK
U2 - 10.1128/spectrum.02710-22
DO - 10.1128/spectrum.02710-22
M3 - Artículo
C2 - 36073960
AN - SCOPUS:85140856605
SN - 2165-0497
VL - 10
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 5
ER -