Función y mecanismo molecular del sistema regulatorio RcsC-YojN-RcsB en la patogénesis de Salmonella

DELGADO, MONICA ALEJANDRA

Univ. Nacional de Misiones

Conferencia; Planeamiento del Trabajo Científico; 2007

Fac. de Ciencias Exactas, Qcas y Nat.-Univ. Nacional de Misiones

Salmonella are pathogenic bacteria that affect humans and animals. Salmonella enterica serovar Typhimurium causes a typhoid-like disease in mice, which is used as a model for the disease caused by the human adapted serovar Typhi (1). Bacterial pathogens must modulate their gene expression in order to survive the hostile environments faced during the course of infection. This adaptive response is often mediated by two component regulatory systems. A typical two-component system consists of a sensor kinase that responds to particular stimuli by modifying the phosphorylated state of a cognate regulatory protein (2). Previous work has revealed that a large number of genes, involved in the cell surface biosynthesis, are regulated by several regulatory systems in response to specific environmental signals. One of these regulatory components is the RcsC/YojN/RcsB system, composed of the sensor RcsC, the response regulator RcsB, and the histidine-containing phosphotransfer protein YojN which is apparently used as an intermediary in the phosphoryl transfer from RcsC to RcsB (3). In Salmonella, the RcsC/YojN/RcsB is activated by condition or mutations that alter the cell envelope, such as mutation in tolB (4), in  pmrA mutant (growing in the presence of low Mg2+ and Fe3+) (5) or in rcsC (the rcsC11 constitutive allele) (6); as well as the growth of bacteria on solid surface (our unpubl. result). The activation of this system results in the induction of genes involved in the cellular enveloped synthesis like the cps operon, required for the exopolysaccharide production; and the ugd gene, encoding the UDP-D-glucose dehydrogenase enzyme; and in the repression flhDC operon, to flagella biosynthesis. In the previous report, we demonstrated that expression of RcsB-regulated genes resulting from the overproduction of the RcsB protein, is due to a phosphorylation of RcsB by RcsC-P or YojN-P in a simple step (Fig.1B and C) in addition to the previously characterized multistep pathway (Fig. 1A) (3). We also found that the RcsC protein, but not YojN, is required for cps induction resulting from RcsB overproduction in an ack mutant, which accumulate acetyl-phosphate. Here, RcsC to phosphorylated RcsB can use this acetyl-phosphate as a phosphoryl group donor. This result are according with the hypothesis that in some Rcs system induction conditions, only RcsC or YojN, but not both, are required to RcsB phosphorylation. The RcsC/YojN/RcsB system has also been implicated in Salmonella virulence because mutations of rcsB derepresses transcription of the invasion genes sipB, iagA and invF in the serovar Typhi (7) but prevents transcription of the Typhi-specific Vi antigen, which is required for bacterial spread in the reticuloendothelial system (8-10). In addition, mutation of the rcsC gene (rcsC11) in the serovar Typhimurium attenuated the virulence for mice even when inoculated by the intraperitoneal route (11). This is puzzling because the rcsC mutant is not defective for survival within macrophages (11), which constitutes the site of bacterial replication during systemic infection (12, 13), and because the serovar Typhimurium lacks the Vi antigen.