Role of Cross Talk in Regulating the Dynamic Expression of the FlagellarSalmonellaPathogenicity Island 1 and Type 1 Fimbrial Genes

Abstract

Salmonella enterica, a common food-borne pathogen, differentially regulates the expression of multiple genes during the infection cycle. These genes encode systems related to motility, adhesion, invasion, and intestinal persistence. Key among them is a type three secretion system (T3SS) encoded within Salmonella pathogenicity island 1 (SPI1). In addition to the SPI1 T3SS, other systems, including flagella and type 1 fimbriae, have been implicated in Salmonella pathogenesis. In this study, we investigated the dynamic expression of the flagellar, SPI1, and type 1 fimbrial genes. We demonstrate that these genes are expressed in a temporal hierarchy, beginning with the flagellar genes, followed by the SPI1 genes, and ending with the type 1 fimbrial genes. This hierarchy could mirror the roles of these three systems during the infection cycle. As multiple studies have shown that extensive regulatory cross talk exists between these three systems, we also tested how removing different regulatory links between them affects gene expression dynamics. These results indicate that cross talk is critical for regulating gene expression during transitional phases in the gene expression hierarchy. In addition, we identified a novel regulatory link between flagellar and type 1 fimbrial gene expression dynamics, where we found that the flagellar regulator, FliZ, represses type 1 fimbrial gene expression through the posttranscriptional regulation of FimZ. The significance of these results is that they provide the first systematic study of the effect of regulatory cross talk on the expression dynamics of flagellar, SPI1, and type 1 fimbrial genes.Salmonella enterica causes a large number of diseases ranging from self-limiting gastroenteritis to life-threatening systemic infection (21, 62). Previous studies have identified multiple factors involved in Salmonella pathogenesis, including those related to motility, adhesion, invasion, and intestinal persistence (12,18,39,43,45,55,66,83,(86)(87)(88). Key among them is a type 3 secretion system (T3SS) encoded within a 40-kb region of the chromosome called Salmonella pathogenicity island 1 (SPI1) (46-48, 51, 63, 76). The SPI1 T3SS functions as a molecular hypodermic needle, enabling Salmonella to inject proteins into host cells (11-13). These injected proteins both commandeer the actin cytoskeleton to facilitate the invasion of host cells and induce inflammatory diarrhea (27,29,33,52,59,92).In addition to the SPI1 T3SS, other systems, including flagella and type 1 fimbriae, have been implicated in Salmonella pathogenesis (31,36,75). Briefly, flagella are long helical filaments attached to rotary motors embedded within the membrane that enable the bacterium to swim in liquids and swarm over surfaces (9). Flagella are thought to facilitate invasion by enabling Salmonella to swim to sites of invasion (39,75). In addition to motility, flagellin activates the expression of proinflammatory cytokines (26,60,61,77,84). Type 1 fimbriae, on the other hand, are hairlike appendages that carry adhesins...

Vibrio cholerae VttR A and VttR B Regulatory Influences Extend beyond the Type 3 Secretion System Genomic Island

“…A33_1527 is similar to the N16961 FrhC protein (VC1621), a flagellum-regulated hemagglutination protein with a TolC (type I secretion outer mem- (35,37). flaA transcription is dependent on 54 and requires an additional regulator, FlrC, which must be phosphorylated as part of a two-component system (FlrBC) in order for the 54 dependent transcription of flaA to proceed. The genes encoding the four minor flagellins are under the transcriptional control of 28 (encoded by fliA), whose activity is controlled by the anti- 28 factor FlgM (35).…”

The fimbriae activator MatA switches off motility in Escherichia coli by repression of the flagellar master operon flhDC

“…To avoid simultaneous expression of motility-enhancing flagella and adhesion-promoting fimbriae, various bacteria, e.g. Proteus mirabilis, Salmonella enterica and E. coli, harbour regulatory systems for reciprocal regulation of these traits (Clegg & Hughes, 2002;Li et al, 2001;Ogasawara et al, 2011;Pesavento et al, 2008;Saini et al, 2010;Simm et al, 2004). We have previously described the common and conserved Mat (meningitis-associated and temperatureregulated) fimbria (Pouttu et al, 2001) [also called ECP (E. coli common pilus); Rendó n et al., 2007], which has host cell-adhesive (Avelino et al, 2010;Blackburn et al, 2009;Lasaro et al, 2009;Rendó n et al, 2007;Saldaña et al, 2009) and biofilm-promoting (Lehti et al, 2010) properties, and is a critical colonization determinant for a probiotic E. coli strain in the intestine of the infant mouse (Lasaro et al, 2009).…”

Mathematical model of flagella gene expression dynamics in Salmonella enterica serovar typhimurium

“…This likely implies that post-secretion, FliZ made from the class 3 transcript is responsible for activation of SPI1 and SPI4 gene expression. The role of FliZ in activating SPI1 and SPI4 gene expression has been previously reported (Chubiz et al 2010;Kage et al 2008;Saini and Rao 2010;Saini et al 2010b).…”

“…Among this, the role of secretion to tune the strength of the various feedback loops is a critical and novel one. From the perspective of Salmonella pathogenesis, further work needs to be done to validate and test predictions from our model, and shed more light on the multi-process control of the Salmonella infection cycle (Clegg and Hughes 2002;Ellermeier and Slauch 2003;Iyoda et al 2001;Saini et al 2010b;Wu et al 2012). …”