Coordinate Regulation of Salmonella Virulence Gene Expression During Infection

Salmonella serovars cause a wide variety of diseases ranging from mild gastroenteritis to life threatening systemic infections. An important step during a S. typhimurium infection is the invasion of non-phagocytic epithelial cells. Invasion is mediated by a Type Three Secretion System (TTSS), which is encoded on Salmonella Pathogenicity Island 1 (SPI1). The SPI1 TTSS forms a needle complex through which effector proteins are injected into the cytosol of host cells where they induce engulfment of the bacteria. We identified two regulatory proteins, termed RtsA and RtsB, which are encoded in an operon on an island in S. typhimurium. We show that RtsA increases expression of the invasion genes by inducing hilA expression. RtSA also induces expression of hilD, hilC, invF, and slrP. RtsA induction of these genes is independent of other SPI1 regulators. RtsA directly induces hilA expression by binding to the promoter. We propose that RtsA, HilC and HilD form a feed forward regulatory loop, because each regulator controls expression of rtsA, hilC hilD, and hilA . SirA a regulator of hilA requires HilD to regulate expression of hilC, rtsA, and hilA, consistent with our model. RtsB represses expression of the flagellar genes by binding to the flhDC promoter region. Repression of the positive activators flhDC decreases expression of the entire flagellar regulon. We propose that RtsA and RtsB coordinate induction of invasion and repression of motility in the small intestine. RtsA induces expression of dsbA independent of the SPI1 TTSS and independently of the only known regulator of dsbA, the CpxRA two-component regulatory system. We determined that DsbA is required for the SPI1 TTSS to secrete effector proteins. We also identified gipA as a gene that is specifically induced in the small intestine of the animal. Consistent with the expression profile of gipA, loss of gipA only affects growth or survival in a Peyer's patch. We also determined that a gene located in the B region of Gifsy-1, which we have termed grvB, is an antivirulence gene that is involved in the SodCI-GrvA virulence pathway. GrvB is translocated into the host cytosol in a SPI2 dependent manner.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Ellermeier, Craig Dean

Contributors dc:contributor

• Slauch, James M.

• Biology, Molecular

Language dc:language

eng

Identifier

(MiAaPQ)AAI3086052

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86648