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Title SsrB-dependent regulation during Salmonella pathogenesis
Publication Date
Date Available
Degree PhD
Degree Level doctoral
University/Publisher McMaster University

Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In part, this ability to adapt can be attributed to horizontal gene transfer, a phenomenon which introduces novel genetic information that can be appropriated for use in particular niches. Nowhere is this more relevant than in pathogenic bacteria, whose acquisition of virulence genes have provided an arsenal that permits them to thrive within their selected host. Regulatory evolution is necessary for timely regulation of these acquired virulence genes in the host environment. Salmonella enterica serovar Typhimurium is an intracellular pathogen which possesses numerous horizontally-acquired genomic islands encoding pathogenic determinants that facilitate its host lifestyle. One island, Salmonella Pathogenicity Island (SPI)-2, encodes a type-III secretion system (T3SS) which is regulated by the two-component regulatory system SsrA-SsrB. This system coordinates expression of the SPI-2 T3SS as well as an array of virulence effectors encoded in horizontally-acquired regions throughout the Salmonella genome. The studies presented here investigated the mechanisms in which the transcription factor SsrB functions to integrate virulence processes through regulatory adaptation. This work identified the regulatory logic controlling SsrB and defined the associated SsrB regulon. Furthermore, SsrB was found to induce a regulatory cascade responsible for the expression of bacteriophage genes encoded within SPI-12, an island that also contributes to Salmonella virulence. These findings demonstrate the important contribution of regulatory evolution in pathogen adaptation to the host, and show that horizontally-acquired genes, once integrated into appropriate regulatory networks, can contribute to pathogen fitness in specific niche environments.

Doctor of Philosophy (PhD)

Subjects/Keywords gene regulation; pathogenicity; virulence; type-3 secretion systems; bacteriophage; Biochemistry; Molecular genetics; Pathogenic Microbiology; Biochemistry
Contributors Coombes, Brian K.; Nodwell, Justin; Schellhorn, Herb; Biochemistry
Country of Publication ca
Record ID handle:11375/12775
Other Identifiers opendissertations/7633; 8695; 3548651
Repository mcmaster
Date Retrieved
Date Indexed 2019-01-09

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…and -2 in Salmonella enterica encode a specialized secretion system that facilitates interaction with and manipulation of host cells; the LEE mediates attachment and effacement of gut epithelial cells, while the systems in Salmonella cause invasion…

…and mediate survival of these pathogens in host cells. Many pathogenicity islands also encode genes for virulence effector proteins, fimbriae, toxins, adhesins, as well as other secretion systems that facilitate host manipulation [15]…

…encoding phage [24]. Prophages can carry additional genes that frequently encode virulence factors which contribute to fitness in the host environment [25]. These genes often function as translocated effectors for secretion systems, as…

…fimbrial operons, secretion systems, T3SS-associated effectors, and serotype conversion genes amongst others [71]. Overall, the SPIs have farreaching functions that contribute to the genetic diversity and host specificity of Salmonella serovars…

…comparative studies with conserved components in orthologous systems, its translocon and effector proteins have been extensively investigated both in vitro and in vivo. The structural composition of the secretion apparatus is largely conserved with those…

…diagram of Salmonella Pathogenicity Island-2 ...................... 33 Figure 1.2 Schematic of the SPI-2 type-III secretion system.................................... 35 Figure 1.3 Overview of phage λ regulatory mechanisms for the lysogenic and lytic…

…resistant Salmonella Pathogenicity Island Salmonella Pathogenicity Island-2 Salmonella Pathogenicity Island-12 secretion system apparatus secretion system chaperone secretion system effector secretion system regulator Sodalis glossinidius Sodalis Symbiosis…

…Region-3 Shiga-toxin producing E. coli subspecies serovar thymine type-I secretion system type-III secretion system type-VI secretion system two-component system transcription factor xv tL TLR Tn tR tRNA U v/v W w/v λ   + left terminator Toll-like…