Chapter 21 : : Regulation of Gene Expression, Intracellular Trafficking, and Subversion of Host Defenses

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is a gram-negative coccobacillus that is found in diverse environments, including animal, protozoan, and insect hosts. Several animal models have been used for the study of infection, primarily rodents (including mice, rats, and guinea pigs) as well as rabbits. For all the obvious reasons, the majority of studies have been carried out in mouse models. The host response can be unique regarding infection. This can be largely due to the different in vivo environments this bacterial pathogen encounters during infection (e.g., temperature changes when is transmitted from arthropods to mammals). Production of reactive oxygen species and reactive nitrogen species is an essential innate immune defense mechanism against invading microorganisms. There are four known major regulators of virulence in : MglA, SspA, PmrA, and FevR, which positively control the expression of pathogenicity island (FPI) genes. Each of these proteins also regulates the expression of genes outside the FPI. Capsular polysaccharides are important factors in bacterial pathogenesis and have been the target of a number of successful vaccines. Mutations in LVS and , which are similar to capsule genes, had no effect on capsule expression.

Citation: Mohapatra N, Dai S, Gunn J. 2013. : Regulation of Gene Expression, Intracellular Trafficking, and Subversion of Host Defenses, p 402-421. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch21
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Phagocytosis, intracellular trafficking, and host immune responses during infection of host macrophages. enters host cells by utilizing different receptors. It resides in FCPs transiently after phagocytosis and escapes into the host cell cytosol shortly after infection. In the host cytosol, replicates to high numbers before inducing pyroptosis and apoptosis. FPI-encoded IglC, an important player in phagosomal escape and intracellular replication, is able to activate Ras and inhibit caspase-3 activation. The host cell detects cytosolic by AIM2 or pyrin inflammasomes and leads to IL-1β and IL-18 maturation and secretion. is recognized by the TLR2 signaling pathway at the cell surface and also while within phagosomes, followed by activation of MAPK and NF-κB pathways and proinflammatory cytokine production. is unique in its ability to suppress host immune responses by inhibiting MAPK activation through either a bacterial factor, RipA, host MAPK phosphatase (MKP-1), or other unknown mechanisms. Specific to lowvirulence , but not the highly virulent Schu S4, is the increased level of miR-155, which downregulates SHIP-1, a negative regulator of the PI3K/Akt pathway, and results in high levels of proinflammatory responses. In addition, AcpA can also dephosphorylate NADPH oxidase components and contribute to respiratory burst suppression following infection. doi:10.1128/9781555818524.ch21f1

Citation: Mohapatra N, Dai S, Gunn J. 2013. : Regulation of Gene Expression, Intracellular Trafficking, and Subversion of Host Defenses, p 402-421. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch21
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Figure 2

virulence factors and regulation of virulence genes. The TCS sensor kinase KdpD is phosphorylated due to unknown environmental signals and phosphorylates the response regulator PmrA, allowing PmrA to bind to the promoter regions of different target genes. PmrA binding recruits the MglA-SspA complex or MglA-SspA-RNAP, helping to initiate transcription. In the presence of the alarmone ppGpp, FevR binds to MglA-SspA to form a complex and FevR expression requires PmrA, MglA, SspA, and MigR. However, PmrA, MglA, SspA, and FevR regulate many additional genes outside of the FPI. Hfq regulates protein expression under various external conditions (e.g., peroxide, temperature, salt, and detergent) and inhibits regulation of the operon of the FPI. More studies are required in the future to better understand the role of Hfq in aiding sRNAs to control virulence gene regulation. spp. secrete several proteins (e.g., AcpA, GroEL, KatG, PepO, SodB, and IglA, plus 26 more hypothetical proteins) in culture supernatants. The capsule and LPS have proved to be only mildly antigenic and to induce proinflammatory cytokines. doi:10.1128/9781555818524.ch21f2

Citation: Mohapatra N, Dai S, Gunn J. 2013. : Regulation of Gene Expression, Intracellular Trafficking, and Subversion of Host Defenses, p 402-421. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch21
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