Small alarmones (p)ppGpp regulate virulence associated traits and pathogenesis ofSalmonella entericaserovar Typhi

• DOI: 10.1111/cmi.13034
• Publication Date: 2019-04-23T16:16:30Z
• Authors: Shreya Dasgupta; Sayan Das; Asim Biswas; Rupak K. Bhadra; Santasabuj Das
• Keywords: Salmonella enterica; Pathogenicity island; Phase variation

How Salmonella enterica serovar Typhi (S. Typhi), an important human pathogen, survives the stressful microenvironments inside gastrointestinal tract and within macrophages remains poorly understood. We report here that S. has a bonafide stringent response (SR) system, which is mediated by (p)ppGpp regulates multiple virulence-associated traits pathogenicity of Ty2 strain. In iron overload mouse model infection, (p)ppGpp0 (Ty2ΔRelAΔSpoT) strain showed minimal systemic spread no mortality, as opposed to 100% death mice challenged with isogenic wild-type Ty2ΔRelAΔSpoT had markedly elongated morphology incomplete septa formation demonstrated severely attenuated motility chemotaxis due loss flagella. Absence Vi-polysaccharide capsule rendered mutant highly susceptible complement-mediated lysis. The phenotypes was contributed transcriptional repression several genes, including fliC, tviA, ftsZ, found reverse transcriptase quantitative polymerase chain reaction gene complementation studies. Finally, reduced invasion into intestinal epithelial cells significantly survival macrophages. To best our knowledge, this first study addressed SR in essential for optimal pathogenic fitness organism.