Small alarmones (p)ppGpp regulate virulence associated traits and pathogenesis ofSalmonella entericaserovar Typhi
Mice, Knockout
0301 basic medicine
Mice, Inbred BALB C
Iron Overload
Polysaccharides, Bacterial
Guanosine Pentaphosphate
Gene Expression Regulation, Bacterial
Salmonella typhi
3. Good health
Disease Models, Animal
GTP Pyrophosphokinase
Mice
03 medical and health sciences
RAW 264.7 Cells
Bacterial Proteins
Liver
Host-Pathogen Interactions
Animals
Humans
Caco-2 Cells
Pyrophosphatases
HT29 Cells
Signal Transduction
DOI:
10.1111/cmi.13034
Publication Date:
2019-04-23T16:16:30Z
AUTHORS (5)
ABSTRACT
How Salmonella enterica serovar Typhi (S. Typhi), an important human pathogen, survives the stressful microenvironments inside the gastrointestinal tract and within macrophages remains poorly understood. We report here that S. Typhi has a bonafide stringent response (SR) system, which is mediated by (p)ppGpp and regulates multiple virulence-associated traits and the pathogenicity of the S. Typhi Ty2 strain. In an iron overload mouse model of S. Typhi infection, the (p)ppGpp0 (Ty2ΔRelAΔSpoT) strain showed minimal systemic spread and no mortality, as opposed to 100% death of the mice challenged with the isogenic wild-type strain. Ty2ΔRelAΔSpoT had markedly elongated morphology with incomplete septa formation and demonstrated severely attenuated motility and chemotaxis due to the loss of flagella. Absence of the Vi-polysaccharide capsule rendered the mutant strain highly susceptible to complement-mediated lysis. The phenotypes of Ty2ΔRelAΔSpoT was contributed by transcriptional repression of several genes, including fliC, tviA, and ftsZ, as found by reverse transcriptase quantitative polymerase chain reaction and gene complementation studies. Finally, Ty2ΔRelAΔSpoT had markedly reduced invasion into intestinal epithelial cells and significantly attenuated survival within macrophages. To the best of our knowledge, this was the first study that addressed SR in S. Typhi and showed that (p)ppGpp was essential for optimal pathogenic fitness of the organism.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (69)
CITATIONS (24)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....