(p)ppGpp-Dependent Regulation of the Nucleotide Hydrolase PpnN Confers Complement Resistance in Salmonella enterica Serovar Typhimurium

• DOI: 10.1128/iai.00639-20
• Publication Date: 2020-10-30T14:00:52Z
• Authors: N. Y Elizabeth Chau; Deyanira Pérez-Mo...; Wael Elhenawy; Víctor H. Bustamante; Yong E. Zhang; Brian K. Coombes
• Keywords: Salmonella enterica

The stringent response is an essential mechanism of metabolic reprogramming during environmental stress that mediated by the nucleotide alarmones guanosine tetraphosphate and pentaphosphate [(p)ppGpp]. In addition to physiological adaptations, (p)ppGpp also regulates virulence programs in pathogenic bacteria, including Salmonella enterica serovar Typhimurium. S Typhimurium a common cause acute gastroenteritis, but it may spread systemic tissues, resulting severe clinical outcomes. During infection, encounters broad repertoire immune defenses must evade for successful host infection. Here, we examined role resistance complement-mediated killing found synthetase-hydrolase, SpoT, required bacterial survival human serum. We identified hydrolase, PpnN, as target promote fitness Using chromatography mass spectrometry, show PpnN hydrolyzes purine pyrimidine monophosphates generate free nucleobases ribose 5'-phosphate, this activity conferring complement killing. biosynthesis very long O-antigen outer membrane, known be important resistance. Our results provide new insights into mediating evasion innate system bacteria.