Genomics and Experimental Analysis Reveal a Novel Factor Contributing to the Virulence of Cronobacter sakazakii Strains Associated With Neonate Infection.

Abstract

Cronobacter sakazakii causes meningitis and necrotizing enterocolitis in premature infants. However, its virulence determinants, especially those specific for strains associated with neonate infections, remain largely unknown. In this study, we performed a comparative genomic analysis of 209 C. sakazakii genomes, and 8 clonal groups (CGs) were revealed. CG1 and CG2 were found to be significantly associated with neonate infections, and significantly prevalent genes in these 2 CGs were identified. Of these, a gene encoding the LysR-type regulator, CklR, was shown to contribute to bacterial pathogenicity based on animal experiments. We found that CklR directly binds and activates the suf Fe-S cluster biosynthesis operon, and high expression of the suf operon increases bacterial resistance to oxidative stress, which increases survival within the host. This leads to a high degree of bacteremia, which contributes to the development of meningitis. Our work revealed a novel virulence factor specific to predominant pathogenic C. sakazakii strains.