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

Abstract

Background: 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.

Methods: In this study, we performed a comparative genomic analysis of 209 C. sakazakii genomes, and 8 clonal groups (CGs) were revealed.

Results: 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.

Conclusions: Our work revealed a novel virulence factor specific to predominant pathogenic C. sakazakii strains.

Keywords: Cronobacter sakazakii; bacterial virulence; comparative genomics; neonate infection; regulator.