Crystal structures of YeiE from Cronobacter sakazakii and the role of sulfite tolerance in gram-negative bacteria

Abstract

Cronobacter sakazakii is an emerging gram-negative pathogenic bacterium that causes meningitis, bacteremia, and necrotizing enterocolitis in infants and has a high mortality rate. The YeiE homolog (gpESA_01081) was identified as a global virulence regulator of bacterial pathogenesis in C. sakazakii. YeiE is a LysR-type transcriptional regulator (LTTR) composed of a DNA binding domain and a regulatory domain to recognize the unknown ligand. To reveal the molecular mechanism and function of YeiE, we determined the crystal structure of the regulatory domain of YeiE. A sulfite ion was bound at the putative ligand-binding site, and subsequent studies revealed that the sulfite is the physiological ligand for YeiE. Structural comparisons to its sulfite-free structure further showed the sulfite-dependent conformational change of YeiE. The essential role of YeiE in defending against toxicity from sulfite during the growth of C. sakazakii and Escherichia coli was examined. Furthermore, the target genes and functional roles of YeiE in H2S production and survival capability from neutrophils were investigated. Our findings provide insights into the sophisticated behaviors of pathogenic gram-negative bacteria in response to sulfite from the environment and host.