A conserved GTPase YchF of Vibrio vulnificus is involved in macrophage cytotoxicity, iron acquisition, and mouse virulence

Vibrio vulnificus, a highly virulent marine bacterium, causes serious wound infections and fatal septicemia in many areas of the world. To identify V. vulnificus genes required for killing macrophages, we made an insertional mutant library of V. vulnificus and screened it for reduced macrophage cytotoxicity. One mutant defective in macrophage cytotoxicity had an insertion in ychF, a gene encoding a putative GTPase. In addition to reduced cytotoxicity, this mutant had attenuated growth in iron-limited medium and reduced virulence in iron-overloaded mice. The ychF mutation also down-regulated the transcription level of the rtxA1 gene. RtxA1 mutants significantly decreased cytotoxicity to macrophages compared to wild-type bacteria. Overall, these results show that YchF elicits macrophage cytotoxicity through an rtxA1 pathway and is important for mouse virulence.