Hemolysin III drives neuroinvasion and meningitis while impacting desiccation resilience in <i>Cronobacter sakazakii</i>

The ability of <i>Cronobacter sakazakii</i> to cause severe neonatal infections, particularly meningitis, presents a significant public health concern, yet the molecular mechanisms that enable its neuroinvasion remain poorly understood. In this study, we identify Hemolysin III (Hly III), encoded by the ESA_00432 gene, as a key factor in the bacterium's ability to cross the blood-brain barrier (BBB) and initiate meningitis. Our findings demonstrate that Hly III is essential for efficient invasion of human brain microvascular endothelial cells (HBMECs) and subsequent brain colonization in a rat model, underscoring its critical role in neurotropism. Furthermore, we show that the absence of Hly III results in enhanced environmental resilience, as indicated by increased desiccation resistance and hydrophilicity. This metabolic trade-off between virulence and environmental adaptability reveals a novel aspect of <i>C. sakazakii</i>'s pathogenesis and survival strategies. These insights open new avenues for developing targeted interventions to prevent neonatal meningitis and enhance food safety measures against this opportunistic pathogen.