Interkingdom crosstalk: host neuroendocrine stress hormones drive the hemolytic behavior of Salmonella typhi

The ability of bacterial pathogens to sense their immediate environment plays a significant role on their capacity to survive and cause disease. Salmonella enterica serovar typhi (S. typhi) is an exclusively human pathogen that causes typhoid fever. In a recent study, we have shown that S. typhi senses and responds to host neuroendocrine stress hormones to release the toxin hemolysin E. Hormone-mediated hemolysis by S. typhi was inhibited by the β-blocker propranolol and was dependent on the presence of the CpxAR signal transduction system. Furthermore, we demonstrate that normal expression of the small RNA micA is necessary for the arbitration of the response to host  neuroendocrine hormones. This leads to a significant decrease in the levels of the outer membrane protein OmpA and increased formation of membrane vesicles containing HlyE. The exploration of host pathogen interactions is  of paramount importance in deciphering pathogen virulence and the discovery of novel treatments.