Bacterial Response to Innate Immunity Host‐Defense Peptides: Parameters Involved in Pathogen Resistance and Specificity

Abstract

Pathogenic bacteria are capable of changing the expression of virulence genes essential to survival and replication, by sensing changes in their microenvironment within the tissues of their host. In the case of some pathogenic bacteria, such as Salmonella typhimurium, some of the virulence genes are controlled by the two component regulatory system, PhoP/PhoQ. The sensor protein of this system, PhoQ, is directly activated by antimicrobial peptides (AMPs). PhoQ phosporylates and activates PhoP, a transcriptional regulatory protein, which in turn activates or represses over 40 different genes. The activation of these genes was found to be essential to the survival of these pathogenic bacteria within the host macrophages. The molecular mechanism by which the bacteria sense AMPs that promote its virulence, was discovered lately. However, it is not yet clear whether this mechanism is induced by specific AMPs or alternatively by AMPs in general. Interestingly, We found that several modifications, such as incorporation of D-amino acids to the AMPs, can improve the peptides activity against Salmonella typhimurium probably by affecting the two component system. These results suggests that such peptide modifications can be used in order to overcome the inducible resistance of Salmonella typhimurium.