Biophysical Parameters Involved in Bacteria Resistance to Antimicrobial Peptides

Abstract

The molecular mechanism, by which bacteria sense antimicrobial peptides (AMPs) that promote its virulence is partially known. 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. As a consequence they have the potential to develop resistance to AMPs. In the case of 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. However, it is not yet clear whether this mechanism is shared by AMPs in general, or it requires specific biophysical properties for AMPs such as secondary structure, amino acid composition or specific sequence. Our studies reveal that changing the biophysical properties of a peptide that can induce resistance, such as incorporation of D-amino acids, can improve the peptides activity against Salmonella typhimurium probably by affecting the two component system. Studes along this line suggest that such peptide modifications can be used in order to overcome the inducible resistance of Salmonella typhimurium.