Our lab investigates antimicrobial peptide (AMP) antimicrobial activity towards Gram-negative pathogens. AMPs have the unique ability to target the Gram-negative bacterial membrane, which is a limiting factor for cell penetration by small molecule antibiotics.

 

We are currently investigating mammalian proline-rich AMPs due to their non-lytic membrane interactions and dual targeting of the membrane and ribosome. Proline-rich AMPs hijack the bacterial SbmA transporter to enter the cytosol and interfere with cytosolic processes. Mammalian proline-rich AMPs also translocate through the bacterial membrane which allows for activity in the absence of the SbmA transporter compared to insect proline-rich AMPs that quickly become inactive when the bacteria mutate the transporter.

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We found that the membrane interactions of mammalian proline-rich AMPs vary based on the Klebsiella pneumoniae isolate being tested and with sequence variation between proline-rich AMP orthologs produced by cows and pigs. We hope to learn more about the consequences of non-lytic peptide membrane interactions as they are more suitable for therapeutic approaches due to the host associated cytotoxicity that is encountered when the bacterial cell lyses and releases toxic PAMPs that trigger an overactive immune response.