Identification of potential therapeutic antimicrobial peptides against Acinetobacter baumannii in a mouse model of pneumonia

Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy due to their broad-spectrum of antimicrobial activity and low incidence of bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.

Automated summary

Antimicrobial peptides (AMP) are considered an ideal strategy for treating Acinetobacter baumannii-induced pneumonia due to their broad-spectrum antimicrobial activity and low bacterial resistance rates. In a mouse model, two AMPs (SMAP-29 and TP4) showed prophylactic effects, while derivatives of TP4 (dN4 and dC4) exhibited therapeutic activity in inhibiting and eliminating A. baumannii biofilms.