Scientists have created a potent antibacterial agent that killed drug-resistant microbes and even eradicated stubborn pathogens growing in biofilms, which can be 10 to 1,000 times more tolerant to antibiotics than free-living bacteria. They say the compound, a short protein fragment called SAAP-148, could be a promising drug candidate in the ongoing battle against antibiotic-resistant bacteria. An increasing number of dangerous bacteria are becoming impervious to multiple antibiotics, raising the alarming prospect of untreatable infections killing large numbers of patients. Seeking alternatives to conventional antibiotics, Anna de Breij and colleagues made modified versions of a human antimicrobial peptide called LL-37, which serves as one of the primary innate immune defenses for fighting bacteria by poking holes in their outer membranes. After screening hundreds of peptides for antibacterial activity, de Breij et al. narrowed in on SAAP-148. They showed that SAAP-148 killed several multidrug resistant bacteria belonging to the ESKAPE panel (a pernicious group of pathogens noted by the Infectious Diseases Society of America for their potential to escape antibiotics and cause human harm) without causing resistance. SAAP-148 eliminated bacteria growing in biofilms in culture - even killing the highly resistant populations of so-called "persister cells," which exist in a dormant, drug-tolerant state that can drive the reemergence of infections after antibiotic treatment. What's more, an ointment containing the peptide effectively treated MRSA and Acinetobacter baumannii infected wounds in mice and on samples of ex vivo human skin. A clinical trial to further investigate the ointment is scheduled for 2018, the authors say.
Science Translational Medicine