A team of researchers from the University of São Paulo, Brazil has discovered a peptide that has shown promising action against six antibiotic-resistant bacterial pathogens, a development that could lead to urgently needed new treatments against multidrug-resistant (MDR) bacteria.
“The compound we discovered is a new peptide, Pln149-PEP20, with a molecular framework designed to enhance its antimicrobial activity and with low toxicity. The results can be considered promising insofar as the trials involved pathogenic bacteria associated with MDR infections worldwide,” said co-author Adriano Andricopulo, a researcher with The Center for Innovation in Biodiversity and Drug Discovery (CIBFar), a Research, Innovation and Dissemination Center (RIDC) set up and funded by São Paulo Research Foundation (FAPESP).
The study, published in the journal Antibiotics, was led by Ilana Camargo and conducted during the doctoral research of first author Gabriela Righetto at the Molecular Epidemiology and Microbiology Laboratory (LEMiMo) of the University of São Paulo’s São Carlos Institute of Physics (IFSC-USP). The findings build on a decade of research by investigators Leila Baltramini of CIBFar and José Luiz Lopes of the Department of Applied Physics of the Institute of Physics, University of Sao Paulo.
The Baltramini-Lopes group collaboration has studied and analyzed Plantaricin 149 one of a number of plantaricins—substances formed by the bacterium Lactobacillus plantarum to combat other bacteria. Lactobacillus plantarum is a naturally occurring bacteria found in anaerobic plant matter and in many fermented vegetable, meat, and dairy products.
Plantarcin 149 has been well studied over the years and its bactericidal properties have been known for nearly 30 years, first reported by Japanese researchers in 1994. Since then, researchers have sought to find more efficient synthetic analogs. In 2007, a CIBFar team showed that it inhibits the activity of pathogenic bacteria such as Listeria spp. and Staphylococcus spp., which spurred the investigators to search for synthetic analogs that possessed stronger antibacterial activity.
For the current research, Righetto synthesized 20 analogs of Plantaricin 149 and singled out Pln149-PEP20—a peptide half as big as the original—as most effective in the lab.
“The main advances in our research consist of the development of this smaller, more active and less toxic molecule, and the characterization of its action and propensity to develop resistance. It has proven to be highly promising in vitro—active against MDR bacteria and extensively resistant bacteria,” said Camargo, principal investigator for the project.
Based on their results, the researchers will now dive deeper into investigating the peptide’s mechanism of action, to look for potential formulations, and to potentially develop an application for this new molecule. Research is also needed on its cytotoxicity and on its selectivity (whether it affects healthy cells).
“In terms of the action mechanism, it’s also possible to use the cell morphology of the bacteria to identify cellular pathways affected by the peptide,” Righetto noted. “As for optimization, the molecule can be functionalized by being linked to macrostructures, and the amino acid sequence can be modified.”