Triagem de compostos com potencial terapêutico contra Klebsiella pneumoniae multirresistente

Abstract

Bacterial resistance is one of the major threats to society, collapsing public health systems as infections caused by Gram-negative bacteria become increasingly prevalent. Given the lack of efficacious antibiotics capable of addressing these issues, it is crucial to evaluate new treatments for future use. In this context, the study assessed the antimicrobial activity of 240 compounds against a multidrug-resistant (MDR) strain of Klebsiella pneumoniae. The evaluated compounds were selected from the Global Health Priority Box (GHPB) and subjected to assays to determine inhibitory concentration (IC), synergy with polymyxin B (PMB), and toxicity through hemolytic activity evaluation and in vivo assays using the alternative model Caenorhabditis elegans. Four tested compounds (MMV1794211, Diafenthiuron, Fluralaner, and MMV006187), in combination with PMB, demonstrated synergistic antimicrobial activity. Furthermore, these compounds showed low toxicity in hemolytic assays and promising results in the C. elegans model. These findings highlight the potential of MMV1794211, Diafenthiuron, Fluralaner, and MMV006187 as promising candidates for the development of new therapies against multidrug-resistant bacteria.