03.07.2025 | Exzellenzcluster „Controlling Microbes to Fight Infections“ (CMFI), Interfakultäres Institut für Mikrobiologie und Infektionsmedizin

Unraveling Bacterial Adaptive Evolution to Innovate Next-Generation Antimicrobial Strategies

Mikrobiologisches Kolloquium

Within-patient selected adaptive mutations have the potential to reveal important insights into bacterial pathogenesis and antibiotic treatment failure. We previously discovered global adaptive evolution of virulence and persistence in multidrug-resistant Klebsiella pneumoniae infections. A detailed mechanistic investigation of adaptive mutations revealed an intrinsic ability of Klebsiella pneumoniae to persist in LAMP1 positive compartments in bladder epithelial cells. Importantly, intracellular infection led to a magnitude increase in antibiotic persistence resulting in an untreatable infection. Targeting these intracellular persisters in a chemical screen led to the discovery of a compound with remarkable broad-spectrum intracellular antimicrobial activity. Ongoing mode of action studies point to a novel antimicrobial strategy involving the induction of a new pathway of cell autonomous immunity. A better understanding of selective pressures in host pathogen systems may not only lead to a better understanding of bacterial pathogenicity and treatment failure but may also inform new approaches to treat bacterial infections.

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