Work

A humanized monoclonal antibody potentiates killing of Pseudomonas aeruginosa by common antibiotics

Year: 2026

Type: article

Abstract: OBJECTIVE: Chronic and recurrent cystic fibrosis lung infections, commonly due to the presence of recalcitrant Pseudomonas aeruginosa biofilms, are not effectively cleared with traditional antibiotics, largely due to a structurally sound and protective extracellular DNA matrix that envelopes biofilm-resident bacteria. We recently showed that when extracellular DNA architecture is disrupted by a humanized monoclonal antibody (HuTipMab) directed against the protective epitopes of universal bacterial proteins that serve as linchpins within the lattice (DNABII proteins), resident bacteria are released in a highly sensitive phenotype that renders them vulnerable to killing by host immune effectors and antibiotics. METHODS: P. aeruginosa biofilms formed by 3 clinical isolates were incubated with media alone or HuTipMab to generate non-biofilm-associated bacteria (NBfA) or bacteria newly released from biofilm residence (NRel), respectively. Antibiotic susceptibility testing at sub-MIC concentrations was then performed on each bacterial population to determine the sensitivity of NRel to the action of antibiotics compared to their non-biofilm-associated bacteria counterparts. RESULTS: Biofilms formed by three P. aeruginosa clinical isolates were significantly disrupted by HuTipMab prior to treatment with three commonly prescribed antibiotics for people with cystic fibrosis: colistin, aztreonam, or tobramycin. Bacteria newly released from HuTipMab-treated biofilms were significantly more susceptible to killing by each tested antibiotic compared with both their non-biofilm-associated counterparts and those resident within a biofilm. CONCLUSIONS: Whereas antibiotics alone do not successfully clear P. aeruginosa from lungs with cystic fibrosis, we herein provide support for a novel approach toward the aforementioned goal that both independently targets biofilm infrastructure and empowers the use of traditional antibiotics.

Source: Journal of Global Antimicrobial Resistance

DOI: 10.1016/j.jgar.2026.03.013

Authors: Jaime D. Rhodes, Steven D. Goodman, Lauren O. Bakaletz

Institutions: Nationwide Children's Hospital, Abigail Wexner Research Institute, The Ohio State University

Language: English

Topic: Bacterial biofilms and quorum sensing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,890