Pseudomonas aeruginosa colonizes the lungs of people with cystic fibrosis, dominates non-healing wounds and burns, and is a leading cause of ventilator-associated pneumonia. The CDC lists it as a critical threat. Multi-drug-resistant strains are now routinely isolated for which few or no antibiotics remain effective. We work on what to do about that.

Precision antimicrobials. Can we kill a resistant strain without destroying everything around it?
R-pyocins are protein nanomachines that P. aeruginosa uses to kill competing strains of its own species. They kill by recognizing a surface receptor rather than by broad metabolic disruption, which means they can be aimed at a specific pathogen while leaving the surrounding microbiota intact. We are defining which clinical strains are susceptible to which R-pyocin types, testing purified R-pyocins in chronic infection models, and engineering retargetable versions whose tail fibers can be swapped to reach new receptors and new species.

Turning resistance into a vulnerability.
Bacteria that escape one selective pressure usually pay for it elsewhere. We map the genetic changes that let P. aeruginosa evade R-pyocins, and the collateral weaknesses those changes create; including re-sensitization to antibiotics. The aim is combination strategies where every available escape route costs the pathogen something we can exploit.

Why treatments fail? Why does a susceptible result in the lab so often not predict what happens in the patient?
Chronic infections are often not clonal. We characterize the genomic and phenotypic diversity within single-patient P. aeruginosa populations and ask how that heterogeneity drives biofilm formation, virulence and treatment failure. This bears directly on the limits of standard susceptibility testing and on how new agents should be evaluated.

Underpinning science: cooperation and conflict.
P. aeruginosa coordinates much of its virulence through quorum sensing and depends on secreted public goods that are shared, costly and vulnerable to cheating. This has been a thread in the lab since its beginning, and it is the reason we can ask the questions above at all. Therapeutic work rests on understanding these behaviors properly rather than on treating bacteria as isolated cells. We continue to pursue it as important fundamental science.

How we work.
Our work is grounded in a collection of P. aeruginosa clinical isolates, which lets us test ideas against the diversity of strains actually encountered in patients rather than against a laboratory reference strain. We combine whole-genome sequencing with population-level phenotyping to characterize those isolates, and utilize ex vivo systems to test candidate treatments under conditions that approximate infection. We express and purify our own R-pyocins in-house, which allows us to control dose, purity and formulation across all of this work. We collaborate closely with clinical partners and colleagues at GTRI.