R-pyocin-mediated selection restores aminoglycoside sensitivity in a pan-drug resistant Pseudomonas aeruginosa isolate

R-pyocin selection in the pan-drug-resistant Pseudomonas aeruginosa wound isolate MRSN 6220 repeatedly yielded pyomelanogenic variants with 250–388 kbp chromosomal deletions that restore aminoglycoside sensitivity.

• Why it matters: Conventional antibiotics often fail against pan-drug-resistant Pseudomonas aeruginosa, and there is a need for strategies that can both select resistance to a new agent and simultaneously reverse multidrug resistance.
• What they did: The study applied sustained R-pyocin pressure to PAO1, PAK, and MRSN 6220, then mapped recovered variants; deletions removed galU, hmgA, and mexXYZ, and effects were tested in Galleria mellonella and in murine wound tissue ex vivo with gentamicin.
• The result: All recovered pyomelanogenic variants evaded R-pyocin killing via deletions spanning 250–388 kbp, and gentamicin treatment produced a significant 3-log reduction in bacterial load for the brown mutants, unlike the pan-drug-resistant ancestor.

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