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We identified a reservoir of\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  variants lacking expression of the H3-T6SS in patients with chronic but not acute pneumonia. A PAO1 \u0394H3-T6 mutant caused increased infection in the murine lung as compared to the wild-type strain. The \u0394H3 mutants exhibited increased transcription of genes involved in phagocytic uptake and respiration under conditions found in the phagolysosome, namely low O\n                  <jats:sub>2<\/jats:sub>\n                  , low pH and abundant itaconate. We confirmed increased intraphagocytic residence of the \u0394H3 mutants and colocalization with LAMP1 within the phagolysosome of both bone marrow derived macrophages\n                  <jats:italic>in vitro<\/jats:italic>\n                  and in alveolar macrophages harvested directly from infected lungs. Persistence within macrophages required itaconate which preserved the viability of infected macrophages and boosted bacterial bioenergetics to optimize consumption of available carbon sources. Our findings demonstrate that selection for loss of H3-T6SS loss of function mutations promotes the metabolic versatility that enables\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  to cause intractable pulmonary infection.\n                <\/jats:p>","DOI":"10.64898\/2026.03.11.711069","type":"posted-content","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:10:33Z","timestamp":1773450633000},"source":"Crossref","is-referenced-by-count":0,"title":["T6SS mutants exploit itaconate to support infection of phagocytes"],"prefix":"10.64898","author":[{"given":"Ayesha Z.","family":"Beg","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Columbia University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanche L.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University, New York, NY, 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