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In chronic lung infections,\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      populations typically exhibit extensive phenotypic variation, a trait linked to their need to undergo pathoadaptive mutations to counteract host-derived selective pressures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, two clonally related\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      isolates, SCPA07 and SCPA08, were identified to coexist in a single bronchoalveolar lavage fluid (BALF) sample from a patient with bacterial pneumonia. Whole-genome sequencing (WGS) was conducted to characterize their genetic background, as well as antimicrobial resistance and virulence gene profiles. A comprehensive analysis of phylogenetic relationships and comparative genomic features of the two isolates was conducted using a panel of bioinformatics tools. Their antimicrobial resistance mechanisms were elucidated via gene sequence analysis and quantitative reverse-transcription PCR (qRT-PCR). A series of phenotypic experiments, including growth, biofilm formation, environmental stress, and virulence assays, and others were performed to characterize their phenotypic traits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antimicrobial susceptibility assay showed that both strains were carbapenem-non-susceptible (defined as intermediate or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines). Genomic analysis revealed that they are \u2018hypermutator\u2019 strains and harbor both the\n                      <jats:italic>exoS<\/jats:italic>\n                      and\n                      <jats:italic>exoU<\/jats:italic>\n                      virulence genes, indicating an increased propensity for persistent host infection and high virulence potential. Both strains harbored mutations in\n                      <jats:italic>oprD<\/jats:italic>\n                      , and exhibited elevated expression of AmpC \u03b2-lactamase and the efflux pump MexB, which most likely contributed to their non-susceptibility to carbapenems. Despite harboring nucleotide variations at only ten genetic loci, these two strains exhibited distinct phenotypic traits: SCPA07 showed rapid growth, strong biofilm formation, high virulence, and growth advantages under iron limitation and serum stress; in contrast, its variant SCPA08 had slow growth, poor motility, reduced pyocyanin production, low virulence, and increased tolerance to the host antimicrobials human cathelicidin LL-37 and hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ). These phenotypic variations are proposed to be primarily driven by genetic mutations affecting the O-antigen biosynthesis, iron utilization, Porin D, and other determinants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study elucidates the divergent adaptive evolutionary strategies of a single\n                      <jats:italic>exoS<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      \/\n                      <jats:italic>exoU<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      clone within the host during bacterial pneumonia, as well as their critical role in shaping the bacterium\u2019s virulence and adaptability, which sheds light on the within-host evolution dynamics of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      populations during their pathogenesis and persistence in the lung.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-05172-8","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:25:00Z","timestamp":1779085500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of two exoU+\/exoS+ carbapenem-non-susceptible Pseudomonas aeruginosa co-colonizing the lung of a bacterial pneumonia patient"],"prefix":"10.1186","volume":"26","author":[{"given":"Yi","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvxin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"5172_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fcimb.2017.00039","volume":"7","author":"MF Moradali","year":"2017","unstructured":"Moradali MF, Ghods S, Rehm BH. 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