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Isolates with resistance to the newest drugs, like ceftazidime\/avibactam (CZA), are increasingly reported. In this study, we analyzed the evolution of KPC-3-producing sequence type (ST) 512\n              <jats:italic>K<\/jats:italic>\n              .\n              <jats:italic>pneumoniae<\/jats:italic>\n              strains isolated at three different times (hospitalization days 45, 56, and 78) from the same patient, two of which were observed in a pericholecystic liver abscess. The three\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              isolates (295Kp, 304Kp, and hmv-318Kp) from the same patient were subjected to antimicrobial susceptibility testing, whole-genome sequencing, sedimentation assay, biofilm measurement, serum resistance assay, macrophage phagocytosis, and adhesion assays. KPC-producing isolate hmv-318Kp exhibited carbapenem susceptibility, hypermucoviscous (hmv) colony phenotype and CZA resistance. Virulence markers of hypervirulent\n              <jats:italic>Klebsiella<\/jats:italic>\n              were absent. Two non-synonymous mutations were identified in the hmv-318Kp genome comparing with isogenic strains: a single-nucleotide polymorphism (SNP) occurred in the pKpQIL plasmid, changing\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>KPC-3<\/jats:sub>\n              in the\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>KPC-31<\/jats:sub>\n              gene variant, conferring CZA resistance; and a second SNP occurred in the\n              <jats:italic>wzc<\/jats:italic>\n              gene of the capsular biosynthesis cluster, encoding a tyrosine kinase, resulting in the F557S Wzc protein mutation. The\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              strain exhibiting an hmv phenotype (hmv-Kp) phenotype has been previously associated with amino acid substitutions occurring in the Wzc tyrosin kinase protein. We observed\n              <jats:italic>in vivo<\/jats:italic>\n              evolution of the ST512 strain to CZA resistance and acquisition of hypermucoviscosity. The pathogenetic role of the detected Wzc substitution is not fully elucidated, but other Wzc mutations were previously reported in hmv\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              . Wzc mutants may be more frequent than expected and an underreported cause of hypermucoviscosity in\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              clinical isolates.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Here we describe the evolution of KPC-3-producing ST512\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              isolated at three different times from the same patient of which the last one, from a biliary abscess, showed CZA resistance by KPC-31 production and manifested hmv colony phenotype. Hypervirulent\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              (hv-Kp) isolates are increasingly reported worldwide. Their hypervirulent traits are associated with the presence of rmpA\/A2 genes and an hmv. In this study, we identified an hmv-Kp that lacked the rmpA-D cluster but showed an amino acid substitution in the Wzc tyrosin kinase protein, involved in the capsular biosynthesis. This hmv-Kp strain emerged\n              <jats:italic>in vivo<\/jats:italic>\n              and evolved resistance to ceftazidime\/avibactam resistance in a liver abscess of a patient. Our findings suggest that wzc mutations may be underreported, making it challenging to distinguish hv-Kp from \u201cclassic\u201d\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              with an hmv phenotype.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00423-24","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T14:36:27Z","timestamp":1724337387000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["<i>In vivo<\/i>\n            evolution to hypermucoviscosity and ceftazidime\/avibactam resistance in a liver abscess caused by\n            <i>Klebsiella pneumoniae<\/i>\n            sequence type 512"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4569-1972","authenticated-orcid":false,"given":"Valerio","family":"Capitani","sequence":"first","affiliation":[{"name":"Department of Public Health 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Umberto I, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy"},{"name":"Clinical Microbiology Unit, University Hospital, Policlinico Umberto I, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Villari","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Teresa","family":"Palamara","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Marzuillo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-6526","authenticated-orcid":false,"given":"Alessandra","family":"Carattoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa431"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-07"},{"key":"e_1_3_6_4_2","first-page":"11663","volume-title":"Proceedings of the National Academy of Sciences","volume":"109","author":"Ehmann DE","year":"2012","unstructured":"Ehmann DE, Jahi\u0107 H, Ross PL, 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