{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T10:11:40Z","timestamp":1773396700733,"version":"3.50.1"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["Intramural Research"],"award-info":[{"award-number":["Intramural Research"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Treatment of\n              <jats:italic>Mycobacterium abscessus<\/jats:italic>\n              pulmonary disease requires multiple antibiotics including intravenous \u03b2-lactams (e.g., imipenem).\n              <jats:italic>M. abscessus<\/jats:italic>\n              produces a \u03b2-lactamase (Bla\n              <jats:sub>Mab<\/jats:sub>\n              ) that inactivates \u03b2-lactam drugs but less efficiently carbapenems. Due to intrinsic and acquired resistance in\n              <jats:italic>M. abscessus<\/jats:italic>\n              and poor clinical outcomes, it is critical to understand the development of antibiotic resistance both within the host and in the setting of outbreaks. We compared serial longitudinally collected\n              <jats:italic>M. abscessus<\/jats:italic>\n              subsp.\n              <jats:italic>massiliense<\/jats:italic>\n              isolates from the index case of a cystic fibrosis center outbreak and four outbreak-related strains. We found strikingly high imipenem resistance in the later patient isolates, including the outbreak strain (MIC &gt; 512 \u00b5g\/mL). The phenomenon was recapitulated upon exposure of intracellular bacteria to imipenem. Addition of the \u03b2-lactamase inhibitor avibactam abrogated the resistant phenotype. Imipenem resistance was caused by an increase in \u03b2-lactamase activity and increased\n              <jats:italic>bla<\/jats:italic>\n              <jats:sub>Mab<\/jats:sub>\n              mRNA level. Concurrent increase in transcription of the preceding\n              <jats:italic>ppiA<\/jats:italic>\n              gene indicated upregulation of the entire operon in the resistant strains. Deletion of the porin\n              <jats:italic>mspA<\/jats:italic>\n              coincided with the first increase in MIC (from 8 to 32 \u00b5g\/mL). A frameshift mutation in\n              <jats:italic>msp2<\/jats:italic>\n              responsible for the rough colony morphology and a SNP in ATP-dependent helicase\n              <jats:italic>hrpA<\/jats:italic>\n              cooccurred with the second increase in MIC (from 32 to 256 \u00b5g\/mL). Increased Bla\n              <jats:sub>Mab<\/jats:sub>\n              expression and enzymatic activity may have been due to altered regulation of the\n              <jats:italic>ppiA-bla<\/jats:italic>\n              <jats:sub>Mab<\/jats:sub>\n              operon by the mutated HrpA alone or in combination with other genes described above. This work supports using carbapenem\/\u03b2-lactamase inhibitor combinations for treating\n              <jats:italic>M. abscessus<\/jats:italic>\n              , particularly imipenem-resistant strains.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00673-24","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T13:01:19Z","timestamp":1725973279000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Evolution toward extremely high imipenem resistance in\n            <i>Mycobacterium abscessus<\/i>\n            outbreak strains"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6744-5848","authenticated-orcid":false,"given":"Eva","family":"Le Run","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology (LCIM), Immunopathogenesis Section, National Institute of Allergy and Infectious 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