{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:53:04Z","timestamp":1792284784024,"version":"4.4.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T00:00:00Z","timestamp":1345507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,8,31]],"date-time":"2012-08-31T00:00:00Z","timestamp":1346371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2012,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A critical feature of a potential antimicrobial target is the characteristic of being essential for growth and survival during host infection. For bacteria, genome-wide essentiality screens are usually performed on rich laboratory media. This study addressed whether genes detected in that manner were optimal for the identification of antimicrobial targets since the\n                    <jats:italic>in vivo<\/jats:italic>\n                    milieu is fundamentally different. Mutant derivatives of a clinical isolate of\n                    <jats:named-content content-type=\"genus-species\">Acinetobacter baumannii<\/jats:named-content>\n                    were screened for growth on human ascites, an\n                    <jats:italic>ex vivo<\/jats:italic>\n                    medium that reflects the infection environment. A subset of 34 mutants with unique gene disruptions that demonstrated little to no growth on ascites underwent evaluation in a rat subcutaneous abscess model, establishing 18 (53%) of these genes as\n                    <jats:italic>in vivo<\/jats:italic>\n                    essential. The putative gene products all had annotated biological functions, represented unrecognized or underexploited antimicrobial targets, and could be grouped into five functional categories: metabolic, two-component signaling systems, DNA\/RNA synthesis and regulation, protein transport, and structural. These\n                    <jats:italic>A.\u00a0baumannii in vivo<\/jats:italic>\n                    essential genes overlapped poorly with the sets of essential genes from other Gram-negative bacteria catalogued in the Database of Essential Genes (DEG), including those of\n                    <jats:named-content content-type=\"genus-species\">Acinetobacter baylyi<\/jats:named-content>\n                    , a closely related species. However, this finding was not due to the absence of orthologs. None of the 18\n                    <jats:italic>in vivo<\/jats:italic>\n                    essential genes identified in this study, or their putative gene products, were targets of FDA-approved drugs or drugs in the developmental pipeline, indicating that a significant portion of the available target space within pathogenic Gram-negative bacteria is currently neglected.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The human pathogen\n                    <jats:named-content content-type=\"genus-species\">Acinetobacter baumannii<\/jats:named-content>\n                    is of increasing clinical importance, and a growing proportion of isolates are multiantimicrobial-resistant, pan-antimicrobial-resistant, or extremely resistant strains. This scenario is reflective of the general problem of a critical lack of antimicrobials effective against antimicrobial-resistant Gram-negative bacteria, such as\n                    <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n                    ,\n                    <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n                    ,\n                    <jats:italic>Enterobacter<\/jats:italic>\n                    sp., and\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    . This study identified a set of\n                    <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n                    genes that are essential for growth and survival during infection and demonstrated the importance of using clinically relevant media and\n                    <jats:italic>in vivo<\/jats:italic>\n                    validation while screening for essential genes for the purpose of developing new antimicrobials. Furthermore, it established that if a gene is absent from the Database of Essential Genes, it should not be excluded as a potential antimicrobial target. Lastly, a new set of high-value potential antimicrobial targets for pathogenic Gram-negative bacteria has been identified.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00113-12","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T23:23:26Z","timestamp":1345677806000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["<i>In Vivo<\/i>\n                    -Validated Essential Genes Identified in Acinetobacter baumannii by Using Human Ascites Overlap Poorly with Essential Genes Detected on Laboratory Media"],"prefix":"10.1128","volume":"3","author":[{"given":"Timothy C.","family":"Umland","sequence":"first","affiliation":[{"name":"Hauptman-Woodward Medical Research Institute, Buffalo, New York, USA"},{"name":"Departments of Structural Biology, University at Buffalo, State University of New York, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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