{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:56:24Z","timestamp":1783983384490,"version":"3.55.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Newton-Mosharafa Institutional Links","award":["351952191"],"award-info":[{"award-number":["351952191"]}]},{"DOI":"10.13039\/501100000308","name":"British Council UK","doi-asserted-by":"crossref","award":["30863"],"award-info":[{"award-number":["30863"]}],"id":[{"id":"10.13039\/501100000308","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science, Technology, and Innovation Funding Authority"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids\/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jambio\/lxae100","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T02:59:12Z","timestamp":1713322752000},"source":"Crossref","is-referenced-by-count":7,"title":["Dihydrophenazine: a multifunctional new weapon that kills multidrug-resistant <i>Acinetobacter baumannii<\/i> and restores carbapenem and oxidative stress susceptibilities"],"prefix":"10.1093","volume":"135","author":[{"given":"Norhan H","family":"Mahdally","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University , Cairo 11562 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham A","family":"ElShiekh","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University , Cairo 11562 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bathini","family":"Thissera","sequence":"additional","affiliation":[{"name":"School of Computing, Engineering and Physical Sciences, University of the West of Scotland , Paisley PA1 2BE , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Eltaher","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Research Program, Basic Research Department, Children's Cancer Hospital , Cairo 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Cairo 11562 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Magdeldin","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Research Program, Basic Research Department, Children's Cancer Hospital , Cairo 57357 , Egypt"},{"name":"Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University , Ismailia 41522 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-1674","authenticated-orcid":false,"given":"Ali M","family":"El\u00a0Halawany","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University , Cairo 11562 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-2687","authenticated-orcid":false,"given":"Mostafa E","family":"Rateb","sequence":"additional","affiliation":[{"name":"School of Computing, Engineering and Physical Sciences, 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