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oai:repisalud.isciii.es:20.500.12105/138522024-09-27T17:58:29Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608

00925njm 22002777a 4500 dc Vinuesa, Víctor author Cruces Fernández, Raquel author Nonnoi, Francesca author McConnell, Michael J author 2021-05 Infections caused by multidrug-resistant Acinetobacter baumannii would benefit from the development of novel treatment approaches. Compounds that interfere with bacterial iron metabolism, such as iron chelators and gallium nitrate, have previously been shown to have antimicrobial activity against A. baumannii. In this study, we characterize the effect of LpxC inhibitors on the antimicrobial activity of previously characterized iron chelators, 2,2'-bipyridyl (BIP) and deferiprone (DFP), and gallium nitrate (Ga(NO3)3) against A. baumannii reference strains and multidrug-resistant clinical isolates. The LpxC inhibitor LpxC-2 was synergistic with BIP for 30% of strains tested (FICI values: 0.38-1.02), whereas inhibition with LpxC-4 was synergistic with BIP for 60% of strains tested (FICI values: 0.09-0.75). In time-kill assays, combinations of BIP with both LpxC inhibitors demonstrated synergistic activity, with a more than 3 log10 reduction in bacterial counts compared to BIP alone. LpxC-2 was synergistic with Ga(NO3)3 for 50% of strains tested (FICI values: 0.27-1.0), whereas LpxC-4 was synergistic with Ga(NO3)3 for all strains tested (FICI values: 0.08-≤0.50). In time-kill assays, combinations of Ga(NO3)3 with LpxC-2 and LpxC-4 decreased the growth of both strains compared to each compound separately; however, only the combination with LpxC-4 met the defined criteria for synergy. These results identify a novel synergy between two antimicrobial classes against A. baumannii strains. Antibiotics (Basel). 2021 May 20;10(5):609. 10.3390/antibiotics10050609 2079-6382 Antibiotics (Basel, Switzerland) 34065605 http://hdl.handle.net/20.500.12105/13852 LpxC inhibitors Iron chelators Gallium Antibiotic resistance Synergy Inhibition of LpxC Increases the Activity of Iron Chelators and Gallium Nitrate in Multidrug-Resistant Acinetobacter baumannii