In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075

Citation:

Xia Wu, Juan D Chavez, Devin K Schweppe, Chunxiang Zheng, Chad R Weisbrod, Jimmy K Eng, Ananya Murali, Samuel A Lee, Elizabeth Ramage, Larry A Gallagher, Hemantha D Kulasekara, Mauna E Edrozo, Cassandra N Kamischke, Mitchell J Brittnacher, Samuel I Miller, Pradeep K Singh, Colin Manoil, and James E Bruce. 2016. “In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075.” Nat Commun, 7, Pp. 13414.

Abstract:

The nosocomial pathogen Acinetobacter baumannii is a frequent cause of hospital-acquired infections worldwide and is a challenge for treatment due to its evolved resistance to antibiotics, including carbapenems. Here, to gain insight on A. baumannii antibiotic resistance mechanisms, we analyse the protein interaction network of a multidrug-resistant A. baumannii clinical strain (AB5075). Using in vivo chemical cross-linking and mass spectrometry, we identify 2,068 non-redundant cross-linked peptide pairs containing 245 intra- and 398 inter-molecular interactions. Outer membrane proteins OmpA and YiaD, and carbapenemase Oxa-23 are hubs of the identified interaction network. Eighteen novel interactors of Oxa-23 are identified. Interactions of Oxa-23 with outer membrane porins OmpA and CarO are verified with co-immunoprecipitation analysis. Furthermore, transposon mutagenesis of oxa-23 or interactors of Oxa-23 demonstrates changes in meropenem or imipenem sensitivity in strain AB5075. These results provide a view of porin-localized antibiotic inactivation and increase understanding of bacterial antibiotic resistance mechanisms.
Last updated on 01/15/2019