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Nat Commun. 2016 Nov 11;7:13414. doi: 10.1038/ncomms13414.

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

Author information

1
Department of Genome Sciences, University of Washington, 850 Republican Street, Brotman Building Room 154, Seattle, Washington 98109, USA.
2
Department of Chemistry, University of Washington, Seattle, Washington 98109, USA.
3
Department of Microbiology, University of Washington, Seattle, Washington 98195, USA.
4
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

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.

PMID:
27834373
PMCID:
PMC5114622
DOI:
10.1038/ncomms13414
[Indexed for MEDLINE]
Free PMC Article

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