| DOI | Resolve DOI: https://doi.org/10.1371/journal.ppat.1002758 |
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| Author | Search for: Iwashkiw, J.A.; Search for: Seper, A.; Search for: Weber, B.S.; Search for: Scott, N.E.; Search for: Vinogradov, E.1; Search for: Stratilo, C.; Search for: Reiz, B.; Search for: Cordwell, S.J.; Search for: Whittal, R.; Search for: Schild, S.; Search for: Feldman, M.F. |
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| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | galactose; glucose; glucuronic acid; glycan; glycoprotein; n acetylglucosamine; pentasaccharide; bacterial protein; glycoprotein; membrane protein; polysaccharide; Acinetobacter baumannii; analytic method; animal experiment; animal model; bacterial genome; bacterial growth; bacterial strain; bacterial virulence; bacterium isolate; bacterium isolation; biofilm; carbon nuclear magnetic resonance; chromatography; Dictyostelium discoideum; galleria mellonella; gene sequence; heteronuclear single quantum coherence; homologous recombination; hospital infection; in vivo study; insect; mass spectrometry; matrix assisted laser desorption ionization time of flight mass spectrometry; protein glycosylation; proton nuclear magnetic resonance; sepsis; tandem mass spectrometry; two dimensional difference gel electrophoresis; zwitterionic hydrophilic interaction chromatography; Acinetobacter infection; Bagg albino mouse; confocal microscopy; gene inactivation; glycosylation; metabolism; mouse; nuclear magnetic resonance spectroscopy; pathogenicity; virulence; Western blotting; Acinetobacter baumannii; Dictyostelium discoideum; Galleria mellonella; Hexapoda; Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; Biofilms; Blotting, Western; Gene Knockout Techniques; Glycoproteins; Glycosylation; Magnetic Resonance Spectroscopy; Mass Spectrometry; Membrane Proteins; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Polysaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Virulence |
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| Abstract | Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening "superbugs" for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics. © 2012 Iwashkiw et al. |
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| Publication date | 2012 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21269237 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | ec6c0bb8-04a0-4b25-8aba-aeb5977f2a8f |
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| Record created | 2013-12-12 |
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| Record modified | 2021-09-17 |
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