Identification of a General O-linked Protein Glycosylation System in Acinetobacter baumannii and Its Role in Virulence and Biofilm Formation

PLoS Pathogens

Jeremy A. Iwashkiw¹  Brent S. Weber¹  Nichollas E. Scott¹  Stuart J. Cordwell²  Stefan Schild²  Bela Reiz³  Mario F. Feldman⁴  Andrea Seper⁴  Chad Stratilo⁵  Randy Whittal⁶  Evgeny Vinogradov⁶ 

[1] Alberta Glycomics Centre, Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada;Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada;Defence Research and Development Canada Suffield, Medicine Hat, Alberta, Canada;Institut fuer Molekulare Biowissenschaften, Karl-Franzens-Universitaet Graz, Graz, Austria;Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada;School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales, Australia

关键词: Glycosylation;    Acinetobacter baumannii;    Biofilms;    Glycoproteins;    Antibiotic resistance;    Dictyostelium discoideum;    Acinetobacter;    Amoebas;   

DOI  :  10.1371/journal.ppat.1002758

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY