Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

PLoS Pathogens - Tập 17 Số 2 - Trang e1009291
Yuli Talyansky1, Travis B. Nielsen2,1,3, Jun Yan1, Ulrike MacDonald4, Gisela Di Venanzio5, Somnath Chakravorty4, Amber Ulhaq1, Mario F. Feldman5, Thomas A. Russo4, Evgeny Vinogradov6, Brian Luna1, Meredith S. Wright7, Mark D. Adams8, Brad Spellberg9
1Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, United States of America
2Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
3Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, United States of America
4Division of Infectious Diseases, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Veterans Administration, Buffalo, New York, United States of America
5Department of Molecular Microbiology Washington University School of Medicine, St. Louis, Missouri, United States of America.
6National Research Council Canada, Human Health Therapeutics Centre, Ottawa, Canada
7Rady Children's Institute for Genomic Medicine, San Diego, California, United States of America
8The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America
9LAC+USC Medical Center, Los Angeles, California, United States of America

Tóm tắt

Acinetobacter baumanniiis a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence inA.baumanniiremain uncertain. By comparing genomes among a panel ofA.baumanniistrains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact genegtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenicgtr6mutants, we confirmed thatgtr6-disrupted strains were protected from phagocytosisin vitroand displayed higher bacterial burden and lethalityin vivo.Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illnessin vivo. We found that the CR3 receptor mediated phagocytosis ofgtr6+, but notgtr6-, strains in a complement-dependent manner. Furthermore, hypovirulentgtr6+strains demonstrated increased virulencein vivowhen CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multipleA.baumanniistrains. Thus, capsular structure can determine virulence amongA.baumanniistrains by altering bacterial interactions with host complement-mediated opsonophagocytosis.

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PLoS Pathogens

Tập 17 Số 2

e1009291

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