Journal article

Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials

Fernando Gordillo Altamirano, John H Forsyth, Ruzeen Patwa, Xenia Kostoulias, Michael Trim, Dinesh Subedi, Stuart K Archer, Faye C Morris, Cody Oliveira, Luisa Kielty, Denis Korneev, Moira K O'Bryan, Trevor J Lithgow, Anton Y Peleg, Jeremy J Barr

NATURE MICROBIOLOGY | NATURE RESEARCH | Published : 2021

Abstract

We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the bacterial capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for capsule biosynthesis, resulting in capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

University of Melbourne Researchers

Grants

Awarded by ARC Australian


Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council


Awarded by Perpetual Trustees Australia award


Funding Acknowledgements

We thank L. Perlaza-Jimenez and R. Dunstan for expert advice in the early stage of this project; the Monash Ramaciotti Cryo-EM platform for the use of facilities; A. Fulcher and A. de Marco for granting access to the SEM; C. Vasconez for feedback regarding the readability, clarity and structure of the manuscript; and D. McCarthy for raw sewage samples for phage isolation. F.G.A. acknowledges the support from Monash University through the Monash Postgraduate Research Scholarships funding his doctoral studies. T.J.L. is an ARC Australian Laureate Fellow (FL130100038). This work, including the efforts of J.J.B., was funded by the Australian Research Council (ARC) Discovery Early Career Researcher Award (DECRA) (DE170100525), National Health and Medical Research Council (NHMRC: 1156588) and the Perpetual Trustees Australia award (2018HIG00007).