AB5075, a Highly Virulent Isolate of <named-content content-type="genus-species">Acinetobacter baumannii</named-content>, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments

Anna C. Jacobs; Mitchell G. Thompson; Chad C. Black; Jennifer L. Kessler; Lily P. Clark; Christin N. McQueary; Hanan Y. Gancz; Brendan W. Corey; Jay K. Moon; Yuanzheng Si; Matthew T. Owen; Justin D. Hallock; Yoon I. Kwak; Amy Summers; Charles Z. Li; David A. Rasko; William F. Penwell; Cary L. Honnold; Matthew C. Wise; Paige E. Waterman; Emil P. Lesho; Rena L. Stewart; Luis A. Actis; Thomas J. Palys; David W. Craft; Daniel V. Zurawski

doi:10.1128/mBio.01076-14

mBio (Jul 2014)

AB5075, a Highly Virulent Isolate of <named-content content-type="genus-species">Acinetobacter baumannii</named-content>, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments

Anna C. Jacobs,
Mitchell G. Thompson,
Chad C. Black,
Jennifer L. Kessler,
Lily P. Clark,
Christin N. McQueary,
Hanan Y. Gancz,
Brendan W. Corey,
Jay K. Moon,
Yuanzheng Si,
Matthew T. Owen,
Justin D. Hallock,
Yoon I. Kwak,
Amy Summers,
Charles Z. Li,
David A. Rasko,
William F. Penwell,
Cary L. Honnold,
Matthew C. Wise,
Paige E. Waterman,
Emil P. Lesho,
Rena L. Stewart,
Luis A. Actis,
Thomas J. Palys,
David W. Craft,
Daniel V. Zurawski

Affiliations

Anna C. Jacobs: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Mitchell G. Thompson: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Chad C. Black: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Jennifer L. Kessler: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Lily P. Clark: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Christin N. McQueary: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Hanan Y. Gancz: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Brendan W. Corey: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Jay K. Moon: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Yuanzheng Si: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Matthew T. Owen: Division of Orthopaedics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Justin D. Hallock: Division of Orthopaedics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Yoon I. Kwak: Multidrug-resistant Organism and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Amy Summers: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Charles Z. Li: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
David A. Rasko: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
William F. Penwell: Department of Microbiology, Miami University, Oxford, Ohio, USA
Cary L. Honnold: Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Matthew C. Wise: Department of Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Paige E. Waterman: Multidrug-resistant Organism and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Emil P. Lesho: Multidrug-resistant Organism and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Rena L. Stewart: Division of Orthopaedics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Luis A. Actis: Department of Microbiology, Miami University, Oxford, Ohio, USA
Thomas J. Palys: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
David W. Craft: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
Daniel V. Zurawski: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

DOI: https://doi.org/10.1128/mBio.01076-14
Journal volume & issue: Vol. 5, no. 3

Abstract

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ABSTRACT Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. IMPORTANCE The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.

Published in mBio

ISSN: 2161-2129 (Print); 2150-7511 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/mbio

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