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

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 researc...

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Autores principales: 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
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Publicado: American Society for Microbiology 2014
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spelling oai:doaj.org-article:1b43211c013b47cab03bc8955db934382021-11-15T15:47:38ZAB5075, 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 Treatments10.1128/mBio.01076-142150-7511https://doaj.org/article/1b43211c013b47cab03bc8955db934382014-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01076-14https://doaj.org/toc/2150-7511ABSTRACT 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.Anna C. JacobsMitchell G. ThompsonChad C. BlackJennifer L. KesslerLily P. ClarkChristin N. McQuearyHanan Y. GanczBrendan W. CoreyJay K. MoonYuanzheng SiMatthew T. OwenJustin D. HallockYoon I. KwakAmy SummersCharles Z. LiDavid A. RaskoWilliam F. PenwellCary L. HonnoldMatthew C. WisePaige E. WatermanEmil P. LeshoRena L. StewartLuis A. ActisThomas J. PalysDavid W. CraftDaniel V. ZurawskiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 3 (2014)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
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
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
description 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.
format article
author 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
author_facet 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
author_sort Anna C. Jacobs
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher American Society for Microbiology
publishDate 2014
url https://doaj.org/article/1b43211c013b47cab03bc8955db93438
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