AB5075, a highly virulent isolate of acinetobacter baumannii, 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 & 6 others Emil P. Lesho, Rena L. Stewart, Luis A. Actis, Thomas J. Palys, David Craft, Daniel V. Zurawski

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish (US)
JournalmBio
Volume5
Issue number3
DOIs
StatePublished - May 27 2014

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Acinetobacter baumannii
Animal Models
Lung
Open Fractures
State Hospitals
Insertional Mutagenesis
Pulsed Field Gel Electrophoresis
Multiplex Polymerase Chain Reaction
Multiple Drug Resistance
Osteomyelitis
Rifampin
Microbial Drug Resistance
Infection
Research
Libraries
Virulence
Chromosomes
Anti-Bacterial Agents
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Virology

Cite this

Jacobs, A. C., Thompson, M. G., Black, C. C., Kessler, J. L., Clark, L. P., McQueary, C. N., ... Zurawski, D. V. (2014). AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. mBio, 5(3). https://doi.org/10.1128/mBio.01076-14
Jacobs, Anna C. ; Thompson, Mitchell G. ; Black, Chad C. ; Kessler, Jennifer L. ; Clark, Lily P. ; McQueary, Christin N. ; Gancz, Hanan Y. ; Corey, Brendan W. ; Moon, Jay K. ; Si, Yuanzheng ; Owen, Matthew T. ; Hallock, Justin D. ; Kwak, Yoon I. ; Summers, Amy ; Li, Charles Z. ; Rasko, David A. ; Penwell, William F. ; Honnold, Cary L. ; Wise, Matthew C. ; Waterman, Paige E. ; Lesho, Emil P. ; Stewart, Rena L. ; Actis, Luis A. ; Palys, Thomas J. ; Craft, David ; Zurawski, Daniel V. / AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. In: mBio. 2014 ; Vol. 5, No. 3.
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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.",
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Jacobs, AC, Thompson, MG, Black, CC, Kessler, JL, Clark, LP, McQueary, CN, Gancz, HY, Corey, BW, Moon, JK, Si, Y, Owen, MT, Hallock, JD, Kwak, YI, Summers, A, Li, CZ, Rasko, DA, Penwell, WF, Honnold, CL, Wise, MC, Waterman, PE, Lesho, EP, Stewart, RL, Actis, LA, Palys, TJ, Craft, D & Zurawski, DV 2014, 'AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments', mBio, vol. 5, no. 3. https://doi.org/10.1128/mBio.01076-14

AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. / Jacobs, Anna C.; Thompson, Mitchell G.; Black, Chad C.; Kessler, Jennifer L.; Clark, Lily P.; McQueary, Christin N.; Gancz, Hanan Y.; Corey, Brendan W.; Moon, Jay K.; Si, Yuanzheng; Owen, Matthew T.; Hallock, Justin D.; Kwak, Yoon I.; Summers, Amy; Li, Charles Z.; Rasko, David A.; Penwell, William F.; Honnold, Cary L.; Wise, Matthew C.; Waterman, Paige E.; Lesho, Emil P.; Stewart, Rena L.; Actis, Luis A.; Palys, Thomas J.; Craft, David; Zurawski, Daniel V.

In: mBio, Vol. 5, No. 3, 27.05.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments

AU - Jacobs, Anna C.

AU - Thompson, Mitchell G.

AU - Black, Chad C.

AU - Kessler, Jennifer L.

AU - Clark, Lily P.

AU - McQueary, Christin N.

AU - Gancz, Hanan Y.

AU - Corey, Brendan W.

AU - Moon, Jay K.

AU - Si, Yuanzheng

AU - Owen, Matthew T.

AU - Hallock, Justin D.

AU - Kwak, Yoon I.

AU - Summers, Amy

AU - Li, Charles Z.

AU - Rasko, David A.

AU - Penwell, William F.

AU - Honnold, Cary L.

AU - Wise, Matthew C.

AU - Waterman, Paige E.

AU - Lesho, Emil P.

AU - Stewart, Rena L.

AU - Actis, Luis A.

AU - Palys, Thomas J.

AU - Craft, David

AU - Zurawski, Daniel V.

PY - 2014/5/27

Y1 - 2014/5/27

N2 - 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.

AB - 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.

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