The role of zinc efflux during Acinetobacter baumannii infection

Saleh F. Alquethamy, Felise G. Adams, Varsha Naidu, Marjan Khorvash, Victoria G. Pederick, Maoge Zang, James C. Paton, Ian T. Paulsen, Karl A. Hassan, Amy K. Cain, Christopher A. McDevitt, Bart A. Eijkelkamp

Research output: Contribution to journalArticle

Abstract

Acinetobacter baumannii is a ubiquitous Gram-negative bacterium, that is associated with significant disease in immunocompromised individuals. The success of A. baumannii is partly attributable to its high level of antibiotic resistance. Further, A. baumannii expresses a broad arsenal of putative zinc efflux systems that are likely to aid environmental persistence and host colonization, but detailed insights into how the bacterium deals with toxic concentrations of zinc are lacking. In this study we present the transcriptomic responses of A. baumannii to toxic zinc concentrations. Subsequent mutant analyses revealed a primary role for the resistance-nodulation-cell division heavy metal efflux system CzcCBA, and the cation diffusion facilitator transporter CzcD in zinc resistance. To examine the role of zinc at the host-pathogen interface we utilized a murine model of zinc deficiency and challenge with wild-type and czcA mutant strains, which identified highly site-specific roles for zinc during A. baumannii infection. Overall, we provide novel insight into the key zinc resistance mechanisms of A. baumannii and outline the role these systems play in enabling the bacterium to survive in diverse environments.

Original languageEnglish
Pages (from-to)150-158
Number of pages9
JournalACS Infectious Diseases
Volume6
Issue number1
Early online date28 Oct 2019
DOIs
Publication statusPublished - 10 Jan 2020

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Keywords

  • metal ions
  • nutrition
  • infection
  • transporters
  • pneumonia

Cite this

Alquethamy, S. F., Adams, F. G., Naidu, V., Khorvash, M., Pederick, V. G., Zang, M., ... Eijkelkamp, B. A. (2020). The role of zinc efflux during Acinetobacter baumannii infection. ACS Infectious Diseases, 6(1), 150-158. https://doi.org/10.1021/acsinfecdis.9b00351