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The Role of Zinc Efflux during Acinetobacter baumannii Infection
journal contribution
posted on 2019-11-08, 19:43 authored by 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. EijkelkampAcinetobacter 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.
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Zinc Effluxzinc deficiencyzinc resistancehost colonizationnovel insightzinc concentrationscation diffusion facilitator transporter CzcDzinc resistance mechanismsmurine modelantibiotic resistancezinc efflux systemssite-specific rolesAcinetobacter baumannii Infection Acinetobacter baumanniimetal efflux system CzcCBAbaumannii infectionbacterium dealstranscriptomic responsesresistance-nodulation-cell divisionimmunocompromised individualsGram-negative bacterium
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