TY - JOUR
T1 - The Role of Zinc Efflux during Acinetobacter baumannii Infection
AU - Alquethamy, Saleh F.
AU - Adams, Felise G.
AU - Naidu, Varsha
AU - Khorvash, Marjan
AU - Pederick, Victoria G.
AU - Zang, Maoge
AU - Paton, James C.
AU - Paulsen, Ian T.
AU - Hassan, Karl A.
AU - Cain, Amy K.
AU - McDevitt, Christopher A.
AU - Eijkelkamp, Bart A.
PY - 2019/10/28
Y1 - 2019/10/28
N2 - 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.
AB - 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.
KW - infection
KW - metal ions
KW - nutrition
KW - pneumonia
KW - transporters
UR - http://www.scopus.com/inward/record.url?scp=85074850419&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/GNT1159752
UR - http://purl.org/au-research/grants/nhmrc/1080784
UR - http://purl.org/au-research/grants/nhmrc/1122582
UR - http://purl.org/au-research/grants/nhmrc/1071659
UR - http://purl.org/au-research/grants/arc/DP170102102
UR - http://purl.org/au-research/grants/nhmrc/1120298
UR - http://purl.org/au-research/grants/arc/FT170100006
U2 - 10.1021/acsinfecdis.9b00351
DO - 10.1021/acsinfecdis.9b00351
M3 - Article
C2 - 31658418
AN - SCOPUS:85074850419
SN - 2373-8227
VL - 6
SP - 150
EP - 158
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 1
ER -