Affiliation:
1. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
2. University of Illinois Urbana-Champaign, Department of Microbiology, Urbana, Illinois, USA
Abstract
ABSTRACT
In bacteria, the intracellular levels of metals are mediated by tightly controlled acquisition and efflux systems. This is particularly true of copper, a trace element that is universally toxic in excess. During infection, the toxic properties of copper are exploited by the mammalian host to facilitate bacterial clearance. To better understand the role of copper during infection, we characterized the contribution of the
cop
operon to copper homeostasis and virulence in
Streptococcus pneumoniae
. Deletion of either the exporter, encoded by
copA
, or the chaperone, encoded by
cupA
, led to hypersensitivity to copper stress. We further demonstrated that loss of the copper exporter encoded by
copA
led to decreased virulence in pulmonary, intraperitoneal, and intravenous models of infection. Deletion of
copA
resulted in enhanced macrophage-mediated bacterial clearance
in vitro
. The attenuation phenotype of the
copA
mutant in the lung was found to be dependent on pulmonary macrophages, underscoring the importance of copper efflux in evading immune defenses. Overall, these data provide insight into the role of the
cop
operon in pneumococcal pathogenesis.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
68 articles.
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