An antimicrobial role for zinc in innate immune defence against group A streptococcus

Ong, Cheryl-lynn Y., Gillen, Christine M., Barnett, Timothy C., Walker, Mark J. and McEwan, Alastair G. (2014) An antimicrobial role for zinc in innate immune defence against group A streptococcus. Journal of Infectious Diseases, 209 10: 1500-1508. doi:10.1093/infdis/jiu053


Author Ong, Cheryl-lynn Y.
Gillen, Christine M.
Barnett, Timothy C.
Walker, Mark J.
McEwan, Alastair G.
Title An antimicrobial role for zinc in innate immune defence against group A streptococcus
Formatted title
An antimicrobial role for zinc in innate immune defence against group A streptococcus
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 1537-6613
0022-1899
Publication date 2014-05-15
Year available 2014
Sub-type Article (original research)
DOI 10.1093/infdis/jiu053
Open Access Status
Volume 209
Issue 10
Start page 1500
End page 1508
Total pages 9
Place of publication Cary, NC, United States
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Background. Zinc plays an important role in human immunity, and it is known that zinc deficiency in the host is linked to increased susceptibility to bacterial infection. In this study, we investigate the role of zinc efflux in the pathogenesis of Streptococcus pyogenes (group A Streptococcus [GAS]), a human pathogen responsible for superficial infections, such as pharyngitis and impetigo, and severe invasive infections.
Methods. The clinically important M1T1 wild-type strain was used in this study, and isogenic mutants were constructed with deletions in the czcD gene (Spy0653; which encodes a putative zinc efflux pump) and adjacent gczA gene (Spy0654; which encodes a putative zinc-dependent activator of czcD).Wild-type, isogenic mutants and complemented strains were tested for resistance against zinc stress, intracellular zinc accumulation, and virulence.
Results. Both czcD and gczA mutants exhibited increased sensitivity to zinc. Transcriptional analyses indicate that GczA upregulates czcD in response to zinc. Both mutants displayed increased susceptibility to human neutrophil killing and reduced virulence in a murine infection model. Furthermore, we showed that neutrophils mobilize zinc in response to GAS.
Conclusions. These data indicate that the innate immune system may use zinc as an antimicrobial agent and that zinc efflux is an important contributor to GAS pathogenesis.
Keyword CzcD
Zinc
Efflux
Group A streptococcus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 15 May 2014, 11:35:32 EST by Christine Gillen on behalf of School of Chemistry & Molecular Biosciences