Journal article
Identification of an Acinetobacter baumannii Zinc Acquisition System that Facilitates Resistance to Calprotectin-mediated Zinc Sequestration
PLoS pathogens, Vol.8(12), pp.e1003068-e1003068
12/01/2012
DOI: 10.1371/journal.ppat.1003068
PMCID: PMC3516566
PMID: 23236280
Abstract
Acinetobacter baumannii is an important nosocomial pathogen that accounts for up to 20 percent of infections in intensive care units worldwide. Furthermore, A. baumannii strains have emerged that are resistant to all available antimicrobials. These facts highlight the dire need for new therapeutic strategies to combat this growing public health threat. Given the critical role for transition metals at the pathogen-host interface, interrogating the role for these metals in A. baumannii physiology and pathogenesis could elucidate novel therapeutic strategies. Toward this end, the role for calprotectin- (CP)-mediated chelation of manganese (Mn) and zinc (Zn) in defense against A. baumannii was investigated. These experiments revealed that CP inhibits A. baumannii growth in vitro through chelation of Mn and Zn. Consistent with these in vitro data, Imaging Mass Spectrometry revealed that CP accompanies neutrophil recruitment to the lung and accumulates at foci of infection in a murine model of A. baumannii pneumonia. CP contributes to host survival and control of bacterial replication in the lung and limits dissemination to secondary sites. Using CP as a probe identified an A. baumannii Zn acquisition system that contributes to Zn uptake, enabling this organism to resist CP-mediated metal chelation, which enhances pathogenesis. Moreover, evidence is provided that Zn uptake across the outer membrane is an energy-dependent process in A. baumannii. Finally, it is shown that Zn limitation reverses carbapenem resistance in multidrug resistant A. baumannii underscoring the clinical relevance of these findings. Taken together, these data establish Zn acquisition systems as viable therapeutic targets to combat multidrug resistant A. baumannii infections.
Details
- Title: Subtitle
- Identification of an Acinetobacter baumannii Zinc Acquisition System that Facilitates Resistance to Calprotectin-mediated Zinc Sequestration
- Creators
- M. Indriati Hood - Vanderbilt UniversityBrittany L. Mortensen - Vanderbilt UniversityJessica L. Moore - Vanderbilt UniversityYaofang Zhang - Vanderbilt UniversityThomas E. Kehl-Fie - Vanderbilt UniversityNorie Sugitani - Vanderbilt UniversityWalter J. Chazin - Vanderbilt UniversityRichard M. Caprioli - Vanderbilt UniversityEric P. Skaar - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.8(12), pp.e1003068-e1003068
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.ppat.1003068
- PMID
- 23236280
- PMCID
- PMC3516566
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Number of pages
- 17
- Grant note
- R56AI091771 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA International Student Research Fellowship through Howard Hughes Medical Institute T32GM008320 / Vanderbilt Chemical Biology Interface training program American Heart Association 8P41GMI03391-2 / NIH/NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32 GM07347 / Public Health Service award from the National Institute of General Medical Studies
- Language
- English
- Date published
- 12/01/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618520402771
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