Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection
Abstract
Iron is an essential nutrient for bacterial pathogenesis, but in the host, iron is tightly sequestered, limiting its availability for bacterial growth. Although this is an important arm of host immunity, most studies examine how bacteria respond to iron restriction in laboratory rather than host settings, where the microbiome can potentially alter pathogen strategies for acquiring iron. One of the most important transcriptional regulators controlling bacterial iron homeostasis is Fur. Here we used a combination of RNA-seq and chromatin immunoprecipitation (ChIP)-seq to characterize the iron-restricted and Fur regulons of the biofilm-forming opportunistic pathogen Aggregatibacter actinomycetemcomitans. We discovered that iron restriction and Fur regulate 4% and 3.5% of the genome, respectively. While most genes in these regulons were related to iron uptake and metabolism, we found that Fur also directly regulates the biofilm-dispersing enzyme Dispersin B, allowing A. actinomycetemcomitans to escape from iron-scarce environments. We then leveraged these datasets to assess the availability of iron to A. actinomycetemcomitans in its primary infection sites, abscesses and the oral cavity. We found that A. actinomycetemcomitans is not restricted for iron in a murine abscess mono-infection, but becomes restricted for iron upon co-infection with the oral commensal Streptococcus gordonii. Furthermore, in the transition from health to disease in human gum infection, A. actinomycetemcomitans also becomes restricted for iron. These results suggest that host iron availability is heterogeneous and dependent on the infecting bacterial community.
Additional Information
© 2016 Stacy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: September 22, 2016; Accepted: November 21, 2016; Published: December 14, 2016. Editor: Alan R. Hauser, Northwestern University, UNITED STATES. This work was supported by National Institutes of Health Grants R01DE023193 (to MW) and F31DE024931 (to AS). MW is a Burroughs Wellcome Investigator in the Pathogenesis of Infectious Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Bryan Davies for assistance with the ChIP procedure, Dr. Daniel Cornforth for assistance with assembling the A. actinomycetemcomitans 624 genome, and Dr. Kendra Rumbaugh for assistance with the abscess infections. Author Contributions Conceptualization: AS MW. Data curation: AS. Formal analysis: AS. Funding acquisition: AS MW. Investigation: AS NA PJ. Methodology: AS NA PJ MW. Project administration: MW. Resources: AS MW. Software: AS. Supervision: MW. Validation: AS MW. Visualization: AS. Writing – original draft: AS. Writing – review & editing: AS MW. Data Availability: All RNA-seq and ChIP-seq files are available from the National Center for Biotechnology Information Sequence Read Archive (accession numbers SRP081045 and SRP093165). The authors have declared that no competing interests exist.Attached Files
Published - journal.ppat.1006084.pdf
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Additional details
- PMCID
- PMC5156373
- Eprint ID
- 74376
- Resolver ID
- CaltechAUTHORS:20170216-115033422
- R01DE023193
- NIH
- F31DE024931
- NIH Predoctoral Fellowship
- Burroughs Wellcome Fund
- Created
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2017-02-16Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field