title: 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.
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX United States of America.
authors.forename: Apollo
authors.initials: A
authors.lastname: Stacy
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX United States of America.
authors.forename: Nader
authors.identifier: http://orcid.org/0000-0001-9679-5642
authors.initials: N
authors.lastname: Abraham
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX United States of America.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-0981-740X
authors.initials: P
authors.lastname: Jorth
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX United States of America.
authors.forename: Marvin
authors.initials: M
authors.lastname: Whiteley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D060085:Coinfection / Q000378:metabolism* / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016871:Pasteurellaceae Infections / Q000378:metabolism* / Q000382:microbiology; D010518:Periodontitis / Q000382:microbiology*; D025341:Principal Component Analysis; D012097:Repressor Proteins / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D054773:Streptococcus gordonii
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron