Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Host-Microbe Interactions

Background:

• Iron is crucial for bacterial growth but is sequestered by the host as an immune defense.
• Most studies on bacterial iron acquisition occur in vitro, not reflecting complex host environments.
• The Fur protein is a key regulator of bacterial iron homeostasis.

Purpose of the Study:

• To characterize the iron-restricted and Fur regulons in Aggregatibacter actinomycetemcomitans.
• To investigate how the microbiome influences bacterial iron acquisition strategies.
• To assess iron availability for A. actinomycetemcomitans in different infection sites.

Main Methods:

• RNA-sequencing (RNA-seq) to analyze gene expression under iron restriction.
• Chromatin immunoprecipitation sequencing (ChIP-seq) to identify Fur-binding sites.
• Infection models including murine abscesses and human gum infections.

Main Results:

• Iron restriction and Fur regulate approximately 4% and 3.5% of the A. actinomycetemcomitans genome, respectively.
• Fur directly regulates Dispersin B, an enzyme involved in biofilm dispersal, enabling escape from iron-scarce conditions.
• A. actinomycetemcomitans experiences iron restriction in human gum infections and during co-infection with Streptococcus gordonii, but not in murine abscesses.

Conclusions:

• Bacterial iron homeostasis is tightly controlled by regulators like Fur, influencing virulence factors such as biofilm dispersal.
• Host iron availability is dynamic and context-dependent, influenced by the presence of other microbes.
• Understanding bacterial iron acquisition in vivo is critical for developing effective anti-microbial strategies.