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In a new study, researchers at Indiana University Bloomington have discovered a new way that bacteria can kill its competitors in complex microbial communities, revealing novel approaches to leverage viruses to kill harmful bacteria.

The study, "Streptomyces secretes a siderophore that sensitizes competitor bacteria to phage infection," was Jan. 8, 2024 in Nature Microbiology. The first author is Zhiyu Zang, a graduate student at the IU Bloomington Department of Chemistry in the College of Arts and Sciences. The senior author is J.P. Gerdt, assistant professor of chemistry at IU Bloomington.

"It's been known for decades that bacteria compete with each other by synthesizing antibiotics and secreting them to kill their competitors, so that they can invade their competitors' space and get their nutrients," said Gerdt.

"What we found here is that bacteria secrete molecules that take away the immune system of their competitor, using viruses already around as their own advantage."

Bacteria are constantly evolving to protect themselves from bacteriophages, or viruses. When it comes to human health, understanding how bacteria can be infected is crucial, as several bacteria are essential for food and medicine production.

Researchers experimented with two bacteria: Streptomyces sp and Bacillus subtilis. These bacteria are natural competitors, and both are commonly found in soil.

They observed that in an enclosed environment with bacteriophages, Streptomyces sp weakened the immune response of Bacillus subtilis by secreting a metabolite known as coelechelin. The secretion of coelechelin, a natural product, ultimately sequestered iron away from Bacillus subtilis and impeded its ability to defend itself from the attacks of the surrounding bacteriophages.

According to Gerdt, similar collaborative killing of bacteria is likely shaping the microbiomes inside us and around us. If further explored, phage-chemical combinations like this may be helpful in treating antibiotic-resistant infections.

"This research highlights that the chemicals around bacteria really matter," said Gerdt. "We've shown that the metabolites being produced by neighboring organisms can have a huge impact on how effective the immune system is."

Additional contributors to the paper are Chengqian Zhang and Kyoung Jin Park, of the IU Bloomington Department of Chemistry, Daniel Schwartz and Jay Lennon of the IU Bloomington Department of Biology, and Ram Podicheti of the IU Bloomington Center for Genomics and Bioinformatics.