Search for Novel Arsenic-Containing Antibiotics
Disciplines
Microbial Physiology | Microbiology
Abstract (300 words maximum)
Arsenic is one of the most potent environmental toxins. On one hand, therefore, many bacteria have evolved arsenic-detoxifying mechanisms to counteract such a powerful substance. On the other hand, surprisingly, some bacteria utilize arsenic in metabolism, as an electron acceptor/donor, osmosis, or other functions. Another way to employ arsenic is in antibiotics. Some bacteria weaponize environmental arsenic to combat other bacteria, producing compounds with potential medical uses, as represented by arsinothricin (AST), the first known arsenic-containing antibiotic that controls various pathogens. These insights open new pathways in the pharmaceutical field to innovate in novel, arsenic-containing antibiotics that can help combat modern, high-priority diseases like tuberculosis and malaria. The goal of this project is to identify novel arsenic-containing antibiotics, which we hope can be utilized long-term to shed light on our shrinking antibiotic arsenal and help combat drug-resistant bacteria. The gene set (so-called biosynthetic gene cluster, or BGC) required for AST biosynthesis was used to search bacterial genome databases, which led to the discovery of several prospective BGCs for novel arsenic-containing antibiotics. In this project, four bacterial strains with the prospective BGCs were selected and cultured with arsenic under various conditions, testing their ability to produce novel arsenic-containing antibiotics. After several days of culture, bacterial cells were removed by centrifuge, and the resulting supernatant (i.e., liquid medium) were collected, and arsenic species in the media was analyzed by liquid chromatography coupled with inductively-coupled plasma mass spectrometry (LC-ICP-MS). As expected, unknown arsenic species were detected from some of the cultures, suggesting that the prospective BGCs are for novel arsenic-containing antibiotics. We are currently repeating the experiments to confirm the obtained results. Our study will provide insight into the arsenic biogeochemical cycles of various bacterium and their potential uses in the drug industry and medical field.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Masafumi Yoshinaga
Search for Novel Arsenic-Containing Antibiotics
Arsenic is one of the most potent environmental toxins. On one hand, therefore, many bacteria have evolved arsenic-detoxifying mechanisms to counteract such a powerful substance. On the other hand, surprisingly, some bacteria utilize arsenic in metabolism, as an electron acceptor/donor, osmosis, or other functions. Another way to employ arsenic is in antibiotics. Some bacteria weaponize environmental arsenic to combat other bacteria, producing compounds with potential medical uses, as represented by arsinothricin (AST), the first known arsenic-containing antibiotic that controls various pathogens. These insights open new pathways in the pharmaceutical field to innovate in novel, arsenic-containing antibiotics that can help combat modern, high-priority diseases like tuberculosis and malaria. The goal of this project is to identify novel arsenic-containing antibiotics, which we hope can be utilized long-term to shed light on our shrinking antibiotic arsenal and help combat drug-resistant bacteria. The gene set (so-called biosynthetic gene cluster, or BGC) required for AST biosynthesis was used to search bacterial genome databases, which led to the discovery of several prospective BGCs for novel arsenic-containing antibiotics. In this project, four bacterial strains with the prospective BGCs were selected and cultured with arsenic under various conditions, testing their ability to produce novel arsenic-containing antibiotics. After several days of culture, bacterial cells were removed by centrifuge, and the resulting supernatant (i.e., liquid medium) were collected, and arsenic species in the media was analyzed by liquid chromatography coupled with inductively-coupled plasma mass spectrometry (LC-ICP-MS). As expected, unknown arsenic species were detected from some of the cultures, suggesting that the prospective BGCs are for novel arsenic-containing antibiotics. We are currently repeating the experiments to confirm the obtained results. Our study will provide insight into the arsenic biogeochemical cycles of various bacterium and their potential uses in the drug industry and medical field.