The previously unknown thiopeptide antibiotic lactocillin can fight a range of Gram-positive vaginal pathogens and could be “a rich source of therapeutics,” says a paper in Cell.
The authors found the antibiotic in Lactobacillus gasseri, a bacterium common in the vagina. The vaginal lactocillin cluster matched messenger RNA in the human mouth, backing up the theory that the antibiotic is produced by the human microbiome, but researchers said more sensitive tests are needed for conclusive proof.
They suggested future experiments to study the antibiotic’s activity “in which a lactocillin producer is compared to an isogenic strain deficient in lactocillin production.”
Thiopeptides are a family of antibiotics made of highly modified amino acids, and a linear peptide containing dehydroalanines extending from the ring of a pyridyl group.
The recently discovered set already numbers more than 100 antibiotics, which have unusual modes of action. As well as antibacterial activity, some thiopeptides hold antiplasmodial and immunosuppressive properties, although none are yet in clinical use.
Gene clusters
Altogether, the researchers found 3,118 small molecule biosynthetic gene clusters (BGCs) in the human microbiome. These included all families of BGCs, such as complex polyketides and nonribosomal peptides.
They created a database characterising the structure and activity of the BGCs for future drug discovery efforts, “as a resource for future studies that aim to discover small-molecule-mediated interactions in the human microbiota.”
“The small-molecule products of BGCs are widely used in the clinic, and they constitute much of the chemical language of interspecies interactions,” said the paper.
“Our data highlight the fact that there exist hundreds of widely distributed BGCs of unknown function in the human microbiome, and they provide a template for future experimental efforts to discover biologically active small molecules from the microbiota […].
“These molecules represent a promising starting point for studying microbe-host interactions at the level of molecular mechanism and potentially a rich source of therapeutics.”
Antibiotics cliff
Governments and NGOs are working with industry on ways to discover more antibiotics in response the impending antimicrobial resistance crisis. As microorganisms evolve to withstand antibacterial drugs, such as antibiotics, currently treatable infections risk becoming very dangerous unless alternative treatment is found.
In July this year, the Professor of Pharmaceutical Innovation at Kings College, London, told in-Pharmatechnologist.com regulators should make the “broken” antibiotics development model more attractive to drug companies by fast-tracking submissions and extending marketing exclusivity.
President Obama’s 2014 budget set aside $30m per year until 2019 for R&D into detecting and preventing “superbug” infections, while UK Prime Minister David Cameron commissioned an economic review into antibiotic resistance this summer.