Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human 2 gastrointestinal tract

A novel lanC-like sequence was identified from the dominant human gut bacterium Blautia obeum strain A2-162. This sequence was extended to reveal putative biosynthetic and transport genes, two sets of regulatory genes, immunity genes, three copies of a nisin–like lanA gene (nsoA1, 2, 3) with an unusual leader peptide and a fourth putative lanA gene (nsoA4). Comparison with other nisin clusters showed the closest relationship to nisin U.
B. obeum A2-162 demonstrated antimicrobial activity against Clostridium perfringens when grown on solid media in the presence of trypsin. Fusions of the predicted nsoA structural sequences with the nisin A leader were expressed in Lactococcus lactis containing the nisin A cluster without nisA. Expression of the nisA leader sequence fused to the predicted structural nsoA1 produced a growth defect in L. lactis which was dependent upon the presence of biosynthetic genes, but failed to produce antimicrobial activity. Insertion of the nso cluster into L. lactis MG1614 gave an increased immunity to nisin A but this was not replicated by the expression of nsoI.

Nisin A induction of L. lactis containing the nso cluster and nisRK genes allowed detection of the NsoA1 pre-peptide by Western hybridisation. When this heterologous producer was grown with nisin induction on solid media, antimicrobial activity was demonstrated in the presence of trypsin against C. perfringens, Clostridium difficile and L. lactis. This research adds to evidence that lantibiotic production may be an important trait of gut bacteria and could lead to the development of novel treatments for intestinal diseases.