Antimicrobial activity of polymyxin A, and characterisation of the cognate biosynthetic gene cluster within the genome of the producing Paenibacillus polymyxa.

We report the isolation and identification of a Paenibacillus polymyxa strain from the citizen science project; Swab and Send. Through whole genome sequencing we are able to describe the biosynthetic gene cluster of polymyxin A produced by P. polymyxa 1G (NCBI accession no. JBVPZV000000000), compare the pmxA, pmxB and pmxE genes to five other polymyxin genes encoding known polymyxin variants, and provide mass spectrometry data that supports the production of polymyxin A1 (1157 m/z) and A2 (1143 m/z). Polymyxins are ranked in the highest priority critically important antimicrobials classification by the WHO and are of particular importance for treating gram-negative multidrug resistant pathogens. Due to the discovery of polymyxins occurring in the 1940s, there is little genetic research around polymyxins, and the literature focusses primarily on clinically used polymyxin E (colistin) and polymyxin B. Previous literature suggests that polymyxin A1 has similar/lower toxicity to clinically used polymyxins E and B. To test if polymyxin A was able to overcome current resistance mechanisms to clinically used polymyxins, the cell free supernatant from P. polymyxa 1G was tested against a panel of clinical isolates with various resistance genes. We found that resistance genes mcr-1 and mcr-4 confer resistance to polymyxin A produced by our isolate meaning that, while polymyxin A has good antimicrobial activity, clinical resistance mechanisms already confer resistance to this variant of polymyxin.