Researchers from Imperial College London, CABI and the University of Oxford, have sequenced the genome of Fleming’s original Penicillium strain using samples that were frozen over fifty years ago.
The clinical use of antibiotics has revolutionised the treatment of bacterial infections. In 1928, Fleming began conducting a series of experiments involving the common staphylococcal bacteria. After he left an uncovered petri dish next to an open window, Fleming returned to find that mould spores had contaminated the dish. However, Fleming observed that bacteria within proximity to the mould colonies were dying. After isolating the mould, Fleming identified a member of the Penicillium genus – now classified as Penicillium rubens.
This sparked a golden age in antibiotic development and their use in combatting bacterial disease. However, it soon became apparent that these effects were short-lived, with pathogenic bacteria evolving resistance to these compounds. Consequently, there is an ongoing arms race between clinical use of antibiotics and the evolution of resistance in target bacteria. Researchers therefore require new classes of antibiotics and new methods to deliver them in order to gain the upper hand.
In a study, published in Scientific Reports, researchers reported the draft genome sequence of the original P. rubens isolate. The team also compared the structure of the genome and genes involved in penicillin synthesis with those in two ‘high producing’ industrial strains of P. rubens used in the US and the closely-related species P. nalgiovense. They hoped to gain an insight into the evolution of genes underlying penicillin production to help with designing new antimicrobial drugs.
The team found that the Fleming strain and both industrial strains had a suite of regulatory genes that were conserved. The industrial strains, however, had more copies of the regulatory genes, helping these strains produce more penicillin. In addition, the main effector genes for producing penicillin differed between the strains. This demonstrated that wild Penicillium evolved naturally to produce slightly different versions of these enzymes. These strains likely evolved differently to adapt to their local microbes.
The team believe that these results could help introduce potential new ways to modify penicillin production.
Ayush Pathwak, first author on the paper, stated:
“Our research could help inspire novel solutions to combatting antibiotic resistance. Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes.
But it is possible that industrial methods might have missed some solutions for optimising penicillin design, and we can learn from natural responses to the evolution of antibiotic resistance.”
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