Date Published: 7 April 2011

Marine bacteria can attach 2 antibiotics to form chemical to kill drug-resistant strains of MRSA

Recent research has lead to advances in how to kill drug-resistant strains of the MRSA so-called "superbug".
This follows from studies by scientists at Bristol and Birmingham Universities (England, UK) in collaboration with Japanese pharmaceutical company Daiichi-Sankyo. Together they have discovered how marine bacteria join together two antibiotics they make independently to produce a potent chemical that can kill drug-resistant strains of the MRSA superbug. This scientific discovery may lead to the creation of new hybrid antibiotics that may help to solve the growing problem of bacterial infections that are resistant to essentially all antibiotics.

The research team determined the sequence of the complete DNA content of the marine bacterium that produces the new antibiotic, thiomarinol - which is owned by Daiichi-Sankyo. They also identified the genes responsible for making the antibiotic on the basis of their similarity to genes that make the related but less potent antibiotic, mupirocin, which is currently used to combat MRSA (methicillin resistant staphylococcus aureus).

They found that the genes are on a relatively small, separate DNA molecule called a plasmid, which is just big enough to carry the genes for making the antibiotic plus genes to allow the plasmid to replicate autonomously in the bacterium. The plasmid thus carries genes that make both the mupirocin-like antibiotic as well a second antibiotic, holomycin, and a gene responsible for joining both antibiotics together, forming a more potent molecule.

Tests showed that by joining the antibiotics together the resulting chemical is able to inhibit the growth of MRSA strains that have become resistant to mupirocin.

Professor Chris Thomas, lead researcher from the University of Birmingham, said:

" This shows how mupirocin can be modified to make it more potent and suggests that related molecules could be used against the increasingly problematic Enterobacteriacae like Escherichia coli and Klebsiella pneumoniae."

By using mutant strains that were unable to make either the mupirocin part or the holomycin part the team was able to feed alternative compounds to the bacteria ? so-called mutasynthesis - so that a family of novel molecules was created, and tests showed some of these had biological activity.

Professor Tom Simpson from the University of Bristol's School of Chemistry, added:

" This provides hope that the system will allow the production of new antibiotics that may help to combat the growing problem of antibiotic resistance in pathogenic bacteria."

Reference to Paper:
"A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic" by Daisuke Fukuda and Anthony S. Haines et.al. is published online in the journal PLoS ONE where it is available for open-access at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018031 (copy and paste this link into your browser).

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