Humans are currently locked in an arms race against pathogenic bacteria – and we're losing. After we developed antibiotics, starting with penicillin in the early 20th century, bacteria have evolved resistance to each new drug we created, threatening us with a future where antibiotics simply don't work anymore. Now scientists have identified the genes responsible for antibiotic resistance in a particularly dangerous superbug, and found a way to thwart them.
Methicillin-resistant Staphylococcus aureus (MRSA) is a persistent strain of the Staph bacteria that, as its name suggests, is immune to methicillin, an advanced antibiotic originally designed to one-up bugs that had become resistant to penicillin. Most dangerous to people with weakened immune systems, MRSA often spreads through hospitals and retirement homes and is increasingly difficult to treat.
In previous work, a Cambridge team discovered that MRSA could become susceptible to penicillin again – but only if the antibiotic was paired up with another drug, called clavulanic acid. This latter drug is known to inhibit beta-lactamase, the enzyme the bacteria use to destroy penicillin.
For the new study, researchers from the UK, US, Denmark, Germany and Portugal set out to find the genetic root of this ability in the bacteria. They managed to spot several mutations in genes related to a protein called penicillin-binding protein 2a (PBP2a). As you might expect, this is the protein that allows MRSA to keep growing in the presence of penicillin.
Two of the mutations that the team found reduced the expression of PBP2a, while two others helped penicillin bind to the protein when clavulanic acid is around. Taken together, these mutations explain how this particular drug pair can kill some strains of MRSA. Importantly, it works on some of the most common types of the bug, including the USA300 clone.
Next up, the team tested the combo on moth larvae and mice, and sure enough, it staved off MRSA infection.
"This study highlights the importance of genomic surveillance – collecting and sequencing representative collections of bacterial strains," says Ewan Harrison, first author of the study. "By combining the DNA sequencing data generated by genomic surveillance with laboratory testing of the strains against a broad selection of antibiotics, we may find other unexpected chinks in the armor of antibiotic-resistant bacteria that might give us new treatment options."
Penicillin and clavulanic acid aren't the first drugs to team up to take down superbugs. To buy us some time while new antibiotics are developed, researchers have found success by making dynamic duos out of two existing antibiotics, two failed ones, probiotics and antibiotics, and even blue light and mild antiseptics.
The researchers say that more experimental work needs to be done before human clinical trials can begin, but the discovery is an exciting first step.
The research was published in the journal Nature Microbiology.
Source: University of Cambridge
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