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Monash University researchers have identified a new resistance gene in C. difficile that allows the bacterium to evade spore-blocking antibiotics, marking a significant escalation in the evolutionary battle against hospital-acquired infections.
In 1928, Alexander Fleming left a petri dish unsealed and later found it overgrown with a green fuzz that had partly killed his culture ofClostridioides difficile commonly causes severe gut infections in hospitals.
Scientists have uncovered a new way it’s evolving to outfox drugs. That was the opening salvo in what would become an evolutionary battle between medical researchers and their pathogenic microbial enemies that have rapidly evolved to outfox antibiotics and kill more than 1.2 million people each year through drug-resistant infections. But recently, an unexpected discovery by scientists at Monash University has unveiled both a new weapon against bacteria and an unexpected defence.
“Bacteria are evolving in ways that we’re not anticipating – it’s creating another level of superbug,” says Professor Dena Lyras, director of the Monash Biomedicine Discovery Institute, who focuses on a hospital-haunting bug that can unleash deadly diarrhoea.. And it’s sort of a bit hidden. But we have elderly patients who become very sick and die of it,” Lyras says.
The researchers’ lab-raised bacterium grew fine, but it couldn’t make spores, which in this species is key to reproduction and infection. The researchers were stumped.
“Gosh, they’re tough, I tell you … You irradiate them for 200 hours and they still aren’t 100 per cent dead. ”They investigated the batch and discovered the liquid medium they were growing the bacteria in contained a type of substance called a cephamycin.
“A lot of spores are made in the patient as they’re infected. We discovered a group of antibiotics that actually stopped sporulation in its tracks,” Lyras says.
“It was fantastic. ”“In about 10 per cent of the strains that we examined, this sporulation-blocking strategy didn’t work. We wondered why it wasn’t working – and that’s where we discovered this subset of strains that have this new resistance gene. ”case, gleefully infect people’s colons – and a “spore” form.
These spores are extremely hard to kill.
“Spores are the survival version of the cell,” Lyras says. “They’ve got their DNA packed in the middle, and then they’ve got layers of stuff around them like an armoured truck, tightly packed without that much water. So it’s just really tough. ”is an antibiotic resistance gene arising in the spore form of bacteria – not the normal form – for the first time.
“We hadn’t anticipated that; it’s not been described before, and it’s making that cell type tougher, stronger, more likely to survive in the environment. That’s going to have repercussions in a hospital where you can’t kill these spores off,” Lyras says.
“Gosh, they’re tough, I tell you. You’ve got to have like half an hour of contact with bleach to kill them. You irradiate them for 200 hours and they still aren’t 100 per cent dead. ” In the resistant bacteria, a new gene codes for a protein that can continue making spores, even when hit by antibiotics.
Because they’re already Terminator-tough, spores taking on a drug-resistant gene create the “ultimate superbug”, like a seed that can lie dormant in soil for years before sprouting, Lyras says. Off the back of the findings, Lyras asks: “Do we need to rethink our strategies that we’re using to clean the hospitals, to clean the beds, to clean the surfaces, to clean the sheets, to clean the toilets and the sinks?
”Deaths from infections that were previously treatable with antibiotics will exceed 10 millionA decline in global GDP of between 3.8-5%estimated the installation of copper-infused resin on counter tops, sinks, tray tables and bedside rails in a Texan hospital had prevented 78Some scientists, including microbiologist Dr Kenya Fernandes, have turned to natural solutions like honey to address the critical global health crisis of antimicrobial resistance. Another promising approach is engineering viruses called bacteriophages to attack and kill superbugs.
The problem is that much of the blue-sky research that uncovers new antibiotic molecules is underfunded. Converting one of these compounds into a useful drug is then enormously expensive and time-intensive. There’s also little incentive for big pharmaceutical companies to bring new antibiotics to market. Antibiotics might be used just once and even then, the mantra is to not overuse them lest you contribute to the antibiotic resistance problem.
New drugs are also often quickly out-evolved. Experts have urged the government to set up a “Netflix” style agreement that would see regulator payments pour into pharmaceutical companies, like a subscription, in return for access to a stream of new antibiotics. In four years, goes one estimate, 10 out of Victoria’s 14 independent research institutes will have to close.
Much of the pioneering work to tackle the thorny issue of antimicrobial resistance occurs at these kinds of agile, independent research centres.
C. Difficile Antibiotic Resistance Monash University Superbug Spore Formation
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