A group under the direction of Stanford infectious disease investigator Paul Bollyky, MD, PhD, has uncovered a criminal conspiracy between two microbial lowlifes that explains how some of medicine’s most recalcitrant bacterial infections resist being expunged.
In a study published today in Cell Host & Microbe, Bollyky and his associates reveal that bacterial pathogens responsible for a big chunk of chronic infections can team up with a type of virus that bacteria ordinarily consider their worst enemies to form biofilms, which, our news release on the study explains, are “slimy, antiobiotic-defying aggregates of bacteria and organic substances that stick to walls and inner linings of infected organs and to chronic wounds, making infections excruciatingly hard to eradicate.” More from that release:
Biofilms factor into 75 to 80 percent of hospital-acquired infections, such as those of the urinary tract, heart valves and knee-replacement prostheses, Bollyky said. “A familiar example of a biofilm is the plaque that forms on our teeth,” he said. “You can brush twice a day, but once that plaque’s in place you’re never going to get rid of it.”
The study first focused on Pseudamonas aeruginosa, which accounts for one in ten hospital-acquired infections, many chronic pneumonia cases and much of the air-passage obstruction afflicting cystic-fibrosis patients.
Cystic fibrosis is deadly mainly because of biofilms formed by P. aeruginosa, Bollyky told me. “These biofilms fill up all the air spaces, and antibiotics can’t seem to penetrate them,” he said.
But he and his colleagues found that P. aeruginosa forms biofilms only when it’s been infected itself.
Although we larger life forms don’t give it much thought, a bacteria’s life is not without its particle of torment. There’s a little ditty that’s been attributed (almost certainly falsely) to 20th-century poet/humorist Ogden Nash, but more likely derives from a similar quatrain composed by the 18th-century satirist Jonathan Swift:
Little bugs have littler bugs
Upon their backs to bite ’em
And littler bugs have littler bugs,
And on ad infinitum.
It’s actually true. As much as we large lifeforms are dogged by teeny, single-celled bacterial pathogens, they, too, get infected – by bacteria-specific viruses called bacteriophages (“phages” for short).
Like any other virus, a phage can reproduce itself only by climbing into a cell – in this case, a bacterial cell – and, like buccaneers of yore, commandeering its replicative machinery. Usually, the pico-pirate’s plethoric progeny punish the good deed of the poor host cell that produced them by punching holes in its outer membrane and busting out of it, destroying the cell in the process.
But, the scientists demonstrated, P. aeruginosa – as well as other species of biofilm-producing bacteria – can team up with a family of phages that, instead of destroying the bacterial cells they invade, join them in constructing the bacterial equivalent of a gummy termite’s nest and rendering the bacteria extremely antibiotic-resistant.
Indeed, no phage, no biofilm.
Catching this pair of bad actors in flagrante delicto opens the gate to promising new ways of breaking up these pathogenic partnerships, thereby treating hospital-acquired infections and curing chronic disease.
Previously: Can a safe, cheap pill prevent type 1 diabetes?, Stanford med student/HHMI fellow investigates a bacteriophage theory as an alternative to antibiotics and Diverse microbes discovered in healthy lungs shed new light on cystic fibrosis
Photo by AJC ajcann.wordpress.com