People with cystic fibrosis, diabetes, and chronic obstructive pulmonary disease often develop serious and even life-threatening bacterial infections that are hard to treat, in large part because the bacteria form dense clusters called biofilms. Biofilms are resistant to the host's immune cells and to antibiotics.
Now, new research shows that over time, some of these bacteria can evolve the ability to strengthen their biofilms, making it even harder for the host's immune cells to break them up and consume the bacteria. The bacteria Pseudomonas aeruginosa do this trick by secreting more and more of a carbohydrate that links up with proteins to form a tough, super glue-like network between bacteria.
Vernita Gordon and her colleagues, who publish the findings this week in the journal npj Biofilms and Microbiomes, are now investigating whether blocking the carbohydrate from binding to a specific protein would prevent the resulting biofilm from becoming tougher. If so, it would be a good target for future therapies, making the biofilm more vulnerable to the host's own immune system.
"And that would be awesome because the standard antibiotic for these infections is tobramycin, which is nasty," says Gordon, assistant professor of physics. "It causes kidney damage and deafness. The secondary and tertiary antibiotics are even more awful. So if you can reduce antibiotic treatment that's needed because you've made the patient's immune system more effective, that would be a big benefit."
Gordon says preventing bacteria from strengthening their biofilms by attacking the carbohydrates they produce would still work even if the bacteria become antibiotic resistant.
"And that's important given how fast antibiotic resistance is increasing," she says. "We need new ways to approach these diseases that are in an antibiotics arms race with us, because it's pretty clear, the bacteria are going to win that race."
In cystic fibrosis (CF), a serious genetic disease that afflicts roughly 30,000 Americans, patients produce thick, dry mucus in their lungs that is hard to cough up and, unfortunately, provides an ideal breeding ground for bacterial infections. Pseudomonas, the same bacteria that is so dangerous in CF patients, also causes intractable infections in chronic wounds in the lower limbs of diabetics. This is the most common cause of amputation for diabetic patients. According to the Centers for Disease Control and Prevention, 29 million Americans have diabetes and, per year, about 70,000 have part of a lower limb amputated.
"This new perspective has the potential to improve the lives of a lot of people," says Gordon.
The paper is the sixth in the past year published by the Gordon lab examining physical aspects of biofilms.
The research was funded by the University of Texas at Austin, ExxonMobil and grants from the Human Frontiers Science Program and the National Science Foundation.