Biomedical engineer James Collins on bacterial persisters, mammalian metabolism, and antibiotics
What are the problems surrounding treatment of bacterial persisters? Which agents can increase an antibiotics efficacy against persisting infections? Boston University Professor of Biomedical Engineering, James Collins, describes new ways to cure repeating infections.
What they did was apply a number of different sugars and metabolites to bacterial cultures, and what they found was fascinating. One was that during the time window of interest, the first 4-8 hours, these different sugars and metabolites did not wake up the cells. Yes, if you look at 24 hours, 48 hours you had some, a few number wake up, but during the window we want to test they didn’t wake up. Two was that two different classes of antibiotics we looked at – quinolones and β-lactams – were unable to kill off any of the bacteria as a result of the applied metabolite.
What we found was that by including mannitol we could substantially boost the killing efficacy of gentamicin against the biofilm. We could eradicate the biofilm infection in mice. Most stunningly, we reduced the spread of the infection to the bladder and kidneys of the mouse. So we’re very excited about how this might be useful now to go after chronic urinary tract infections, how this might be used to go after ear infections, lung-based infections, staph infections. We have early data to indicate that it can be applied to pseudomonas inside the lung. Now we just did it in vitro, but it’s often a lung-based infection that, for example, is highly problematic for cystic fibrosis patients.
Looking further, I think, the field will develop pretty dramatically in the next 5-10 years, as we learn more about the biology and physiology of persisters. They’ve been incredibly hard to study, because they make up a tiny fraction of a living population. So to actually pull them out and study them using high-throughput means (to look at the gene expression and metabolites, the protein) has been incredibly challenging. So many insights are waiting to be discovered, and I think, as we learn more about their physiology we will be that much more effective at preventing their formation and/or eradicating them once they form.