Some antibiotic news today: first off, there’s a new multinational collaboration (CARB-X) to work on drug-resistant bacteria. Among other things, it’ll be giving grants to small companies in the US and Europe who are working in the area. They’re especially targeting new varieties of compounds, rather than variations on existing scaffolds, which I think is a good use of the money. It’s a public-private effort, with money coming in from the US HHS, the Wellcome Trust, and several other sources. This seems like a good idea, and it’s certainly addressing a real need, so I hope that something comes from it.
And in the odd antibiotic field, there’s this report in Nature. It’s been known for many decades that soil bacteria, since they’re in constant competition with each other, produce a variety of interesting antibiotics (in fact, many of the interesting antibiotics we have come from just that source). This hasn’t been observed much in the bacterial colonies that are present in all human bodies, but this latest paper has an example: lugdunin, a cyclic peptide thiazolidine derivative. It’s produced by Staphylococcus lugdunensis, and it’s one of the very few examples of such nonribosomally synthesized peptide natural products in human-associated bacteria.
It’s a pretty effective compound against S. aureus and a number of other gram-positive pathogens, including ones with resistance to common antibiotics. That goes for in vitro assays and in vivo ones (topical skin infection in mice). It’s clean against various human cell lines, though. Interestingly, serial passaging against the bacteria, which is a quick way to breed resistant strains, did not produce any against lugdunin. Its mode of action is unknown, although (like daptomycin) it seems to shut down a number of metabolic pathways at once. No one’s completely sure how daptomycin works, either – in general, it seems to be membrane disruption, but with specific details unknown. Lugdunin might be doing something similar, but that’s a topic for further research, which I think we can assume is underway or will be shortly.
The paper notes that a fair percentage (roughly a third) of adults have their nasal passages colonized by S. aureus, and that this correlates with the likelihood of nasal infection. There have been proposals to wipe out the pathogen from individual patients to save on trouble later on, but that isn’t easy. When this research team looked at 187 patients, they found a strong correlation between S. lugdunensis colonization (which was present in about 10% of the sample) and low incidence of S. aureus, which suggests that more people could possibly benefit by exposure to the former bacterium. In keeping with the lack of success at breeding resistant organisms, all of the clinically isolated S. aureus samples were still susceptible to lugdunin. So there are two public-health implications to this work: a potential new antibiotic, and a potential new microbiome tactic.