It’s great to be able to report some much-need progress on the drug discovery front, with a Nature paper about a new antibacterial, lugdunin. Lugdunin is produced by S. lugdunensis and probably explains why this organism can out-compete S. aureus to colonise the nasal passages. Whilst the research has generated a great deal of positive press coverage – and so it should – but much like teixobactin, it will not go far to alleviate our problems with anti-infective-resistant bacteria.
First, and probably most importantly, lugdunin only has activity against Gram-positive bacteria. Whilst we can always use more options for treating anti-infective-resistant Gram-positives, we already have quite a few options for these bacteria. It’s the resistant Gram-negative bacteria that are causing us to run out of options. We have already seen reports of pan-drug resistant Gram-negative bacterial infections – and lugdunin won’t help with these.
Second, lugdunin is a long way from the hospital anti-infective formulary. The initial animal studies look promising, but many-a-drug has looked promising in animal models and failed when it comes to human trails. Lugdunin has a long road ahead of it before it is used to treat human infections in earnest.
Third, again much like teixobactin, the authors include some data suggesting that S. aureus does not instantly become resistant to lugdunin. This is all well and good, but it would be naïve in the extreme to think that lugdunin is any less prone to the development of reduced susceptibility and resistance than any other antibiotic. Give S. aureus a little time (and ideally a bit of sub-lethal exposure and cheap, incorrectly formulated lugdunin), and I have no doubt that resistance will emerge.
So, it’s good to see some progress towards a new anti-infective agent, but we need to train our drug discovery target on resistant Gram-negative bacteria.
One thought on “Lugdunin: a storm in a nasal passage?”
The key phrase for me in this posting is “out-compete”. Utilization of the principle of “Competitive Exclusion” as a means of addressing the presence of pathogens has been greatly over looked, especially in the area of cleaning the surfaces which nurture pathogens that become a risk via transfer to people.
Probiotic cleaning products use deploy safe, healthy probiotic bacteria into an environment such that they out-consume the available food resource and so the pathogens starve to death; a process that offers zero risk of mutation as no living entity has been able to mutate to survive starvation.
The effectiveness of probiotics deployed in this way has been shown in research to be an effective antimicrobial, and address the issues of pathogen attachment to surfaces, and the formation of biofilm which protects pathogens once they have attached: (such as this paper from Walter Reed Army Institute of Research -http://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-14-197 )
As I have stated in comments to previous postings in this forum, the addition of a biological component to cleaning products / protocols to address the biological problem of pathogen bacteria (and the biofilms they form) is a natural and logical conclusion, especially given the increasing evidence of the failure of conventional chemistry only based solutions.
This article in Nature detailing how Lugdunin (via S.lugdunensis) can impact a pathogen S.aureus through Competitive Exclusion is just another validation of this approach. If this instance is worthy of such attention (and dare I say excitement) then the healthcare and cleaning industries world wide should be equally excited at the successful implementation of this same approach in pro-active, preventative cleaning products that use safe, healthy probiotics to address the risks of pathogen bacteria.