It's Thursday, and the folks who cleared out of the New Orleans convention center early missed out on a great set of talks in the MEDI division about targeting fatty acid biosynthesis for antibacterial, anticancer, and other pharmaceutical applications.
The speakers working on keeping microbes at bay all brought the point home that we need new types of antibiotics (new structures and new mechanisms of action) to stave off resistance in infections like TB and staph. While not trying to trivialize the severity of infectious diseases (TB has been with us since the beginning of recorded history and is still the cause of a big chunk of the deaths in the developing world), I'll share a graphic that stuck out for me: it's a figure from the New England Journal of Medicine that speaker Judd Berman threw up.
It shows how an infection of methicillin-resistant staph spread between pro football players on the St. Louis Rams and to members of an opposing team over time and maps out the infected players' positions on field. It sounds like something on ESPN's SportsCenter that I'd need a telestrator to cover, but it's frightening to think that drug-resistant infections are spreading outside of hospitals nowadays, from something as simple as a burn from astroturf.
Back to the symposium. Blocking or reducing fatty acid biosynthesis to kill bacteria like staph isn't the newest idea (those bad bugs have cell walls that people would like to target), but the pathways are complex, and there are lots of enzymes that researchers could think about targeting or learn a little bit more about. I counted at least four appearances of the words "underexploited target" or "unexploited target" on presenters' slides.
There have also been some recent protein structure advances in this area that are giving researchers some hints and validating work that's come before.
What struck me (and was mentioned by the organizer at the end of the talk) is the sheer chemical diversity of the molecules that researchers are using to block fatty acid synthesis. They are targeting different enzymes to be sure (human versus bacterial, as well as enzymes that catalyze different steps of the biosynthesis), but there really seems to be an enormous amount of flexibility. There's a lot we don't know in this field, and hopefully more researchers (and venture capitalists) will be willing to commit the funding and take up the torch.
I'll leave you with an example of, um, macromolecular inhibitor design from Dan Romo's group at Texas A&M. He's working on beta-lactones as anticancer candidates. He tells me that taking this picture was his idea. Notice the attention to detail: He used two people side by side to form the beta-lactone carbonyl group. His students are good sports.