Please see the preprint for details, including in vitro fitness assays. A ton of great work led by Aditi Mukherjee, together with @dhelekal.bsky.social, Sofia Blomqvist, Apabrita Das, and Samantha Palace.

Of course, we'll have to see what happens once the antibiotics start being used. But this tempers the hope that the two new antibiotics would provide a big buffer before we again face the specter of highly resistant gonorrhea.

This cross-resistance has clinical and public health implications, especially as the ParC D86N mutation seems common in Asia, where ceftriaxone resistance is highest and thus where we expect zoliflodacin to be used most heavily at first.

Turns out GyrA 92 and GyrB 429 are adjacent in the GyrA-GyrB heterodimer, suggesting that both mutations alter gepotidacin binding.

But we found that, in some strains, the zoli resistance-conferring GyrB D429N mutation can also confer resistance to gepotidacin. These strains also have the ParC D86N mutation that is known to be a stepping-stone mutation for the GyrA A92T that confers gepotidacin resistance.

Each new antibiotic is first-in-class and, like fluoroquinolones, target topoisomerases. Resistance mutations for each have been described: GyrB D429N for zoli and GyrA A92T in the background of ParC D86N for gepo. Resistance was thought to be independent.

Congratulations! Wonderful news!

Or folks from the micro lab? Maybe @sanjatkanjilal.bsky.social?

Not sure! Perhaps pulm / critical care folks could weigh in?

…is totally missing the point of publishing scientific articles. Science is always a work in progress, never a finished story. We share our observations so that others can test & build on them, to advance collective understanding. AI may not be able to comprehend this but journals and reviewers MUST

I think they’re all worth considering, and of course it’s likely multifactorial and even changing as new interventions are introduced—hence this piece! Shifting behaviors? Bexsero? Doxy-PEP?

People have their favorite explanations, but it's not clear--and without a better understanding of what's driving these trends, we won't be able to optimally inform public health interventions. We lay out the possibilities and how to address them for gonorrhea. (2/2) dash.harvard.edu/entities/pub...