Enolase Is Implicated in the Emergence of Gonococcal Tolerance to Ceftriaxone

Antibiotic tolerance is associated with antibiotic treatment failure, and molecular mechanisms underlying tolerance are poorly understood. We recently succeeded in inducing tolerance to ceftriaxone (CRO) in an N. gonorrhoeae reference isolate. In a prior in vitro study, six biological replicates of WHO P strains were exposed to CRO (10x the MIC) followed by overnight growth, and tolerance was assessed using a modified Tolerance Disc (T.D.) test. In the current study, we characterized the mutation profile of these CRO-tolerant phenotypes. The whole genome was sequenced from isolates from different replicates and time points. We identified mutations in four genes that may contribute to ceftriaxone tolerance in N. gonorrhoeae, including a mutation in the enolase (eno) gene that arose independently in three lineages.

Automated summary

Antibiotic tolerance is associated with treatment failure, but the molecular mechanisms behind it are poorly understood. In a recent study, researchers induced tolerance to ceftriaxone in N. gonorrhoeae and identified mutations in four genes that may contribute to this tolerance. These findings provide insight into the development of antibiotic tolerance in bacteria.