Discussion
By 2050, antimicrobial resistance (AMR) will cause mortality to more people than cancer. Resistant Gram negative bacteria present a serious challenge due to limited or no treatment options for infections using current antibiotics. There is therefore an urgent need to develop better understanding on how to target drug-resistant Gram negative bacteria.
To address the challenges from Gram negative bacteria, we have shown for the very first time that Moenomycin A (MoeA) can be effective against the resistant Gram negative bacteria. MoeA is largely inactive and unexploited against Gram negative bacteria. MoeA is the most potent naturally occurring inhibitor of a family of glycosyltransferases (GT51), highly conserved enzymes in resistant bacteria central to producing peptidoglycan. Targeting GT51 enzyme activity by MoeA is an excellent antimicrobial strategy because (1) GT51 is essential for bacterial survival and (2) no significant natural cross resistance has been reported for MoeA, despite its use for decades in animal feed.
We have pioneered a unique approach to target resistant Gram negative bacteria using MoeA and have showed a substantial reduction in MIC in resistant Gram negative bacteria: 16 times for P. aeruginosa,8 times for K. pneumoniae and 8 times for A. baumannii. The latest results on targeting Gram negatives using MoeA will be presented.