Identification of simple arylfluorosulfates as potent agents against resistant bacteria
Jiong Zhang, Xiangxiang Zhao, John R. Cappiello, Yi Yang, Yunfei Cheng, Guang Liu, Wenjing Fang, Yinzhu Luo, Yu Zhang, Jiajia Dong, Lixin Zhang, K. Barry Sharpless
Abstract
Significance Excessive use of antibiotics for patient therapy and livestock results in the selection of pathogenic bacteria resistant to multiple drugs. The spread of multidrug-resistant bacteria into the community is associated with increased morbidity, mortality, and financial burden of health care. We constructed a library of SuFEx-derived arylfluorosulfates that demonstrated potent activities in combating multidrug-resistant bacteria both in vitro and in vivo. Significantly, these arylfluorosulfate analogs show enhanced potency to disrupt bacterial biofilm as well as kill persisters and have a synergistic effect with clinical bactericidal drugs. This study suggests that arylfluorosulfates derived from SuFEx-based modification of phenols could serve as a convenient strategy to search for bactericidal candidates.