Szamosvári Dávid, Schuhmacher Tamara, Hauck Christof R, Böttcher Thomas
Department of Chemistry , Konstanz Research School Chemical Biology , Zukunftskolleg , University of Konstanz , 78457 Konstanz , Germany . Email:
Department of Biology , University of Konstanz , 78457 Konstanz , Germany . Email:
Chem Sci. 2019 May 23;10(27):6624-6628. doi: 10.1039/c9sc01090d. eCollection 2019 Jul 21.
The quinolone signal (PQS) is an important quorum sensing signal of the pathogen . We discovered an additional activity of PQS as a narrow spectrum antibiotic. Exploiting the privileged structure of PQS by the synthesis of heteroatom-substituted analogues led to a class of 2-alkyl-3-hydroxythiochromen-4-ones with highly potent antibiotic activity against the nasopharyngeal pathogen . Synthetic optimization resulted in minimum inhibitory concentrations in the nanomolar range even for clinical isolates of . Surprisingly, the growth of other human pathogens and commensals, including closely related species, was not inhibited, indicating exceptional species selectivity. Mechanistic studies revealed that the antibiotic was bactericidal and likely inhibits a target in the primary energy metabolism causing rapid depletion of the cellular ATP pool.
喹诺酮信号（PQS）是病原体的一种重要群体感应信号。我们发现PQS具有作为窄谱抗生素的额外活性。通过合成杂原子取代类似物来利用PQS的特殊结构，得到了一类对鼻咽病原体具有高效抗生素活性的2-烷基-3-羟基硫代色烯-4-酮。合成优化使得即使对于[具体病原体]的临床分离株，最低抑菌浓度也处于纳摩尔范围。令人惊讶的是，包括密切相关的[具体物种]在内的其他人类病原体和共生菌的生长并未受到抑制，这表明其具有特殊的物种选择性。机理研究表明，该抗生素具有杀菌作用，可能抑制主要能量代谢中的一个靶点，导致细胞ATP池迅速耗尽。
