Euteneuer Clare F, Davis Brianna N, Lui LeeAnna M, Neville Andrew J, Davis Paul H
Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA.
Pathogens. 2025 Mar 16;14(3):290. doi: 10.3390/pathogens14030290.
The rise of bacterial infections is a global health issue that calls for the development and availability of additional antimicrobial agents. Known for its in vitro effects on Gram-positive organisms, the drug-like small molecule marinopyrrole A was re-examined for the potential of broader efficacy against a wider array of microbes. We uncovered selective efficacy against an important subset of Gram-negative bacteria from three genera: , , and . This susceptibility is correlated with the absence of canonical LPS in these specific Gram-negative species, a phenomenon observed with other hydrophobic anti-microbial compounds. Further, when exposed to molecules which inhibit the LpxC enzyme of the LPS synthesis pathway, previously resistant LPS-producing Gram-negative bacteria showed increased susceptibility to marinopyrrole A. These results demonstrate marinopyrrole A's efficacy against a broader range of Gram-negative bacteria than previously known, including , a species identified as a priority pathogen by the WHO.
细菌感染的增加是一个全球性的健康问题，需要开发和提供更多的抗菌药物。药物样小分子海栖吡咯A以其对革兰氏阳性菌的体外作用而闻名，现对其对更广泛微生物具有更广泛疗效的潜力进行了重新研究。我们发现它对三个属的重要革兰氏阴性菌子集具有选择性疗效： 、 和 。这种易感性与这些特定革兰氏阴性菌中缺乏典型的脂多糖有关，这一现象在其他疏水性抗菌化合物中也有观察到。此外，当暴露于抑制脂多糖合成途径中LpxC酶的分子时，先前耐药的产脂多糖革兰氏阴性菌对海栖吡咯A的敏感性增加。这些结果表明，海栖吡咯A对革兰氏阴性菌的疗效比以前所知的更广泛，包括 ，这是一种被世界卫生组织确定为优先病原体的物种。
