California Institute for Medical Research, San Jose, CA 95128, USA.
Department of Chemistry, San Jose State University, San Jose, CA 95112, USA.
Trans R Soc Trop Med Hyg. 2020 Jul 1;114(7):492-498. doi: 10.1093/trstmh/trz136.
Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease.
Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined.
Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti-T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi.
The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.
细菌是许多用于治疗传染病的分子的来源。我们研究了 26 株铜绿假单胞菌产生的分子对感染哺乳动物细胞培养的克氏锥虫（恰加斯病的病原体）的影响。
在野生型铜绿假单胞菌上清液或产毒、群体感应和铁摄取因子缺陷突变体的上清液存在的情况下，用 T. cruzi 感染 Vero 细胞。通过定量测定 T. cruzi 感染（感染细胞的百分比）和增殖（每个感染细胞的阿米巴原虫数量）以及测定细胞活力来评估 T. cruzi 感染。
野生型铜绿假单胞菌产物以剂量依赖的方式对 T. cruzi 的感染和增殖产生负面影响，而对哺乳动物细胞没有明显的毒性。PvdD/pchE 突变（丧失铜绿假单胞菌铁载体吡咯并并啉和吡咯烷酮）对抗 T. cruzi 活性的影响最大。纯吡咯烷酮而非吡咯并啉或其他研究的铜绿假单胞菌外产物对 T. cruzi 感染的负作用与当前治疗 T. cruzi 的标准疗法苯并咪唑的作用相当。
铜绿假单胞菌产物吡咯烷酮对 T. cruzi 具有有希望的活性，可能成为治疗开发的新先导分子。
