Sivasankar Seshan, Boppe Appalaraju, Grobusch Martin Peter, Jeyaraj Sankarganesh
PSG Center for Molecular Medicine and Therapeutics, PSG Institute of Medical Sciences and Research, Coimbatore, India.
PSG Center for Genetics and Molecular Biology, Off Avinashi Road, Coimbatore, India.
New Microbes New Infect. 2024 Jun 20;60-61:101444. doi: 10.1016/j.nmni.2024.101444. eCollection 2024 Aug-Oct.
Multidrug resistant bacterial and fungal pathogens are resistant to a number of significant front-line drugs, hence, identification of new inhibitory agents to combat them is crucial. In this study, we aim to evaluate the activity of Pandemic Box compounds from Malaria Medicines Venture (MMV) against and bacterial, fungal clinical isolates.
Isolates were initially screened with 201 antibacterial and 46 antifungal compounds (10 μM) using a microbroth dilution in triplicates to determine MIC. A persister assay was performed for bacterial pathogens.
Out of 201 antibacterial compounds, twenty-nine and seven compounds inhibited the growth of and at 10 μM, respectively. MMV1580854, MMV1579788, eravacycline and epetraborole inhibited both the bacterial test isolates. In a persister assay, MMV1634390 showed complete bactericidal effect against . With antifungal activity compounds, responded to15 compounds, Six compounds inhibited and one was effective against at 10 μM. The ratio of Minimum Fungicidal Concentration (MFC): Minimum Inhibitory Concentration (MIC) of MMV1782110 was 2 against . . Eberconazole, amorolfine and luliconazole are fungicidal targeting at a MFC: MIC ratio of 2.
Five compounds from MMV Pandemic Box were found to be inhibiting colistin and ceftazidime resistant clinical isolate, also against colistin and β-lactam resistant clinical isolate MMV1634390 showed complete bactericidal effect against in a persister assay. MMV1782110, Eberconazole, amorolfine and luliconazole exhibited potent anti-fungal activity. Further investigations are warranted to identify the targets and mechanism.
多重耐药细菌和真菌病原体对多种重要的一线药物具有抗性，因此，鉴定新的抑制剂来对抗它们至关重要。在本研究中，我们旨在评估疟疾药物风险投资公司（MMV）的大流行药物盒化合物对细菌和真菌临床分离株的活性。
最初使用微量肉汤稀释法一式三份，用201种抗菌化合物和46种抗真菌化合物（10μM）对分离株进行筛选，以确定最低抑菌浓度（MIC）。对细菌病原体进行了持留菌检测。
在201种抗菌化合物中，分别有29种和7种化合物在10μM时抑制了[具体细菌名称1]和[具体细菌名称2]的生长。MMV1580854、MMV1579788、依拉环素和依帕硼烷抑制了两种细菌测试分离株。在持留菌检测中，MMV1634390对[具体细菌名称3]显示出完全杀菌作用。对于具有抗真菌活性的化合物，[具体真菌名称1]对15种化合物有反应，6种化合物在10μM时抑制了[具体真菌名称2]，1种对[具体真菌名称3]有效。MMV1782110对[具体真菌名称4]的最低杀菌浓度（MFC）与最低抑菌浓度（MIC）之比为2。益康唑、阿莫罗芬和卢立康唑对[具体真菌名称5]具有杀菌作用，MFC:MIC之比为2。
发现MMV大流行药物盒中的5种化合物可抑制对黏菌素和头孢他啶耐药的[具体细菌名称6]临床分离株，也可抑制对黏菌素和β-内酰胺耐药的[具体细菌名称7]临床分离株。MMV1634390在持留菌检测中对[具体细菌名称8]显示出完全杀菌作用。MMV1782110、益康唑、阿莫罗芬和卢立康唑表现出强大的抗真菌活性。有必要进一步研究以确定靶点和作用机制。
