A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs

The extent of susceptibility towards miltefosine (Mil), amphotericin B (AmpB), and paromomycin (Paro) was measured among 19 clinical isolates of Leishmania donovani (LD). Thirteen of these clinical isolates were reported to exhibit low susceptibility towards sodium stibogluconate (SSG-R), while six...

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Autores principales:	Souradeepa Ghosh, Souvik Biswas, Sandip Mukherjee, Arijit Pal, Aaditya Saxena, Shyam Sundar, Jean-Claude Dujardin, Soumen Das, Syamal Roy, Rupkatha Mukhopadhyay, Budhaditya Mukherjee
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cross-resistance antileishmanial drug dose–response analysis non-protein thiol bioimpedance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4cd0e802605446829bac61066651e28c
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spelling	oai:doaj.org-article:4cd0e802605446829bac61066651e28c2021-12-01T13:54:12ZA Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs2235-298810.3389/fcimb.2021.768830https://doaj.org/article/4cd0e802605446829bac61066651e28c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.768830/fullhttps://doaj.org/toc/2235-2988The extent of susceptibility towards miltefosine (Mil), amphotericin B (AmpB), and paromomycin (Paro) was measured among 19 clinical isolates of Leishmania donovani (LD). Thirteen of these clinical isolates were reported to exhibit low susceptibility towards sodium stibogluconate (SSG-R), while six of them were highly susceptible (SSG-S). The degree of clearance of amastigotes (EC50) for these predefined SSG-R- and SSG-S-infected macrophages was determined against Mil, AmpB, and Paro. Two out of the 13 SSG-R isolates (BHU575 and BHU814) showed low susceptibility towards all three drugs studied, while the rest of the 11 SSG-R isolates showed varying degrees of susceptibility either towards none or only towards individual drugs. Interestingly, all the SSG-S isolates showed high susceptibility towards Mil/AmpB/Paro. The total intracellular non-protein thiol content of the LD promastigotes, which have been previously reported to be positively co-related with EC50 towards SSG, was found to be independent from the degree of susceptibility towards Mil/AmpB/Paro. Impedance spectra analysis, which quantifies membrane resistance, revealed lower impedimetric values for all those isolates exhibiting low efficacy to Mil (Mil-R). Our analysis points out that while non-protein thiol content can be an attribute of SSG-R, lower impedimetric values can be linked with lower Mil susceptibility, although neither of these parameters seems to get influenced by the degree of susceptibility towards AmpB/Paro. Finally, a correlation analysis with established biological methods suggests that impedance spectral analysis can be used for the accurate determination of lower Mil susceptibility among LD isolates, which is further validated in the LD-infected in vivo hamster model.Souradeepa GhoshSouvik BiswasSandip MukherjeeArijit PalAaditya SaxenaShyam SundarJean-Claude DujardinJean-Claude DujardinSoumen DasSyamal RoyRupkatha MukhopadhyayBudhaditya MukherjeeBudhaditya MukherjeeFrontiers Media S.A.articlecross-resistanceantileishmanial drugdose–response analysisnon-protein thiolbioimpedanceMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cross-resistance antileishmanial drug dose–response analysis non-protein thiol bioimpedance Microbiology QR1-502
spellingShingle	cross-resistance antileishmanial drug dose–response analysis non-protein thiol bioimpedance Microbiology QR1-502 Souradeepa Ghosh Souvik Biswas Sandip Mukherjee Arijit Pal Aaditya Saxena Shyam Sundar Jean-Claude Dujardin Jean-Claude Dujardin Soumen Das Syamal Roy Rupkatha Mukhopadhyay Budhaditya Mukherjee Budhaditya Mukherjee A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
description	The extent of susceptibility towards miltefosine (Mil), amphotericin B (AmpB), and paromomycin (Paro) was measured among 19 clinical isolates of Leishmania donovani (LD). Thirteen of these clinical isolates were reported to exhibit low susceptibility towards sodium stibogluconate (SSG-R), while six of them were highly susceptible (SSG-S). The degree of clearance of amastigotes (EC50) for these predefined SSG-R- and SSG-S-infected macrophages was determined against Mil, AmpB, and Paro. Two out of the 13 SSG-R isolates (BHU575 and BHU814) showed low susceptibility towards all three drugs studied, while the rest of the 11 SSG-R isolates showed varying degrees of susceptibility either towards none or only towards individual drugs. Interestingly, all the SSG-S isolates showed high susceptibility towards Mil/AmpB/Paro. The total intracellular non-protein thiol content of the LD promastigotes, which have been previously reported to be positively co-related with EC50 towards SSG, was found to be independent from the degree of susceptibility towards Mil/AmpB/Paro. Impedance spectra analysis, which quantifies membrane resistance, revealed lower impedimetric values for all those isolates exhibiting low efficacy to Mil (Mil-R). Our analysis points out that while non-protein thiol content can be an attribute of SSG-R, lower impedimetric values can be linked with lower Mil susceptibility, although neither of these parameters seems to get influenced by the degree of susceptibility towards AmpB/Paro. Finally, a correlation analysis with established biological methods suggests that impedance spectral analysis can be used for the accurate determination of lower Mil susceptibility among LD isolates, which is further validated in the LD-infected in vivo hamster model.
format	article
author	Souradeepa Ghosh Souvik Biswas Sandip Mukherjee Arijit Pal Aaditya Saxena Shyam Sundar Jean-Claude Dujardin Jean-Claude Dujardin Soumen Das Syamal Roy Rupkatha Mukhopadhyay Budhaditya Mukherjee Budhaditya Mukherjee
author_facet	Souradeepa Ghosh Souvik Biswas Sandip Mukherjee Arijit Pal Aaditya Saxena Shyam Sundar Jean-Claude Dujardin Jean-Claude Dujardin Soumen Das Syamal Roy Rupkatha Mukhopadhyay Budhaditya Mukherjee Budhaditya Mukherjee
author_sort	Souradeepa Ghosh
title	A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
title_short	A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
title_full	A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
title_fullStr	A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
title_full_unstemmed	A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
title_sort	novel bioimpedance-based detection of miltefosine susceptibility among clinical leishmania donovani isolates of the indian subcontinent exhibiting resistance to multiple drugs
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4cd0e802605446829bac61066651e28c
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A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs

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