{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:06Z","timestamp":1792037106052,"version":"4.4.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Amphotericin B (AmB), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in India. AmB relapse cases and the emergence of secondary resistance have now been reported. To understand the mechanism of AmB, differentially expressed genes in AmB resistance strains were identified by a DNA microarray and real-time reverse transcriptase PCR (RT-PCR) approach. Of the many genes functionally overexpressed in the presence of AmB, the ascorbate peroxidase gene from a resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            strain (LdAPx gene) was selected because the gene is present only in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>\n            , not in humans. Apoptosis-like cell death after exposure to AmB was investigated in a wild-type (WT) strain in which the LdAPx gene was overexpressed and in AmB-sensitive and -resistant strains. A higher percentage of apoptosis-like cell death after AmB treatment was noticed in the sensitive strain than in both the resistant isolate and the strain sensitive to LdAPx overexpression. This event is preceded by AmB-induced formation of reactive oxygen species and elevation of the cytosolic calcium level. Enhanced cytosolic calcium was found to be responsible for depolarization of the mitochondrial membrane potential and the release of cytochrome\n            <jats:italic>c<\/jats:italic>\n            (Cyt\n            <jats:italic>c<\/jats:italic>\n            ) into the cytosol. The redox behavior of Cyt\n            <jats:italic>c<\/jats:italic>\n            showed that it has a role in the regulation of apoptosis-like cell death by activating metacaspase- and caspase-like proteins and causing concomitant nuclear alterations, as determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and DNA fragmentation in the resistant strain. The present study suggests that constitutive overexpression of LdAPx in the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n            AmB-resistant strain prevents cells from the deleterious effect of oxidative stress, i.e., mitochondrial dysfunction and cellular death induced by AmB.\n          <\/jats:p>","DOI":"10.1128\/aac.02834-14","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T06:36:28Z","timestamp":1407825388000},"page":"6172-6184","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Ascorbate Peroxidase, a Key Molecule Regulating Amphotericin B Resistance in Clinical Isolates of Leishmania donovani"],"prefix":"10.1128","volume":"58","author":[{"given":"Ashish","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidyut","family":"Purkait","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul Hasan","family":"Sardar","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayan Kumar","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manas Ranjan","family":"Dikhit","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Abhishek","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Life in the 21st century. 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