Abstract:
:Protozoan parasites of the Leishmania donovani complex are the causative agents of visceral leishmaniasis (VL), the most severe form of leishmaniasis, with high rates of mortality if left untreated. Leishmania parasites are transmitted to humans through the bite of infected female sandflies (Diptera: Phlebotominae), and approximately 500,000 new cases of VL are reported each year. In the absence of a safe human vaccine, chemotherapy, along with vector control, is the sole tool with which to fight the disease. Miltefosine (hexadecylphosphatidylcholine [HePC]), an antitumoral drug, is the only successful oral treatment for VL. In the current study, we describe the phenotypic traits of L. donovani clonal lines that have acquired resistance to HePC. We performed whole-genome and RNA sequencing of these resistant lines to provide an inclusive overview of the multifactorial acquisition of experimental HePC resistance, circumventing the challenge of identifying changes in membrane-bound proteins faced by proteomics. This analysis was complemented by assessment of the in vitro infectivity of HePC-resistant parasites. Our work underscores the importance of complementary "omics" to acquire the most comprehensive insight for multifaceted processes, such as HePC resistance.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Vacchina P,Norris-Mullins B,Abengózar MA,Viamontes CG,Sarro J,Stephens MT,Pfrender ME,Rivas L,Morales MAdoi
10.1128/AAC.00478-16subject
Has Abstractpub_date
2016-06-20 00:00:00pages
4089-100issue
7eissn
0066-4804issn
1098-6596pii
AAC.00478-16journal_volume
60pub_type
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