title: Proteome changes associated with Leishmania donovani promastigote adaptation to oxidative and nitrosative stresses.
abstract: Phagocytic cells produce reactive oxygen and nitrogen species (ROS & RNS) as the most common arsenal to kill intracellular pathogens. Leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. Adaptation of Leishmania to the toxic effects of ROS and RNS, involves a rapid change in the parasite proteome to combat the host defense response that macrophage mount in combating pathogen. To understand the events associated with combating ROS and RNS species, we performed a proteomic analysis of L. donovani promastigotes treated with sub-lethal doses of menadione (ROS), S-nitroso-N-acetylpenicillamine (RNS) or combination of both compounds. Proteomic changes triggered by these reagents were evaluated by iTRAQ labeling and subsequent LC-MALDI-TOF/TOF-MS analysis. Across the 3 stress conditions, the quantitative analysis identified changes in the proteins which encompass ~20% of the parasite proteome. Major changes were observed in enzymatic machinery of pathways involved in maintaining redox homeostasis, trypanothione metabolism, oxidative phosphorylation, superoxide metabolism, mitochondrial respiration process and other essential metabolic pathways. These observations shed light on how Leishmania promastigotes counter ROS and RNS effects during the initial stage of infection. This article is part of a Special Issue entitled: From protein structures to clinical applications.
authors: Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna-800007, Bihar, India.
authors: Abul Hasan
authors: AH
authors: Sardar
authors: Sudeep
authors: S
authors: Kumar
authors: Ashish
authors: A
authors: Kumar
authors: Bidyut
authors: B
authors: Purkait
authors: Sushmita
authors: S
authors: Das
authors: Abhik
authors: A
authors: Sen
authors: Manish
authors: M
authors: Kumar
authors: Kislay Kumar
authors: KK
authors: Sinha
authors: Dharmendra
authors: D
authors: Singh
authors: Asif
authors: A
authors: Equbal
authors: Vahab
authors: V
authors: Ali
authors: Pradeep
authors: P
authors: Das
mesh_terms: D000222:Adaptation, Physiological; D006801:Humans; D007893:Leishmania donovani / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D024483:Vitamin K 3 / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology
chemical_list: D020543:Proteome; D015800:Protozoan Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014815:Vitamins; D024483:Vitamin K 3