Perspectives From Systems Biology to Improve Knowledge of Drug Resistance

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2021 May 17

PMID 33996631

Citations 4

Authors

Elvira Cynthia Alves Horacio

Jessica Hickson

Silvane Maria Fonseca Murta

Jeronimo Conceicao Ruiz

Laila Alves Nahum

Affiliations

Soon will be listed here.

Abstract

Neglected Tropical Diseases include a broad range of pathogens, hosts, and vectors, which represent evolving complex systems. Leishmaniasis, caused by different species and transmitted to humans by sandflies, are among such diseases. and other Trypanosomatidae display some peculiar features, which make them a complex system to study. Leishmaniasis chemotherapy is limited due to high toxicity of available drugs, long-term treatment protocols, and occurrence of drug resistant parasite strains. Systems biology studies the interactions and behavior of complex biological processes and may improve knowledge of drug resistance. System-level studies to understand biology have been challenging mainly because of its unusual molecular features. Networks integrating the biochemical and biological pathways involved in drug resistance have been reported in literature. Antioxidant defense enzymes have been identified as potential drug targets against leishmaniasis. These and other biomarkers might be studied from the perspective of systems biology and systems parasitology opening new frontiers for drug development and treatment of leishmaniasis and other diseases. Our main goals include: 1) Summarize current advances in research focused on chemotherapy and drug resistance. 2) Share our viewpoint on the application of systems biology to studies. 3) Provide insights and directions for future investigation.

Citing Articles

Determination of key hub genes in Leishmaniasis as potential factors in diagnosis and treatment based on a bioinformatics study.

Safaei M, Goodarzi A, Abpeikar Z, Farmani A, Kouhpayeh S, Najafipour S Sci Rep. 2024; 14(1):22537.

PMID: 39342024 PMC: 11438978. DOI: 10.1038/s41598-024-73779-w.

New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.

V Cabral F, Cerone M, Persheyev S, Lian C, Samuel I, Ribeiro M PLoS One. 2023; 18(9):e0289492.

PMID: 37713373 PMC: 10503701. DOI: 10.1371/journal.pone.0289492.

Therapeutic effect of oral quercetin in hamsters infected with .

Dos Santos R, Da Silva T, de Souza Brito A, Inacio J, Ventura B, Mendes M Front Cell Infect Microbiol. 2023; 12:1059168.

PMID: 36710981 PMC: 9880276. DOI: 10.3389/fcimb.2022.1059168.

In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase.

Kant V, Kumar P, Ranjan R, Kumar P, Mandal D, Vijayakumar S Parasitol Res. 2022; 121(7):2093-2109.

PMID: 35536513 PMC: 9085559. DOI: 10.1007/s00436-022-07532-5.

References

Maltezou H . Drug resistance in visceral leishmaniasis. J Biomed Biotechnol. 2009; 2010:617521. PMC: 2771279. DOI: 10.1155/2010/617521. View

Butcher E, Berg E, Kunkel E . Systems biology in drug discovery. Nat Biotechnol. 2004; 22(10):1253-9. DOI: 10.1038/nbt1017. View

Likic V, McConville M, Lithgow T, Bacic A . Systems biology: the next frontier for bioinformatics. Adv Bioinformatics. 2011; :268925. PMC: 3038413. DOI: 10.1155/2010/268925. View

Frezard F, Silva H, de Castro Pimenta A, Farrell N, Demicheli C . Greater binding affinity of trivalent antimony to a CCCH zinc finger domain compared to a CCHC domain of kinetoplastid proteins. Metallomics. 2012; 4(5):433-40. DOI: 10.1039/c2mt00176d. View

Michels P, Bringaud F, Herman M, Hannaert V . Metabolic functions of glycosomes in trypanosomatids. Biochim Biophys Acta. 2006; 1763(12):1463-77. DOI: 10.1016/j.bbamcr.2006.08.019. View

Kirschner M . The meaning of systems biology. Cell. 2005; 121(4):503-504. DOI: 10.1016/j.cell.2005.05.005. View

Andrade J, Murta S . Functional analysis of cytosolic tryparedoxin peroxidase in antimony-resistant and -susceptible Leishmania braziliensis and Leishmania infantum lines. Parasit Vectors. 2014; 7:406. PMC: 4261743. DOI: 10.1186/1756-3305-7-406. View

Brito N, Rabello A, Cota G . Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review. PLoS One. 2017; 12(9):e0184777. PMC: 5604971. DOI: 10.1371/journal.pone.0184777. View

Kunkel E . Systems biology in drug discovery. Conf Proc IEEE Eng Med Biol Soc. 2007; 2006:37. DOI: 10.1109/IEMBS.2006.259390. View

10.

Tessarollo N, Andrade J, Moreira D, Murta S . Functional analysis of iron superoxide dismutase-A in wild-type and antimony-resistant Leishmania braziliensis and Leishmania infantum lines. Parasitol Int. 2014; 64(2):125-9. DOI: 10.1016/j.parint.2014.11.001. View

11.

Ibrahim M, Mahdi M, Bereir R, Giha R, Wasunna C . Evolutionary conservation of RNA editing in the genus Leishmania. Infect Genet Evol. 2008; 8(3):378-80. DOI: 10.1016/j.meegid.2007.12.009. View

12.

Mukherjee A, Padmanabhan P, Singh S, Roy G, Girard I, Chatterjee M . Role of ABC transporter MRPA, gamma-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. J Antimicrob Chemother. 2007; 59(2):204-11. DOI: 10.1093/jac/dkl494. View

13.

Breitling R . What is systems biology?. Front Physiol. 2011; 1:9. PMC: 3059953. DOI: 10.3389/fphys.2010.00009. View

14.

Wyllie S, Vickers T, Fairlamb A . Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrob Agents Chemother. 2008; 52(4):1359-65. PMC: 2292513. DOI: 10.1128/AAC.01563-07. View

15.

Lynn M, McMaster W . Leishmania: conserved evolution--diverse diseases. Trends Parasitol. 2008; 24(3):103-5. DOI: 10.1016/j.pt.2007.11.006. View

16.

Moreira D, Xavier M, Murta S . Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects. Mem Inst Oswaldo Cruz. 2018; 113(12):e180377. PMC: 6251480. DOI: 10.1590/0074-02760180377. View

17.

Noble D . Claude Bernard, the first systems biologist, and the future of physiology. Exp Physiol. 2007; 93(1):16-26. DOI: 10.1113/expphysiol.2007.038695. View

18.

Kumar A, Sisodia B, Misra P, Sundar S, Shasany A, Dube A . Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani. Br J Clin Pharmacol. 2010; 70(4):609-17. PMC: 2950996. DOI: 10.1111/j.1365-2125.2010.03716.x. View

19.

Maarouf M, de Kouchkovsky Y, Brown S, Petit P . In vivo interference of paromomycin with mitochondrial activity of Leishmania. Exp Cell Res. 1997; 232(2):339-48. DOI: 10.1006/excr.1997.3500. View

20.

Mandal S, Maharjan M, Singh S, Chatterjee M, Madhubala R . Assessing aquaglyceroporin gene status and expression profile in antimony-susceptible and -resistant clinical isolates of Leishmania donovani from India. J Antimicrob Chemother. 2010; 65(3):496-507. DOI: 10.1093/jac/dkp468. View