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drug resistance

Predicting Drug Resistance Using Deep Mutational Scanning

May 14, 2020 - 13:35 -- Open Access
Author(s): 
Pines G, Fankhauser RG, Eckert CA
Reference: 
Molecules. 2020 May 11;25(9):E2265

Drug resistance is a major healthcare challenge, resulting in a continuous need to develop new inhibitors. The development of these inhibitors requires an understanding of the mechanisms of resistance for a critical mass of occurrences.

NOT Open Access | Structure and drug resistance of the Plasmodium falciparum transporter PfCRT

May 13, 2020 - 13:48 -- NOT Open Access
Author(s): 
Jonathan Kim, Yong Zi Tan, Filippo Mancia, et al.
Reference: 
Drug Deliv Transl Res. 2020 May 7

The emergence and spread of drug-resistant Plasmodium falciparum impedes global efforts to control and eliminate malaria. For decades, treatment of malaria has relied on chloroquine (CQ), a safe and affordable 4-aminoquinoline that was highly effective against intra-erythrocytic asexual blood-stage parasites, until resistance arose in Southeast Asia and South America and spread worldwide1.

Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China

April 27, 2020 - 13:22 -- Open Access
Author(s): 
Wang X, Ruan W, Zhou S, Feng X, Yan H, Huang F
Reference: 
BMC Infect Dis. 2020 Apr 25;20(1):307

Plasmodium vivax is the most widely distributed malaria parasite, and its drug resistance poses unique challenges to malaria elimination. The Greater Mekong Subregion (GMS) is known as the global epicenter of multidrug resistance. Surveillance of molecular markers associated with drug resistance in this area will help to inform drug policy.

Role of a Concentration Gradient in Malaria Drug Resistance Evolution: A Combined within- and between-Hosts Modelling Approach

April 13, 2020 - 15:27 -- Open Access
Author(s): 
Romphosri S, Changruenngam S, Chookajorn T, Modchang C
Reference: 
Sci Rep. 2020 Apr 10;10(1):6219

Resistance to antimalarial drugs is currently a growing public health problem, resulting in more cases with treatment failure. Although previous studies suggested that a concentration gradient facilitates the antibiotic resistance evolution in bacteria, no attempt has been made to investigate the roles of a concentration gradient in malaria drug resistance. Unlike the person-to-person mode of transmission of bacteria, the malaria parasites need to switch back and forth between the human and mosquito hosts to complete the life cycle and to spread the resistant alleles.

NOT Open Access | Plasmodium vivax drug resistance markers: Genetic polymorphisms and mutation patterns in isolates from Malaysia

March 25, 2020 - 14:53 -- NOT Open Access
Author(s): 
Cheong FW, Dzul S, Fong MY, Lau YL, Ponnampalavanar S
Reference: 
Acta Trop. 2020 Mar 20:105454

Transmission of Plasmodium vivax still persist in Malaysia despite the government's aim to eliminate malaria in 2020. High treatment failure rate of chloroquine monotherapy was reported recently. Hence, parasite drug susceptibility should be kept under close monitoring. Mutation analysis of the drug resistance markers is useful for reconnaissance of anti-malarial drug resistance. Hitherto, information on P. vivax drug resistance marker in Malaysia are limited.

NOT Open Access | A histone methyltransferase inhibitor can reverse epigenetically acquired drug resistance in the malaria parasite Plasmodium falciparum

March 19, 2020 - 09:09 -- NOT Open Access
Author(s): 
Chan A, Dziedziech A, Kirkman LA, Deitsch KW, Ankarklev J
Reference: 
Antimicrob Agents Chemother. 2020 Mar 16. pii: AAC.02021-19

Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically.

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

February 24, 2020 - 13:56 -- Open Access
Author(s): 
Abdelrahim O. Mohamed, Maazza Hussien, Amal Mohamed, Abdelmaroof Suliman, Nuha S. Elkando, Hanadi Abdelbagi, Elfatih M. Malik, Mohammed H. Abdelraheem and Muzamil Mahdi Abdel Hamid
Reference: 
Malaria Journal 2020 19:78, 18 February 2020

Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether–lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan.

NOT Open Access | In-silico profiling and structural insights into the impact of nSNPs in the P. falciparum acetyl-CoA transporter gene to understand the mechanism of drug resistance in malaria

January 14, 2020 - 16:24 -- NOT Open Access
Author(s): 
Sardar R, Katyal N, Ahamad S, Jade DD, Ali S, Gupta D
Reference: 
Journal of Biomolecular Structure and Dynamics, 2020 Jan 6:1-23

The continuous emergence of resistance to the available drugs poses major constraints in the development of effective therapeutics against Malaria. The Malaria drug resistance has been attributed to be the manifestation of numerous factors. For example, mutations in the parasite transporter protein acetyl-CoA transporter (Pfact) can remarkably affect its uptake affinity for a drug molecule against malaria, and hence enhance its susceptibility to resistance.

Not Open Access | Structure and drug resistance of the Plasmodium falciparum transporter PfCRT

December 16, 2019 - 16:15 -- NOT Open Access
Author(s): 
Jonathan Kim, Yong Zi Tan, Filippo Mancia, et al.
Reference: 
Nature volume 576, pages315–320(2019)

The emergence and spread of drug-resistant Plasmodium falciparum impedes global efforts to control and eliminate malaria. For decades, treatment of malaria has relied on chloroquine (CQ), a safe and affordable 4-aminoquinoline that was highly effective against intra-erythrocytic asexual blood-stage parasites, until resistance arose in Southeast Asia and South America and spread worldwide1.

The genomic architecture of antimalarial drug resistance

November 26, 2019 - 20:17 -- Open Access
Author(s): 
Annie N Cowell, Elizabeth A Winzeler
Reference: 
Briefings in Functional Genomics, Volume 18, Issue 5, September 2019, Pages 314–328

Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person’s bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes.

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