AMINO ACID MUTATIONS IN PLASMODIUM VIVAX DHFR AND DHPS FROM SEVERAL GEOGRAPHICAL REGIONS AND SUSCEPTIBILITY TO ANTIFOLATE DRUGS

Abstract Background Malaria causes major public health problems globally and drug resistance hinders its control and elimination. Molecular markers associated with drug resistance are considered as a beneficial tool to monitor the disease trends, evolution and distribution so as to help improve drug policy. Methods We collected 148 Plasmodium falciparum and 20 Plasmodium vivax isolates imported into Hangzhou city, China between 2014 and 2019. k13 gene of P. falciparum and k12 of P. vivax were sequenced. Polymorphisms and prevalence of k13 and k12 were analyzed. Results Most (98.65%, 146/148) P. falciparum infections were imported from Africa, and half P. vivax cases came from Africa and the other half from Asia. Nucleotide mutation prevalence was 2.03% (3/148) and the proportion of amino acid mutations was 0.68% (1/148). The amino acid mutation, A676S, was observed in an isolate from Nigeria. No mutation of k12 was observed from the parasites from African and Asian countries. Conclusions Limited polymorphism in k13 gene of P. falciparum isolates imported from African countries, but no evidence for the polymorphism of k12 in P. vivax samples from African and Asian countries was found. These results provide information for drug policy update in study region.

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Detection of Amino Acid Mutations in Dihydrofolate Reductase & Dihydro Pteroate Synthase Gene in Plasmodium Vivax Isolates

Journal of Liaquat University of Medical & Health Sciences ◽

10.22442/jlumhs.201920671 ◽

2020 ◽

Vol 19 (02) ◽

pp. 102-108

Keyword(s):

Amino Acid ◽

Plasmodium Vivax ◽

Dihydrofolate Reductase ◽

Amino Acid Mutations

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Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.6.2214-2222.2004 ◽

2004 ◽

Vol 48 (6) ◽

pp. 2214-2222 ◽

Cited By ~ 64

Author(s):

Michael Korsinczky ◽

Katja Fischer ◽

Nanhua Chen ◽

Joanne Baker ◽

Karl Rieckmann ◽

...

Keyword(s):

Amino Acid ◽

Binding Site ◽

Plasmodium Vivax ◽

Binding Sites ◽

Protein Sequence ◽

Three Dimensional ◽

Specific Amino Acid ◽

Dihydropteroate Synthase ◽

Contact Residues ◽

Amino Acid Mutations

ABSTRACT Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

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Geographical Distribution of Amino Acid Mutations in Plasmodium vivax DHFR and DHPS from Malaria Endemic Areas of Thailand

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.2008.78.462 ◽

2008 ◽

Vol 78 (3) ◽

pp. 462-467 ◽

Cited By ~ 27

Author(s):

Kanchana Rungsihirunrat ◽

Kesara Na-Bangchang ◽

Mathirut Mungthin ◽

Carol Hopkins Sibley

Keyword(s):

Amino Acid ◽

Plasmodium Vivax ◽

Geographical Distribution ◽

Endemic Areas ◽

Amino Acid Mutations

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Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia

Malaria Journal ◽

10.1186/s12936-016-1543-8 ◽

2016 ◽

Vol 15 (1) ◽

Cited By ~ 8

Author(s):

Naowarat Saralamba ◽

Supatchara Nakeesathit ◽

Mayfong Mayxay ◽

Paul N. Newton ◽

Lyda Osorio ◽

...

Keyword(s):

Amino Acid ◽

Plasmodium Vivax ◽

Geographic Distribution ◽

Lao Pdr ◽

Amino Acid Mutations

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Genetic Variation and Evolution of the 2019 Novel Coronavirus

Public Health Genomics ◽

10.1159/000513530 ◽

2021 ◽

pp. 1-13

Author(s):

Salvatore Dimonte ◽

Muhammed Babakir-Mina ◽

Taib Hama-Soor ◽

Salar Ali

Keyword(s):

Amino Acid ◽

Receptor Binding ◽

Rapid Evolution ◽

Single Amino Acid ◽

Angiotensin Converting Enzyme 2 ◽

New Type ◽

Amino Acid Mutations ◽

Host Infection ◽

Human Coronaviruses ◽

Novel Coronavirus

Introduction: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. Methods: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. Results: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. Discussion/Conclusion: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

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Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

Gut Pathogens ◽

10.1186/s13099-021-00419-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Zhijing Xue ◽

Yuanhai You ◽

Lihua He ◽

Yanan Gong ◽

Lu Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Amino Acid ◽

Chinese Population ◽

Statistical Difference ◽

Variable Region ◽

Repeat Region ◽

Geographical Regions ◽

H Pylori ◽

Epiya Motifs

Abstract Background The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

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Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 Shows Recombination and Signatures of Balancing Selection

Genes ◽

10.3390/genes12010029 ◽

2020 ◽

Vol 12 (1) ◽

pp. 29

Author(s):

Lilia González-Cerón ◽

José Cebrián-Carmona ◽

Concepción M. Mesa-Valle ◽

Federico García-Maroto ◽

Frida Santillán-Valenzuela ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

Plasmodium Vivax ◽

Nucleotide Diversity ◽

Protective Antigen ◽

Balancing Selection ◽

Southern Mexico ◽

Exon 2 ◽

Exon 1 ◽

Tajima’S D

Plasmodium vivax Cysteine-Rich Protective Antigen (CyRPA) is a merozoite protein participating in the parasite invasion of human reticulocytes. During natural P. vivax infection, antibody responses against PvCyRPA have been detected. In children, low anti-CyRPA antibody titers correlated with clinical protection, which suggests this protein as a potential vaccine candidate. This work analyzed the genetic and amino acid diversity of pvcyrpa in Mexican and global parasites. Consensus coding sequences of pvcyrpa were obtained from seven isolates. Other sequences were extracted from a repository. Maximum likelihood phylogenetic trees, genetic diversity parameters, linkage disequilibrium (LD), and neutrality tests were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. In 22 sequences from Southern Mexico, two synonymous and 21 nonsynonymous mutations defined nine private haplotypes. These parasites had the highest LD-R2 index and the lowest nucleotide diversity compared to isolates from South America or Asia. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity and Rm values than those of exon-2. Exon-1 had significant positive values for Tajima’s D, β-α values, and for the Z (HA: dN > dS) and MK tests. These patterns were similar for parasites of different origin. The polymorphic amino acid residues at PvCyRPA resembled the conformational B-cell peptides reported in PfCyRPA. Diversity at pvcyrpa exon-1 is caused by mutation and recombination. This seems to be maintained by balancing selection, likely due to selective immune pressure, all of which merit further study.

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