Molecular Surveillance and Ex Vivo Drug Susceptibilities of Plasmodium vivax Isolates From the China–Myanmar Border

Drug resistance in Plasmodium vivax may pose a challenge to malaria elimination. Previous studies have found that P. vivax has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the ex vivo drug susceptibilities of P. vivax isolates from the China–Myanmar border and genetic variations of resistance-related genes. A total of 46 P. vivax clinical isolates were assessed for ex vivo susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC50 (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC50 values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvmrp1 (P. vivax multidrug resistance protein 1), pvdhfr (P. vivax dihydrofolate reductase), and pvdhps (P. vivax dihydropteroate synthase) were determined by PCR and sequencing. Pvmdr1 had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. Pvmrp1 had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several pvdhfr and pvdhps mutations were relatively frequent in the studied parasite population. The pvmdr1 G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of P. vivax isolates resistant to certain antimalarial drugs at the China–Myanmar border, which demands continuous surveillance for drug resistance.

Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.

Antibacterial Activity of Ethyl Acetate Extract of Endophytic Fungus (Paraconiothyrium Brasiliense) Through Targeting Pathogenesis Related Dihydropteroate Synthase (DHPS)

Endophytic fungi are innumerable sources of bioactive metabolites with various biomedical applications. Hence, this study was aimed to isolate and identify the endophytic fungus Paraconiothyrium brasiliense (PB) from the fruit of Capsicum annuum and evaluated their biochemical, antimicrobial, antioxidant, cell viability, and cytotoxicity behavior. Results showed that ethyl acetate extract (EAE) of PE contains flavonoid (31.53 ± 0.9 mg of QE/g of extract) and phenolic (2.59 ± 0.06 mg of GAE/g of extract). The PB-EAE showed significant antioxidant activity in terms of free radicals such as DPPH, ABTS, and Fe3+ scavenging. The antioxidant potential of PB-EAE reflects in normal cell viability and anticancer activity against prostate cancer (PC3) cells. The bacterial inhibitory activity of PB-EAE was equal to commercial antibiotic tetracycline hydrochloride (TCH). Further, GC-MS analysis confirmed the presence of volatile molecules such as o-cymene (CH3C6H4CH(CH3)2), dipentene (C10H16), γ-terpinene (C10H16), 4-carvomenthenol (C10H18O), heneicosane (CH3(CH2)19CH3), 2,5-piperazinedione (C4H6N2O2). Also, molecular docking analysis demonstrated the significant interactions between the compounds of PB-EAE and Dihydropteroate Synthase (Protein ID:5JQ9; DHPS). This study revealed that endophytic P. brasiliense from Capsicum annuum could be a novel source for the isolation of antimicrobials.

The Drug Resistance of Plasmodium falciparum and P. vivax in Iran: A Review Article

Background: One of the main obstacles to malaria control in the world has been the emergence of resistance in Plasmodium falciparum to chloroquine and other antimalarial drugs. This study aimed to review studies in Iran on resistance in P. falciparum and P. vivax to drugs, and to reveal the mechanisms and molecular markers of resistance of these two species. Methods: The databases of PubMed, Scopus, Google Scholar, Magiran, and reputable Iranian journals were searched to find published studies on the resistance in P. falciparum and P. vivax to antimalarial drugs in Iran. Results: There is a significant relationship between resistance to chloroquine in P. falciparum and the emergence of K76T mutation in the P. falciparum chloroquineresistance transporter gene in Iran. Resistance to sulfadoxine-pyrimethamine (SP) in P. falciparum is also significantly associated with the development of mutations in the dihydrofolate reductase and dihydropteroate synthase genes. Resistance to chloroquine in P. vivax has not been reported in Iran and it is used as a first-line treatment for P. vivax malaria. Conclusion: P. falciparum has become resistant to chloroquine in different regions of Iran and is not currently used to treat malaria. Besides, cases have emerged of P. falciparum resistance to SP in different parts of southern Iran, and SP is not administered alone for treating P. falciparum.