冈比亚西部恶性疟原虫中低复杂度多基因组感染和唾液酸非依赖入侵途径的近期增加。

Recent increase in low complexity polygenomic infections and sialic acid-independent invasion pathways in Plasmodium falciparum from Western Gambia.

机构信息

Medical Research Council Unit The Gambia at London, School of Hygiene and Tropical Medicine, Banjul, The Gambia.

West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.

出版信息

Parasit Vectors. 2023 Aug 31;16(1):309. doi: 10.1186/s13071-023-05929-4.

DOI:10.1186/s13071-023-05929-4

PMID:37653544

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10472613/

Abstract

BACKGROUND

The malaria parasite Plasmodium falciparum utilizes multiple alternative receptor-ligand interactions for the invasion of human erythrocytes. While some P. falciparum clones make use of sialic acid (SA) residues on the surface of the human glycophorin receptors to invade the erythrocyte, others use alternative receptors independent of sialic acid residues. We hypothesized that over the years, intensified malaria control interventions and declining prevalence in The Gambia have resulted in a selection of parasites with a dominant invasion pathways and ligand expression profiles.

METHODS

Blood samples were collected from 65 malaria-infected participants with uncomplicated malaria across 3 years (2015, 2016, and 2021). Genetic diversity was determined by genotyping the merozoite surface protein 2 (msp2) polymorphic gene of P. falciparum. Erythrocyte invasion phenotypes were determined using neuraminidase, trypsin, and chymotrypsin enzymes, known to cleave different receptors from the surface of the erythrocyte. Schizont-stage transcript levels were obtained for a panel of 6 P. falciparum invasion ligand genes (eba175, eba181, Rh2b, Rh4, Rh5, and clag2) using 48 successfully cultured isolates.

RESULTS

Though the allelic heterozygosity of msp2 repeat region decreased as expected with reduced transmission, there was an increase in infections with more than a single msp2 allelotype from 2015 to 2021. The invasion phenotypes of these isolates were mostly SA independent with a continuous increase from 2015 to 2021. Isolates from 2021 were highly inhibited by chymotrypsin treatment compared to isolates from 2015 and 2016. Higher invasion inhibition for 2021 isolates was further obtained following erythrocyte treatment with a combination of chymotrypsin and trypsin. The transcript levels of invasion ligand genes varied across years. However, levels of clag2, a rhoptry-associated protein, were higher in 2015 and 2016 isolates than in 2021 isolates, while Rh5 levels were higher in 2021 compared to other years.

CONCLUSIONS

Overall, these findings suggest increasing mixed infections with an increase in the use of sialic-acid independent invasion pathways by P. falciparum clinical isolates in the Western part of Gambia.

摘要

背景

疟原虫恶性疟原虫利用多种替代受体-配体相互作用入侵人红细胞。虽然一些恶性疟原虫克隆利用人血影蛋白受体表面的唾液酸（SA）残基入侵红细胞，但其他克隆利用与 SA 残基无关的替代受体。我们假设，多年来，冈比亚强化疟疾控制干预措施和患病率下降导致了具有主要入侵途径和配体表达谱的寄生虫选择。

方法

在 3 年（2015 年、2016 年和 2021 年）内，从 65 名患有单纯性疟疾的疟疾感染参与者中采集血液样本。通过基因分型恶性疟原虫的裂殖体表面蛋白 2（msp2）多态性基因，确定遗传多样性。使用神经氨酸酶、胰蛋白酶和糜蛋白酶酶来确定红细胞入侵表型，这些酶已知可以从红细胞表面切割不同的受体。使用 48 个成功培养的分离株，获得了一组 6 个恶性疟原虫入侵配体基因（eba175、eba181、Rh2b、Rh4、Rh5 和 clag2）的合子期转录水平。

结果

尽管 msp2 重复区的等位基因杂合性随着传播的减少而降低，但从 2015 年到 2021 年，具有多个 msp2 等位基因的感染增加。这些分离株的入侵表型主要与 SA 无关，从 2015 年到 2021 年连续增加。与 2015 年和 2016 年的分离株相比，2021 年的分离株在胰蛋白酶处理后受到高度抑制。在用胰蛋白酶和糜蛋白酶联合处理红细胞后，进一步获得了对 2021 年分离株的更高入侵抑制作用。入侵配体基因的转录水平随年份而变化。然而，在 2015 年和 2016 年的分离株中，与 2021 年分离株相比，rhoptry 相关蛋白 clag2 的水平较高，而 Rh5 的水平在 2021 年高于其他年份。