Expression of Ascaris lumbricoides putative virulence-associated genes when infecting a human host

Norashikin Mohd-Shaharuddin,Yvonne Ai Lian Lim,Sheila Nathan,Romano Ngui

doi:10.1186/s13071-021-04680-y

Norashikin Mohd-Shaharuddin, Yvonne Ai Lian Lim + Show 2 more

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https://doi.org/10.1186/s13071-021-04680-y

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Abstract

BackgroundAscaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. It is suggested that helminths are capable of evading and manipulating the host immune system through the release of a spectrum of worm proteins which underpins their long-term survival in the host. We hypothesise that the worm overexpresses these proteins when infecting adults compared to children to cirvumvent the more robust defence mechanisms of adults. However, little is known about the parasite’s genes and encoded proteins involved during A. lumbricoides infection. Hence, this study was conducted to assess the expression profile of putative virulence-associated genes during an active infection of adults and children.MethodsIn this study, quantitative PCR was performed to evaluate the expression profile of putative virulence-associated genes in A. lumbricoides isolated from infected children and adults. The study was initiated by collecting adult worms expelled from adults and children following anthelminthic treatment. High-quality RNA was successfully extracted from each of six adult worms expelled by three adults and three children, respectively. Eleven putative homologues of helminth virulence-associated genes reported in previous studies were selected, primers were designed and specific amplicons of A. lumbricoides genes were noted. The expression profiles of these putative virulence-associated genes in A. lumbricoides from infected adults were compared to those in A. lumbricoides from infected children.ResultsThe putative virulence-associated genes VENOM, CADHERIN and PEBP were significantly upregulated at 166-fold, 13-fold and fivefold, respectively, in adults compared to children. Conversely, the transcription of ABA-1 (fourfold), CATH-L (threefold) and INTEGRIN (twofold) was significantly suppressed in A. lumbricoides from infected adults.ConclusionsOn the basis of the expression profile of the putative virulence-associated genes, wepropose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions.Graphical

Highlights

Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally
On the basis of the expression profile of the putative virulence-associated genes, we propose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions
Ascaris suum is a closely related species of A. lumbricoides, and in this study we proposed that homologues of A. suum virulence genes [21] exist in A. lumbricoides; these genes are referred to as putative A. lumbricoides virulence-associated genes

Summary

Introduction

Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. Little is known about the parasite’s genes and encoded proteins involved during A. lumbricoides infection. Ascaris lumbricoides is a major causative agent of soiltransmitted helminth (STH) infections worldwide. According to the Global Burden of Diseases Study, in 2019, a total of 446 million cases of A. lumbricoides infection were reported globally, involving both males and females [1]. In Malaysia, the incidence of A. lumbricoides infection is significant and highly prevalent among the indigenous (Orang Asli) communities [2,3,4]. A previous local study among the Orang Asli school children of Peninsular Malaysia reported that reinfection with A. lumbricoides at 6 months post-treatment was close to the baseline situation [8]. In eastern Indonesia, a study described that the prevalence of A. lumbricoides was significantly higher than the baseline prevalence 34 months after the cessation of the mass drug administration programme [9], while in the People’s Republic of China, re-infection with A. lumbricoides was reported as early as 4 months post-drug administration [10]

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