Acyl-CoA oxidase ACOX-1 interacts with a peroxin PEX-5 to play roles in larval development of Haemonchus contortus.

Hengzhi Shi,Yi Yang,Chaoqun Yao,Jingru Zhou,Zhao Wang,Xueqiu Chen,Xiaocui Huang,Yimin Yang,Fei Wu,Guangxu Ma,Aifang Du,Cinzia Cantacessi

doi:10.1371/journal.ppat.1009767

Abstract

Hypobiosis (facultative developmental arrest) is the most important life-cycle adaptation ensuring survival of parasitic nematodes under adverse conditions. Little is known about such survival mechanisms, although ascarosides (ascarylose with fatty acid-derived side chains) have been reported to mediate the formation of dauer larvae in the free-living nematode Caenorhabditis elegans. Here, we investigated the role of a key gene acox-1, in the larval development of Haemonchus contortus, one of the most important parasitic nematodes that employ hypobiosis as a routine survival mechanism. In this parasite, acox-1 encodes three proteins (ACOXs) that all show a fatty acid oxidation activity in vitro and in vivo, and interact with a peroxin PEX-5 in peroxisomes. In particular, a peroxisomal targeting signal type1 (PTS1) sequence is required for ACOX-1 to be recognised by PEX-5. Analyses on developmental transcription and tissue expression show that acox-1 is predominantly expressed in the intestine and hypodermis of H. contortus, particularly in the early larval stages in the environment and the arrested fourth larval stage within host animals. Knockdown of acox-1 and pex-5 in parasitic H. contortus shows that these genes play essential roles in the post-embryonic larval development and likely in the facultative arrest of this species. A comprehensive understanding of these genes and the associated β-oxidation cycle of fatty acids should provide novel insights into the developmental regulation of parasitic nematodes, and into the discovery of novel interventions for species of socioeconomic importance.

Highlights

Temporary cessation of development among nematodes in response to certain circumstances or within certain host animals, known as facultative developmental arrest or hypobiosis, is an ability to interrupt the life cycle to survive harsh conditions [1,2,3]
At least five ascarosides, such as asc-C6-MK (C6; ascr#2), asc-ΔC9 (C9; ascr#3), asc-ωC3 (C3; ascr#5), asc-ΔC7-PABA and IC-asc-C5 (C5; icas#9), serve as dauer pheromones and play roles in developmental regulation of C. elegans [15,16,17]. These molecules are sensed by G protein-coupled receptors (GPCRs) of specific chemosensory neurons [16,18,19,20], inhibiting cyclic guanosine monophosphate [21,22], transforming growth factor β (TGF-β) [23,24], and insulin/insulin-like growth factor 1 (IGF-1) [25,26,27], which converge on steroid hormone receptor inactivation for a molecular decision of dauer formation [28,29]
Three transcripts were identified by mapping molecularly cloned sequences to the reference genome of H. contortus, matching two gene loci Hc-acox-1.1 and Hc-acox-1.2 in chromosome IV of this parasitic nematode (Fig 1A)

Summary

Introduction

Temporary cessation of development among nematodes in response to certain circumstances or within certain host animals, known as facultative developmental arrest or hypobiosis, is an ability to interrupt the life cycle to survive harsh conditions [1,2,3]. In parasitic nematodes (e.g., Ancylostomatidae, Ascaridae, Strongyloididae, Trichostrongylidae, Trichonematidae), infective larvae can cease their development at an early parasitic stage in response to seasonal/ host factors, and do not resume their development until conditions become favourable [1,6,7]. Mechanisms underlying such developmental arrest of nematodes and related phenomena have been proposed and investigated for decades [1,2,3], with advanced understanding achieved mostly in the model organism C. elegans [8,9,10,11,12,13]. The genetic basis for such machinery has not yet been elucidated in parasitic nematodes, species of veterinary and medical importance

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