Evaluating the Genetic Capacity of Mycoplasmas for Coenzyme A Biosynthesis in a Search for New Anti-mycoplasma Targets

Mycoplasmas are responsible for a wide range of disease states in both humans and animals, in which their parasitic lifestyle has allowed them to reduce their genome sizes and curtail their biosynthetic capabilities. The subsequent dependence on their host offers a unique opportunity to explore pathways for obtaining and producing cofactors – such as coenzyme A (CoA) – as possible targets for the development of new anti-mycoplasma agents. CoA plays an essential role in energy and fatty acid metabolism and is required for membrane synthesis. However, our current lack of knowledge of the relevance and importance of the CoA biosynthesis pathway in mycoplasmas, and whether it could be bypassed within their pathogenic context, prevents further exploration of the potential of this pathway. In the universal, canonical CoA biosynthesis pathway, five enzymes are responsible for the production of CoA. Given the inconsistent presence of the genes that code for these enzymes across Mycoplasma genomes, this study set out to establish the genetic capacity of mycoplasmas to synthesize their own CoA de novo. Existing functional annotations and sequence, family, motif, and domain analysis of protein products were used to determine the existence of relevant genes in Mycoplasma genomes. We found that most Mycoplasma species do have the genetic capacity to synthesize CoA, but there was a differentiated prevalence of these genes across species. Phylogenetic analysis indicated that the phylogenetic position of a species could not be used to predict its enzyme-encoding gene combinations. Despite this, the final enzyme in the biosynthesis pathway – dephospho-coenzyme A kinase (DPCK) – was found to be the most common among the studied species, suggesting that it has the most potential as a target in the search for new broad-spectrum anti-mycoplasma agents.

A world of viruses nested within parasites: Unraveling viral diversity within parasitic flatworms (Platyhelminthes)

Because parasites have an inextricable relationship with their host, they have the potential to serve as viral reservoirs or facilitate virus host-shifts. Yet, little is known about viruses infecting parasitic hosts except for blood-feeding arthropods that are well-known vectors of zoonotic viruses. Herein we uncover viruses of flatworms (Phylum Platyhelminthes, group Neodermata) that specialize in parasitizing vertebrates and their ancestral free-living relatives. We discovered 115 novel viral sequences, including 1 in Macrostomorpha, 5 in Polycladida, 44 in Tricladida, 1 in Monogenea, 15 in Cestoda and 49 in Trematoda, through data mining. The majority of newly identified viruses constitute novel families or genera. Phylogenetic analyses show that the virome of flatworms changed dramatically during the transition of Neodermatans to a parasitic lifestyle. Most Neodermatan viruses seem to co-diversify with their host , with the exception of rhabdoviruses which may switch host more often, based on phylogenetic relationships. Neodermatan rhabodviruses also have an ancestral position to vertebrate-associated viruses, including Lyssaviruses, suggesting that vertebrate rhabdoviruses emerged from a flatworm rhabdovirus in a parasitized host. This study reveals an extensive diversity of viruses in Platyhelminthes and highlights the need to evaluate the role of viral infection in flatworm-associated diseases.

Traits of a mussel transmissible cancer are reminiscent of a parasitic life style

Some cancers have evolved the ability to spread from host to host by transmission of cancerous cells. These rare biological entities can be considered parasites with a host-related genome. Still, we know little about their specific adaptation to a parasitic lifestyle. MtrBTN2 is one of the few lineages of transmissible cancers known in the animal kingdom. Reported worldwide, MtrBTN2 infects marine mussels. We isolated MtrBTN2 cells circulating in the hemolymph of cancerous mussels and investigated their phenotypic traits. We found that MtrBTN2 cells had remarkable survival capacities in seawater, much higher than normal hemocytes. With almost 100% cell survival over three days, they increase significantly their chances to infect neighboring hosts. MtrBTN2 also triggered an aggressive cancerous process: proliferation in mussels was ~ 17 times higher than normal hemocytes (mean doubling time of ~ 3 days), thereby favoring a rapid increase of intra-host population size. MtrBTN2 appears to induce host castration, thereby favoring resources re-allocation to the parasites and increasing the host carrying capacity. Altogether, our results highlight a series of traits of MtrBTN2 consistent with a marine parasitic lifestyle that may have contributed to the success of its persistence and dissemination in different mussel populations across the globe.

A morphological and molecular reinvestigation of Janickina pigmentifera (Grassi, 1881) Chatton 1953 – an amoebozoan parasite of arrow-worms (Chaetognatha)

Amoebozoan parasites of arrow-worms (Chaetognatha) were isolated from their hosts living in plankton of the Bay of Villefranche (Mediterranean Sea). Based on the light microscopic characters, the amoebae were identified as Janickina pigmentifera (Grassi, 1881) by their limax locomotive form and due to the presence of the intracellular symbiont, Perkinsela amoebae, surrounded by a layer of pigment granules. Sequences of the 18S rRNA gene of both J. pigmentifera and its symbiont were obtained for the first time. The molecular phylogenetic analyses of 18S rRNA gene placed J. pigmentifera within the genus Neoparamoeba, a taxon also characterized by the presence of a symbiont, known as Perkinsela amoebae-like organism (PLO). The 18S rRNA gene sequence of P. amoebae from J. pigmentifera grouped with the sequences of 18S rRNA genes of PLOs from Neoparamoeba branchiphila and Neoparamoeba invadens. The first photo documentation of the light microscopic features of J. pigmentifera, such as locomotive form, the morphology of the nucleus and P. amoebae have been provided. The new results support the affinity of J. pigmentifera with the family Paramoebidae suggested previously based on the presence of PLO. In contrast to Janickina, typical members of Paramoebidae (Neoparamoeba and Paramoeba) have a flattened, dactylopodial locomotive form. This discrepancy in morphology can be explained by the obligate parasitic lifestyle of Janickina.

The Virosphere

This chapter provides an overview of the virosphere. Viruses are fundamentally different from all other organisms, including other microbes. They are honed to the bare essentials required to survive, albeit through a parasitic lifestyle. They cannot do anything on their own, so they are obliged to penetrate a living cell and take control. The weakening of the host cells which viruses inhabit can in some cases have unexpected and bizarre effects on the infected cells and on the animal or plant hosting the virus. One famous example of such an effect occurred in Holland in the seventeenth century, when beautiful variegated tulip flowers were first cultivated, causing what became known as tulipomania. The chapter then considers three theories on the origin of viruses: the progressive, the regressive, and the virus-first theories. It also explains how viruses spread, looking at food poisoning, coughs and sneezes, and also man-made virus transmission and mother-to-child transmission.

On the role of dauer in the adaptation of nematodes to a parasitic lifestyle

Nematodes are presumably the most abundant Metazoa on Earth, and can even be found in some of the most hostile environments of our planet. Various types of hypobiosis evolved to adapt their life cycles to such harsh environmental conditions. The five most distal major clades of the phylum Nematoda (Clades 8–12), formerly referred to as the Secernentea, contain many economically relevant parasitic nematodes. In this group, a special type of hypobiosis, dauer, has evolved. The dauer signalling pathway, which culminates in the biosynthesis of dafachronic acid (DA), is intensively studied in the free-living nematode Caenorhabditis elegans, and it has been hypothesized that the dauer stage may have been a prerequisite for the evolution of a wide range of parasitic lifestyles among other nematode species. Biosynthesis of DA is not specific for hypobiosis, but if it results in exit of the hypobiotic state, it is one of the main criteria to define certain behaviour as dauer. Within Clades 9 and 10, the involvement of DA has been validated experimentally, and dauer is therefore generally accepted to occur in those clades. However, for other clades, such as Clade 12, this has hardly been explored. In this review, we provide clarity on the nomenclature associated with hypobiosis and dauer across different nematological subfields. We discuss evidence for dauer-like stages in Clades 8 to 12 and support this with a meta-analysis of available genomic data. Furthermore, we discuss indications for a simplified dauer signalling pathway in parasitic nematodes. Finally, we zoom in on the host cues that induce exit from the hypobiotic stage and introduce two hypotheses on how these signals might feed into the dauer signalling pathway for plant-parasitic nematodes. With this work, we contribute to the deeper understanding of the molecular mechanisms underlying hypobiosis in parasitic nematodes. Based on this, novel strategies for the control of parasitic nematodes can be developed.

Evidence for a conserved queen-worker genetic toolkit across slave-making ants and their ant hosts

The ecological success of social Hymenoptera (ants, bees, wasps) depends on the division of labour between the queen and workers. Each caste is highly specialized in their respective function in morphology, behaviour and life history traits, such as lifespan and fecundity. Despite strong defences against alien intruders, insect societies are vulnerable to social parasites, such as workerless inquilines or slave-making (dulotic) ants. Here, we investigate whether gene expression varies in parallel ways between slave-making ants and their host ants across five independent origins of ant slavery in the Formicoxenus-group of the ant tribe Crematogastrini. As caste differences are often less pronounced in slave-making ants than non-parasitic ants, we also compare the transcriptomes of queens and workers in these species. We demonstrate a substantial overlap in expression differences between queens and workers across taxa, irrespective of lifestyle. Caste affects the transcriptomes much more profoundly than lifestyle, as indicated by 37 times more genes being linked to caste than to lifestyle and by multiple caste-associated gene modules with strong connectivity. However, several genes and one gene module are linked to the slave-making lifestyle across the independent origins, pointing to some evolutionary convergence. Finally, we do not find evidence for an interaction between caste and lifestyle, indicating that caste differences remain consistent even when species switch to a parasitic lifestyle. Our findings are a strong indication for the existence of a core set of genes whose expression is linked to the queen and worker caste in this ant taxon, supporting the genetic-toolkit hypothesis.

First person – Natalia Mallo

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Natalia Mallo is first author on ‘ Depletion of a Toxoplasma porin leads to defects in mitochondrial morphology and contacts with the endoplasmic reticulum’, published in JCS. Natalia conducted the research described in this article while a Postdoc Research Associate in Lilach Sheiner's lab at Wellcome Centre For Integrative Parasitology, University of Glasgow, UK. She now works in the lab of Santiago Cabaleiro at CETGA (Technological Centre of the Aquaculture Cluster), Ribeira, A Coruña, Spain, where her research interests are related to the study of molecular biology of protozoan parasites. Natalia has a special interest in endosymbiotic organelles, such as the mitochondrion, and aims to elucidate organelle functions that can be related to adaptations to parasitic lifestyle.