Dataset Information

Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria.

ABSTRACT: Parasitic nematode infections cause debilitating diseases and impede economic productivity. Antinematode chemotherapies are fundamental to modern medicine and are also important for industries including agriculture, aquaculture and animal health. However, the lack of suitable treatments for some diseases and the rise of nematode resistance to many available therapies necessitates the discovery and development of new drugs. Here, marine epiphytic bacteria represent a promising repository of newly discovered antinematode compounds. Epiphytic bacteria are ubiquitous on marine surfaces where they are under constant pressure of grazing by bacterivorous predators (e.g., protozoans and nematodes). Studies have shown that these bacteria have developed defense strategies to prevent grazers by producing toxic bioactive compounds. Although several active metabolites against nematodes have been identified from marine bacteria, drug discovery from marine microorganisms remains underexplored. In this review, we aim to provide further insight into the need and potential for marine epiphytic bacteria to become a new source of antinematode drugs. We discuss current and emerging strategies, including culture-independent high throughput screening and the utilization of Caenorhabditis elegans as a model target organism, which will be required to advance antinematode drug discovery and development from marine microbial sources.

SUBMITTER: Salikin NH

PROVIDER: S-EPMC7764037 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria.

Salikin Nor Hawani NH Nappi Jadranka J Majzoub Marwan E ME Egan Suhelen S

Microorganisms 20201211 12

Parasitic nematode infections cause debilitating diseases and impede economic productivity. Antinematode chemotherapies are fundamental to modern medicine and are also important for industries including agriculture, aquaculture and animal health. However, the lack of suitable treatments for some diseases and the rise of nematode resistance to many available therapies necessitates the discovery and development of new drugs. Here, marine epiphytic bacteria represent a promising repository of newly ...[more]

PMID: 33322253

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Project description:Despite the progress made in immunization and drug development, so far there are no prophylactic vaccines and effective therapies for many viral infections, including infections caused by coronaviruses. In this regard, the search for new antiviral substances continues to be relevant, and the enormous potential of marine resources are a stimulus for the study of marine compounds with antiviral activity in experiments and clinical trials. The highly pathogenic human coronaviruses-severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) remain a serious threat to human health. In this review, the authors hope to bring the attention of researchers to the use of biologically active substances of marine origin as potential broad-spectrum antiviral agents targeting common cellular pathways and various stages of the life cycle of different viruses, including coronaviruses. The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to June 2020) and keywords such as 'coronaviruses', 'marine organisms', 'biologically active substances', 'antiviral drugs', 'SARS-CoV', 'MERS-CoV', 'SARS-CoV-2', '3CLpro', 'TMPRSS2', 'ACE2'. After obtaining all reports from the databases, the papers were carefully analysed in order to find data related to the topic of this review (98 references). Biologically active substances of marine origin, such as flavonoids, phlorotannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, lipids and others substances, can affect coronaviruses at the stages of penetration and entry of the viral particle into the cell, replication of the viral nucleic acid and release of the virion from the cell; they also can act on the host's cellular targets. These natural compounds could be a vital resource in the fight against coronaviruses.

Project description:Heme is an essential molecule for vast majority of organisms serving as a prosthetic group for various hemoproteins. Although most organisms synthesize heme from 5-aminolevulinic acid through a conserved heme biosynthetic pathway composed of seven consecutive enzymatic reactions, nematodes are known to be natural heme auxotrophs. The completely sequenced Caenorhabditis elegans genome, for example, lacks all seven genes for heme biosynthesis. However, genome/transcriptome sequencing of Strongyloides venezuelensis, an important model nematode species for studying human strongyloidiasis, indicated the presence of a gene for ferrochelatase (FeCH), which catalyzes the terminal step of heme biosynthesis, whereas the other six heme biosynthesis genes are apparently missing. Phylogenetic analyses indicated that nematode FeCH genes, including that of S. venezuelensis (SvFeCH) have a fundamentally different evolutionally origin from the FeCH genes of non-nematode metazoa. Although all non-nematode metazoan FeCH genes appear to be inherited vertically from an ancestral opisthokont, nematode FeCH may have been acquired from an alpha-proteobacterium, horizontally. The identified SvFeCH sequence was found to function as FeCH as expected based on both in vitro chelatase assays using recombinant SvFeCH and in vivo complementation experiments using an FeCH-deficient strain of Escherichia coli. Messenger RNA expression levels during the S. venezuelensis lifecycle were examined by real-time RT-PCR. SvFeCH mRNA was expressed at all the stages examined with a marked reduction at the infective third-stage larvae. Our study demonstrates the presence of a bacteria-like FeCH gene in the S. venezuelensis genome. It appeared that S. venezuelensis and some other animal parasitic nematodes reacquired the once-lost FeCH gene. Although the underlying evolutionary pressures that necessitated this reacquisition remain to be investigated, it is interesting that the presence of FeCH genes in the absence of other heme biosynthesis genes has been reported only for animal pathogens, and this finding may be related to nutritional availability in animal hosts.

Dataset Information

Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria.

Publications

Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria.

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