Dataset Information

Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria.

ABSTRACT: Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of the Moroccan Atlantic coast. Only 4 Actinobacteria isolates showing strong predation capability against native or multidrug-resistant Gram-positive or Gram-negative bacteria were identified among 142 isolated potential predatory bacteria. These actinobacterial predators were shown to belong to the Streptomyces genus and to inhibit the growth of various native or multidrug-resistant micro-organisms, including Micrococcus luteus, Staphylococcus aureus (native and methicillin-resistant), and Escherichia coli (native and ampicillin-resistant). Even if no clear correlation could be established between the antibacterial activities of the selected predator Actinobacteria and their predatory activity, we cannot exclude that some specific bio-active secondary metabolites were produced in this context and contributed to the killing and lysis of the bacteria. Indeed, the co-cultivation of Actinobacteria with other bacteria is known to lead to the production of compounds that are not produced in monoculture. Furthermore, the production of specific antibiotics is linked to the composition of the growth media that, in our co-culture conditions, exclusively consisted of the components of the prey living cells. Interestingly, our strategy led to the isolation of bacteria with interesting inhibitory activity against methicillin-resistant S. aureus (MRSA) as well as against Gram-negative bacteria.

SUBMITTER: Ibrahimi M

PROVIDER: S-EPMC7168292 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria.

Ibrahimi Manar M Korichi Wassila W Hafidi Mohamed M Lemee Laurent L Ouhdouch Yedir Y Loqman Souad S

Antibiotics (Basel, Switzerland) 20200219 2

Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of the Moroccan Atlantic coast. Only 4 Actinobacteria isolates showing strong predation capability against native or multidrug-resistant Gram-positive or Gram-negative bacteria were identified among 142 isolated potentia ...[more]

PMID: 32092889

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Project description:Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable target for the continued development of broadly active antiviral compounds.

Dataset Information

Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria.

Publications

Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria.

Similar Datasets

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