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      Bioactivities and genome insights of a thermotolerant antibiotics‐producing Streptomyces sp. TM32 reveal its potentials for novel drug discovery

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          Abstract

          A way to defeat antimicrobial resistance (AMR) crisis is to supply novel drugs to the pharmaceutical industry. This effort leads to a global call for seeking the beneficial microbes from underexplored habitats. To support this call, we isolated Streptomyces sp. TM32 from the rhizosphere soil of a medicinal plant, turmeric ( Curcuma longa L.). TM32 exhibited strong antimicrobial activities against both human and plant pathogens, including an AMR pathogen, Staphylococcus haemolyticus MR‐CoNS. Surprisingly, such antimicrobial results of TM32's autoclaved crude extract remained the same. Based on the genome data analysis, TM32 belongs to the same genomic species with Streptomyces sioyaensis DSM 40032 T, supported by the relatively high‐average nucleotide identity values (ANIb: 96.80% and OrthoANIu: 97.14%) and in silico DNA–DNA relatedness value of 75.40%. Importantly, the gene annotation analyses revealed that TM32's genome contains various genes encoding the biosynthesis of either known or unknown antibiotics and some metabolites involved in plant growth‐promoting traits. However, bioactivities and genome data comparison of TM32 and DSM 40032 T showed a set of apparent differences, for example, antimicrobial potentials, genome size, number, and occurrence of coding DNA sequences in the chromosomes. These findings suggest that TM32 is a new strain of S. sioyaensis and serves as an emerging source for further discovery of valuable and novel bioactive compounds.

          Abstract

          Streptomyces sp. TM32 can produce thermotolerant antibiotics that inhibit growth of bacteria and fungi. There are many gene clusters in the genome of TM32, encoding unknown secondary metabolites and plant growth‐promoting traits. TM32 is a potential source for novel drug discovery.

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          Most cited references11

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          Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

          Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
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            Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river.

            Antibiotic resistance has become a major health concern; thus, there is a growing interest in exploring the occurrence of antibiotic resistance genes (ARGs) in the environment as well as the factors that contribute to their emergence. Aquatic ecosystems provide an ideal setting for the acquisition and spread of ARGs due to the continuous pollution by antimicrobial compounds derived from anthropogenic activities. We investigated, therefore, the pollution level of a broad range of antibiotics and ARGs released from hospital and urban wastewaters, their removal through a wastewater treatment plant (WWTP) and their presence in the receiving river. Several antimicrobial compounds were detected in all water samples collected. Among antibiotic families, fluoroquinolones were detected at the highest concentration, especially in hospital effluent samples. Although good removal efficiency by treatment processes was observed for several antimicrobial compounds, most antibiotics were still present in WWTP effluents. The results also revealed that copy numbers of ARGs, such as blaTEM (resistance to β-lactams), qnrS (reduced susceptibility to fluoroquinolones), ermB (resistance to macrolides), sulI (resistance to sulfonamides) and tetW (resistance to tetracyclines), were detected at the highest concentrations in hospital effluent and WWTP influent samples. Although there was a significant reduction in copy numbers of these ARGs in WWTP effluent samples, this reduction was not uniform across analyzed ARGs. Relative concentration of ermB and tetW genes decreased as a result of wastewater treatment, whereas increased in the case of blaTEM, sulI and qnrS genes. The incomplete removal of antibiotics and ARGs in WWTP severely affected the receiving river, where both types of emerging pollutants were found at higher concentration in downstream waters than in samples collected upstream from the discharge point. Taken together, our findings demonstrate a widespread occurrence of antibiotics and ARGs in urban and hospital wastewater and how these effluents, even after treatment, contribute to the spread of these emerging pollutants in the aquatic environment.
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              The crisis of no new antibiotics--what is the way forward?

              Antibiotic use not only underpins modern medicine, but has brought huge changes to the world, especially in expectations of survival of children into adulthood. The theme of World Health Day, 2011, was "antimicrobial resistance: no action today and no cure tomorrow". The demise of antibacterial drug discovery brings the spectre of untreatable infections. To prevent this crisis immediate action is needed and a new initiative, Antibiotic Action, has been launched. By bringing together communities who need these drugs with academia, health-care professionals, and pharmaceutical companies, this initiative aims to strengthen and enhance academic-industrial partnerships, bring about revision of costly and laborious processes of licensing and regulation of new antibiotics, and address the economics of antimicrobial drugs (cost of use vs profit). A global alliance for antibiotic drug discovery and development would provide a platform for these initiatives. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                rungroch.sungthong@glasgow.ac.uk
                Journal
                Microbiologyopen
                Microbiologyopen
                10.1002/(ISSN)2045-8827
                MBO3
                MicrobiologyOpen
                John Wiley and Sons Inc. (Hoboken )
                2045-8827
                02 April 2019
                November 2019
                : 8
                : 11 , ANTIMICROBIAL RESISTANCE ( doiID: 10.1002/mbo3.v8.11 )
                : e842
                Affiliations
                [ 1 ] Department of Microbiology and Parasitology, Faculty of Medical Science Naresuan University Phitsanulok 65000 Thailand
                [ 2 ] Microbiology Division, Department of Biology, Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand
                [ 3 ] Infrastructure and Environment Research Division, School of Engineering University of Glasgow Glasgow G12 8LT UK
                Author notes
                [*] [* ] Correspondence

                Rungroch Sungthong, Infrastructure and Environment Research Division, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.

                Email: rungroch.sungthong@ 123456glasgow.ac.uk

                Author information
                https://orcid.org/0000-0002-5052-2611
                Article
                MBO3842
                10.1002/mbo3.842
                6854843
                30941917
                354e5331-5184-435c-968b-a0bcbbd01aea
                © 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 February 2019
                : 13 March 2019
                : 14 March 2019
                Page count
                Figures: 0, Tables: 4, Pages: 7, Words: 4679
                Funding
                Funded by: Center of Excellence on Biodiversity – Office of Higher Education Commission
                Award ID: BDC-PG2-159010
                Funded by: Engineering and Physical Sciences Research Council , open-funder-registry 10.13039/501100000266;
                Award ID: EP/K038885/1
                Funded by: National Research Council of Thailand , open-funder-registry 10.13039/501100004704;
                Award ID: R2560B070
                Categories
                Special Issue: Antimicrobial Resistance
                Original Articles
                Custom metadata
                2.0
                November 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.2 mode:remove_FC converted:05.12.2019

                Microbiology & Virology
                antibiotics,antimicrobial resistance,bioactive compounds,genome mining,plant growth promotion,streptomyces

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