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Mangrove sediments are prone to anthropogenic activities that could enrich antibiotics resistance genes (ARGs). The emergence and dissemination of ARGs are of serious concern to public health worldwide. Therefore, a comprehensive resistome analysis of global mangrove sediment is of paramount importance. In this study, we have implemented a deep machine learning approach to analyze the resistome of mangrove sediments from Brazil, China, Saudi Arabia, India, and Malaysia. Geography (R ANOSIM  = 39.26%; p < 0.005) as well as human intervention (R ANOSIM  = 16.92%; p < 0.005) influenced the ARG diversity. ARG diversity was also inversely correlated to the human development index (HDI) of the host country (R = -0.53; p < 0.05) rather than antibiotics consumption (p > 0.05). Several genes including multidrug efflux pumps were significantly (p < 0.05) enriched in the sites with human intervention. Resistome was consistently dominated by rpoB2 (19.26 ± 0.01%), multidrug ABC transporter (10.40 ± 0.23%), macB (8.84 ± 0.36n%), tetA (4.13 ± 0.35%), mexF (3.26 ± 0.19%), CpxR (2.93 ± 0.2%), bcrA (2.38 ± 0.24%), acrB (2.37 ± 0.18%), mexW (2.19 ± 0.17%), and vanR (1.99 ± 0.11%). Besides, mobile ARGs such as vanA, tet(48), mcr, and tetX were also detected in the mangrove sediments. Comparative analysis against terrestrial and ocean resistomes showed that the ocean ecosystem harbored the lowest ARG diversity (Chao1 = 71.12) followed by mangroves (Chao1 = 258.07) and terrestrial ecosystem (Chao1 = 294.07). ARG subtypes such as abeS and qacG were detected exclusively in ocean datasets. Likewise, rpoB2, multidrug ABC transporter, and macB, detected in mangrove and terrestrial datasets, were not detected in the ocean datasets. This study shows that the socioeconomic factors strongly determine the antibiotic resistome in the mangrove. Direct anthropogenic intervention in the mangrove environment also enriches antibiotic resistome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Saline tolerant mangrove forests partake in vital biogeochemical cycles. However, they are endangered due to deforestation as a result of urbanization. In this study, we have carried out a metagenomic snapshot of the mangrove ecosystem from five countries to assess its taxonomic, functional and antibiotic resistome structure. Chao1 alpha diversity varied significantly (P < 0.001) between the countries (Brazil, Saudi Arabia, China, India and Malaysia). All datasets were composed of 33 phyla dominated by eight major phyla covering >90% relative abundance. Comparative analysis of mangrove with terrestrial and marine ecosystems revealed the strongest heterogeneity in the mangrove microbial community. We also observed that the mangrove community shared similarities to both the terrestrial and marine microbiome, forming a link between the two contrasting ecosystems. The antibiotic resistant genes (ARG) resistome was comprised of nineteen level 3 classifications dominated by multidrug resistance efflux pumps (46.7 ± 4.3%) and BlaR1 family regulatory sensor-transducer disambiguation (25.2 ± 4.8%). ARG relative abundance was significantly higher in Asian countries and in human intervention datasets at a global scale. Our study shows that the mangrove microbial community and its antibiotic resistance are affected by geography as well as human intervention and are unique to the mangrove ecosystem. Understanding changes in the mangrove microbiome and its ARG is significant for sustainable development and public health., (© FEMS 2020.)

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens., Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties., Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)