Dissemination of antibiotic resistance genes from antibiotic producers to pathogens

Jiang, Xinglin; Ellabaan, Mostafa Mostafa Hashim; Charusanti, Pep; Munck, Christian; Blin, Kai; Tong, Yaojun; Weber, Tilmann; Sommer, Morten Otto Alexander; Lee, Sang Yup

doi:10.1038/ncomms15784

Cited by 299 publications

(179 citation statements)

References 40 publications

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“…ARGs can be acquired from any source and transferred between bacteria corresponding to different phyla [116]. Their dissemination is usually associated with mobile genetic elements.…”

Section: Antibiotic Resistance In the Environmentmentioning

confidence: 99%

Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

et al. 2020

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Staphylococcus aureus is an opportunist pathogen that is responsible for numerous types of infections. S. aureus is known for its ability to easily acquire antibiotic resistance determinants. Methicillin-resistant S. aureus (MRSA) is a leading cause of infections both in humans and animals and is usually associated with a multidrug-resistant profile. MRSA dissemination is increasing due to its capability of establishing new reservoirs and has been found in humans, animals and the environment. Despite the fact that the information on the incidence of MRSA in the environment and, in particular, in wild animals, is scarce, some studies have reported the presence of these strains among wildlife with no direct contact with antibiotics. This shows a possible transmission between species and, consequently, a public health concern. The aim of this review is to better understand the distribution, prevalence and molecular lineages of MRSA in European free-living animals.

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“…ARGs can be acquired from any source and transferred between bacteria corresponding to different phyla [116]. Their dissemination is usually associated with mobile genetic elements.…”

Section: Antibiotic Resistance In the Environmentmentioning

confidence: 99%

Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

et al. 2020

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“…The spread of antibiotic resistance genes (ARGs) (Martinez, 2008;Feng et al, 2018) in an environment is intensifying the risk of public exposure to multidrugresistant pathogens (Sommer et al, 2009;Jones-Dias et al, 2016;Jiang et al, 2017). The Chinese population harbours a huge abundance of ARGs (Feng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Rapidly mitigating antibiotic resistant risks in chicken manure by Hermetia illucens bioconversion with intestinal microflora

Cai

et al. 2018

Environmental Microbiology

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Summary Antibiotic resistance genes (ARGs) in animal manure are an environmental concern due to naturally occurring bacteria being exposed to these wastes and developing multidrug resistance. The bioconversion of manure with fly larvae is a promising alternative for recycling these wastes while attenuating ARGs. We investigated the impact of black soldier fly (BSF, Hermetia illucens) larval bioconversion of chicken manure on the persistence of associated ARGs. Compared with traditional composting or sterile larval treatments (by 48.4% or 88.7%), non‐sterile BSF larval treatments effectively reduced ARGs and integrin genes by 95.0% during 12 days, due to rapid decreases in concentrations of the genes and associated bacteria as they passed through the larval gut and were affected by intestinal microbes. After larval treatments, bacterial community composition differed significantly, with the percentage of Firmicutes possibly carrying ARGs reduced by 65.5% or more. On average, human pathogenic bacteria populations declined by 70.7%–92.9%, effectively mitigating risks of these bacteria carrying ARGs. Environmental pH, nitrogen content and antibiotic concentrations were closely related to both bacterial community composition and targeted gene attenuation in larval systems. Selective pressures of larval gut environments with intestinal microbes, larval bacteriostasis and reformulation of manure due to larval digestion contributed to ARG attenuation.

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“…Spontaneous mutations can create specific, hydrolytic enzymes that can either directly hydrolyze antibiotics or indirectly modify antibiotic targets (8)(9)(10). Compared with spontaneous mutation, horizontal gene transfer is the more dangerous mechanism because it can transfer antibiotic resistance between microbes at a fast rate (11)(12)(13). At present, nearly 50 countries and regions have confirmed the existence of MCR-1, including China, the United States, and Germany (2,(14)(15)(16)(17).…”

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confidence: 99%

Substrate analog interaction with MCR‐1 offers insight into the rising threat of the plasmid‐mediated transferable colistin resistance

et al. 2018

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Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

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Dissemination of antibiotic resistance genes from antibiotic producers to pathogens

Cited by 299 publications

References 40 publications

Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

Rapidly mitigating antibiotic resistant risks in chicken manure by Hermetia illucens bioconversion with intestinal microflora

Substrate analog interaction with MCR‐1 offers insight into the rising threat of the plasmid‐mediated transferable colistin resistance

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