Reversing Antibiotic Resistance Caused by Mobile Resistance Genes of High Fitness Cost

ABSTRACTThe treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (blaCTX-M-14), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of theblaCTX-M-14gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.

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A Locked Nucleic Acid (LNA)-Based Real-Time PCR Assay for the Rapid Detection of Multiple Bacterial Antibiotic Resistance Genes Directly from Positive Blood Culture

PLoS ONE ◽

10.1371/journal.pone.0120464 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120464 ◽

Cited By ~ 3

Author(s):

Lingxiang Zhu ◽

Dingxia Shen ◽

Qiming Zhou ◽

Zexia Li ◽

Xiangdong Fang ◽

...

Keyword(s):

Antibiotic Resistance ◽

Nucleic Acid ◽

Blood Culture ◽

Resistance Genes ◽

Positive Blood Culture ◽

Rapid Detection ◽

Antibiotic Resistance Genes ◽

Locked Nucleic Acid ◽

Pcr Assay ◽

Bacterial Antibiotic Resistance

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The requirements at the C-3 position of alkylquinolones for signalling in Pseudomonas aeruginosa

Organic & Biomolecular Chemistry ◽

10.1039/c6ob01930g ◽

2017 ◽

Vol 15 (2) ◽

pp. 306-310 ◽

Cited By ~ 12

Author(s):

Rachel Shanahan ◽

F. Jerry Reen ◽

Rafael Cano ◽

Fergal O'Gara ◽

Gerard P. McGlacken

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Bacterial Infections ◽

Innovative Strategies ◽

Bacterial Antibiotic Resistance ◽

New Antibiotics ◽

Perfect Storm

The ‘perfect storm’ of increasing bacterial antibiotic resistance and a decline in the discovery of new antibiotics, has made it necessary to search for new and innovative strategies to treat bacterial infections.

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PixR, a Novel Activator of Conjugative Transfer of IncX4 Resistance Plasmids, Mitigates the Fitness Cost of mcr-1 Carriage in Escherichia coli

mBio ◽

10.1128/mbio.03209-21 ◽

2022 ◽

Author(s):

Lingxian Yi ◽

Romain Durand ◽

Frédéric Grenier ◽

Jun Yang ◽

Kaiyang Yu ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Molecular Mechanisms ◽

Antibiotic Resistance Genes ◽

Fitness Cost ◽

Conjugative Transfer ◽

Resistance Plasmids

The spread of clinically relevant antibiotic resistance genes is often linked to the dissemination of epidemic plasmids. However, the underlying molecular mechanisms contributing to the successful spread of epidemic plasmids remain unclear.

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The impacts of different high-throughput profiling approaches on the understanding of bacterial antibiotic resistance genes in a freshwater reservoir

The Science of The Total Environment ◽

10.1016/j.scitotenv.2019.133585 ◽

2019 ◽

Vol 693 ◽

pp. 133585 ◽

Cited By ~ 4

Author(s):

Xuan Liu ◽

Peng Xiao ◽

Yunyan Guo ◽

Lemian Liu ◽

Jun Yang

Keyword(s):

Antibiotic Resistance ◽

High Throughput ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Bacterial Antibiotic Resistance ◽

Freshwater Reservoir

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Mobile Compensatory Mutations Promote Plasmid Survival

mSystems ◽

10.1128/msystems.00186-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 10

Author(s):

Martin Zwanzig ◽

Ellie Harrison ◽

Michael A. Brockhurst ◽

James P. J. Hall ◽

Thomas U. Berendonk ◽

...

Keyword(s):

Antibiotic Resistance ◽

Human Health ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Host Cells ◽

Compensatory Mutation ◽

Compensatory Evolution ◽

Resistance Plasmids ◽

Compensatory Mutations ◽

Chromosomal Mutations

ABSTRACTThe global dissemination of plasmids encoding antibiotic resistance represents an urgent issue for human health and society. While the fitness costs for host cells associated with plasmid acquisition are expected to limit plasmid dissemination in the absence of positive selection of plasmid traits, compensatory evolution can reduce this burden. Experimental data suggest that compensatory mutations can be located on either the chromosome or the plasmid, and these are likely to have contrasting effects on plasmid dynamics. Whereas chromosomal mutations are inherited vertically through bacterial fission, plasmid mutations can be inherited both vertically and horizontally and potentially reduce the initial cost of the plasmid in new host cells. Here we show using mathematical models and simulations that the dynamics of plasmids depends critically on the genomic location of the compensatory mutation. We demonstrate that plasmid-located compensatory evolution is better at enhancing plasmid persistence, even when its effects are smaller than those provided by chromosomal compensation. Moreover, either type of compensatory evolution facilitates the survival of resistance plasmids at low drug concentrations. These insights contribute to an improved understanding of the conditions and mechanisms driving the spread and the evolution of antibiotic resistance plasmids.IMPORTANCEUnderstanding the evolutionary forces that maintain antibiotic resistance genes in a population, especially when antibiotics are not used, is an important problem for human health and society. The most common platform for the dissemination of antibiotic resistance genes is conjugative plasmids. Experimental studies showed that mutations located on the plasmid or the bacterial chromosome can reduce the costs plasmids impose on their hosts, resulting in antibiotic resistance plasmids being maintained even in the absence of antibiotics. While chromosomal mutations are only vertically inherited by the daughter cells, plasmid mutations are also provided to bacteria that acquire the plasmid through conjugation. Here we demonstrate how the mode of inheritance of a compensatory mutation crucially influences the ability of plasmids to spread and persist in a bacterial population.

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High concentration and high dose of disinfectants and antibiotics used during the COVID-19 pandemic threaten human health

Environmental Sciences Europe ◽

10.1186/s12302-021-00456-4 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Zhongli Chen ◽

Jinsong Guo ◽

Yanxue Jiang ◽

Ying Shao

Keyword(s):

Antibiotic Resistance ◽

Human Health ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Gene Transformation ◽

Resistant Bacteria ◽

High Dose ◽

High Concentration ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant

AbstractThe issue of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created enormous threat to global health. In an effort to contain the spread of COVID-19, a huge amount of disinfectants and antibiotics have been utilized on public health. Accordingly, the concentration of disinfectants and antibiotics is increasing rapidly in various environments, including wastewater, surface waters, soils and sediments. The aims of this study were to analyze the potential ecological environment impacts of disinfectants and antibiotics by summarizing their utilization, environmental occurrence, distribution and toxicity. The paper highlights the promoting effects of disinfectants and antibiotics on antibiotic resistance genes (ARGs) and even antibiotic resistant bacteria (ARB). The scientific evidences indicate that the high concentration and high dose of disinfectants and antibiotics promote the evolution toward antimicrobial resistance through horizontal gene transformation and vertical gene transformation, which threaten human health. Further concerns should be focused more on the enrichment, bioaccumulation and biomagnification of disinfectants, antibiotics, antibiotic resistance genes (ARGs) and even antibiotic resistant bacteria (ARB) in human bodies.

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