scholarly journals Non-antibiotic pharmaceuticals can enhance the spread of antibiotic resistance via conjugation

2019 ◽  
Author(s):  
Yue Wang ◽  
Ji Lu ◽  
Shuai Zhang ◽  
Jie Li ◽  
Likai Mao ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Cell Membrane ◽  
Membrane Permeability ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Protein Sequencing ◽  
Cell Membrane Permeability ◽  
Lipid Lowering ◽  
Potential Contribution

AbstractAntibiotic resistance is a global threat for public health. It is widely acknowledged that antibiotics at sub-inhibitory concentrations are important in disseminating antibiotic resistance via horizontal gene transfer. While there is high use of non-antibiotic human-targeted pharmaceuticals in our societies, the potential contribution of these on the spread of antibiotic resistance has been overlooked so far. Here, we report that commonly consumed non-antibiotic pharmaceuticals, including nonsteroidal anti-inflammatories (ibuprofen, naproxen, diclofenac), a lipid-lowering drug (gemfibrozil), and a β-blocker (propanolol), at clinically and environmentally relevant concentrations, significantly accelerated the conjugation of plasmid-borne antibiotic resistance genes. We looked at the response to these drugs by the bacteria involved in the gene transfer through various analyses that included monitoring reactive oxygen species (ROS) and cell membrane permeability by flow cytometry, cell arrangement, and whole-genome RNA and protein sequencing. We found the enhanced conjugation correlated well with increased production of ROS and cell membrane permeability. We also detected closer cell-to-cell contact and upregulated conjugal genes. Additionally, these non-antibiotic pharmaceuticals caused the bacteria to have responses similar to those detected when exposed to antibiotics, such as inducing the SOS response, and enhancing efflux pumps. The findings advance our understanding of the bacterial transfer of antibiotic resistance genes, and importantly emphasize concerns of non-antibiotic human-targeted pharmaceuticals for enhancing the spread of antibiotic resistance.

scholarly journals Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer

2021 ◽  
Author(s):  
Zhigang Yu ◽  
Yue Wang ◽  
Ji Lu ◽  
Philip L. Bond ◽  
Jianhua Guo
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Cell Membrane ◽  
Membrane Permeability ◽  
Resistance Genes ◽  
Food Additives ◽  
Antibiotic Resistance Genes ◽  
Sos Response ◽  
Conjugative Plasmid ◽  
Cell Membrane Permeability

AbstractAntimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.

scholarly journals Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
María Getino ◽  
David J. Sanabria-Ríos ◽  
Raúl Fernández-López ◽  
Javier Campos-Gómez ◽  
José M. Sánchez-López ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Aliphatic Chain ◽  
Bacterial Conjugation ◽  
Human Pathogens

ABSTRACT Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.

scholarly journals Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susanne Schjørring ◽  
Karen A. Krogfelt
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Resistance Genes ◽  
Bacterial Flora ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Gi Tract ◽  
Antibiotic Resistant ◽  
Multiresistant Bacteria ◽  
Resistant Strains

We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut.

scholarly journals Herbicide selection promotes antibiotic resistance in soil microbiomes

2021 ◽  
Author(s):  
Hanpeng Liao ◽  
Xi Li ◽  
Qiue Yang ◽  
Yudan Bai ◽  
Peng Cui ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Agricultural Soils ◽  
Soil Microbial Communities ◽  
Antibiotic Resistance Genes ◽  
Cell Membrane Permeability ◽  
Herbicide Application ◽  
Soil Microbial ◽  
Resistance Plasmids ◽  
Selection For

Abstract Herbicides are one of the most widely used chemicals in agriculture. While they are known to be harmful to non-target organisms, the effects of herbicides on the composition and functioning of soil microbial communities remain unclear. Here we show that application of three widely used herbicides—glyphosate, glufosinate and dicamba—increase the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in soil microbiomes without clear changes in the abundance, diversity and composition of bacterial communities. Mechanistically, these results could be explained by a positive selection for more tolerant genotypes that acquired several mutations in previously well-characterized herbicide and antibiotic resistance genes. Moreover, herbicide exposure increased cell membrane permeability and conjugation frequency of multidrug resistance plasmids, promoting ARG movement between bacteria. A similar pattern was found in agricultural soils across eleven provinces in China, where herbicide application, and the levels of glyphosate residues in soils, were associated with increased ARG and MGE abundances relative to herbicide-free control sites. Together, our results show that herbicide application can enrich ARGs and MGEs by changing the genetic composition of soil microbiomes, potentially contributing to the global antimicrobial resistance problem in agricultural environments.

scholarly journals Horizontal gene transfer facilitates the spread of extracellular antibiotic resistance genes in soil

2021 ◽  
Author(s):  
Heather A. Kittredge ◽  
Kevin M. Dougherty ◽  
Sarah E. Evans
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Natural Transformation ◽  
Antibiotic Resistance Genes ◽  
Live Cells ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant

AbstractAntibiotic resistance genes (ARGs) are ubiquitous in the environment and pose a serious risk to human and veterinary health. While many studies focus on the spread of live antibiotic resistant bacteria throughout the environment, it is unclear whether extracellular ARGs from dead cells can transfer to live bacteria to facilitate the evolution of antibiotic resistance in nature. Here, we inoculate antibiotic-free soil with extracellular ARGs (eARGs) from dead Pseudeononas stutzeri cells and track the evolution of antibiotic resistance via natural transformation – a mechanism of horizontal gene transfer involving the genomic integration of eARGs. We find that transformation facilitates the rapid evolution of antibiotic resistance even when eARGs occur at low concentrations (0.25 μg g-1 soil). However, when eARGs are abundant, transformation increases substantially. The evolution of antibiotic resistance was high under soil moistures typical in terrestrial systems (5%-30% gravimetric water content) and was only inhibited at very high soil moistures (>30%). While eARGs transformed into live cells at a low frequency, exposure to a low dose of antibiotic allowed a small number of transformants to reach high abundances in laboratory populations, suggesting even rare transformation events pose a risk to human health. Overall, this work demonstrates that dead bacteria and their eARGs are an overlooked path to antibiotic resistance, and that disinfection alone is insufficient to stop the spread of antibiotic resistance. More generally, the spread of eARGs in antibiotic-free soil suggests that transformation allows genetic variants to establish at low frequencies in the absence of antibiotic selection.ImportanceOver the last decade, antibiotics in the environment have gained increasing attention because they can select for drug-resistant phenotypes that would have otherwise gone extinct. To counter this effect, bacterial populations exposed to antibiotics often undergo disinfection. However, the release of extracellular antibiotic resistance genes (eARGs) into the environment following disinfection can promote the transfer of eARGs through natural transformation. This phenomenon is well-documented in wastewater and drinking water, but yet to be investigated in soil. Our results directly demonstrate that eARGs from dead bacteria are an important, but often overlooked source of antibiotic resistance in soil. We conclude that disinfection alone is insufficient to prevent the spread of ARGs. Special caution should be taken in releasing antibiotics into the environment, even if there are no live antibiotic resistant bacteria in the community, as transformation allows DNA to maintain its biological activity past microbial death.

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