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 ◽  
...  

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.

2021 ◽  
Author(s):  
Heather A. Kittredge ◽  
Kevin M. Dougherty ◽  
Sarah E. Evans

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gerardo Carranza ◽  
Tamara Menguiano ◽  
Fernando Valenzuela-Gómez ◽  
Yolanda García-Cazorla ◽  
Elena Cabezón ◽  
...  

Bacterial conjugation is the main mechanism for horizontal gene transfer, conferring plasticity to the genome repertoire. This process is also the major instrument for the dissemination of antibiotic resistance genes. Hence, gathering primary information of the mechanism underlying this genetic transaction is of a capital interest. By using fluorescent protein fusions to the ATPases that power conjugation, we have been able to track the localization of these proteins in the presence and absence of recipient cells. Moreover, we have found that more than one copy of the conjugative plasmid is transferred during mating. Altogether, these findings provide new insights into the mechanism of such an important gene transfer device.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susanne Schjørring ◽  
Karen A. Krogfelt

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.


Water ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1897 ◽  
Author(s):  
Amarachukwu Obayiuwana ◽  
Abasiofiok M. Ibekwe

The proliferation of antibiotic-resistant bacteria (ARB) and the prevalence of antibiotic resistance genes (ARGs) in wastewaters are well-established factors that contribute to the reduced potency of antibiotics used in healthcare worldwide. The human health risk associated with the proliferation of ARB and ARGs need to be understood in order to design mitigation measures to combat their dissemination. Using the PCR analysis of genomic DNA, the prevalence of 41 ARGs active against the commonly used six classes of antibiotics was evaluated in 60 bacterial isolates obtained from pharmaceutical wastewaters in Nigeria. The ARGs most frequently detected from the bacterial isolates in each of the antibiotic classes under study include catA1 (58.3%); sulI (31.7%); tet(E) (30%); aac(3)-IV (28.3%); ermC (20%); blaTEM, blaCTX-M, blaNDM-1 at 18.3% each; which encode for resistance to chloramphenicol, sulfonamides, tetracycline, aminoglycoside, macrolide-lincosamide-streptogramin and β-lactams and penicillins, respectively. Acinetobacter spp., accession number MH396735 expressed the highest number of ARGs of all the bacterial isolates, having at least one gene that encodes for resistance to all the classes of antibiotics in the study. This study highlights wide distribution of ARB and ARGs to the antibiotics tested in the wastewater, making pharmaceutical wastewater reservoirs of ARGs which could potentially be transferred from commensal microorganisms to human pathogens.


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