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

mBio ◽  
2022 ◽  
Author(s):  
Lingxian Yi ◽  
Romain Durand ◽  
Frédéric Grenier ◽  
Jun Yang ◽  
Kaiyang Yu ◽  
...  

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.

Author(s):  
Méril Massot ◽  
Pierre Châtre ◽  
Bénédicte Condamine ◽  
Véronique Métayer ◽  
Olivier Clermont ◽  
...  

Intestinal carriage of extended spectrum β-lactamase (ESBL)-producing Escherichia coli is a frequent, increasing and worrying phenomenon, but little is known about the molecular scenario and the evolutionary forces at play. We screened 45 veal calves, known to have high prevalence of carriage, for ESBL-producing E. coli on 514 rectal swabs (one randomly selected colony per sample) collected over six months. We characterized the bacterial clones and plasmids carrying bla ESBL genes with a combination of genotyping methods, whole genome sequencing and conjugation assays. One hundred and seventy-three ESBL-producing E. coli isolates [ bla CTX-M-1 (64.7%), bla CTX-M -14 (33.5%) or bla CTX-M-15 (1.8%)] were detected, belonging to 32 bacterial clones, mostly of phylogroup A. Calves were colonized successively by different clones with a trend in decreasing carriage. The persistence of a clone in a farm was significantly associated with the number of calves colonized. Despite a high diversity of E. coli clones and bla CTX-M -carrying plasmids, few bla CTX-M gene/plasmid/chromosomal background combinations dominated, due to (i) efficient colonization of bacterial clones and/or (ii) successful plasmid spread in various bacterial clones. The scenario ‘clone vs. plasmid spread’ depended on the farm. Thus, epistatic interactions between resistance genes, plasmids and bacterial clones contribute to optimize fitness in specific environments. Importance The gut microbiota is the epicenter of the emergence of resistance. Considerable amount of knowledge on the molecular mechanisms of resistance has been accumulated but the ecological and evolutionary forces at play in nature are less studied. In this context, we performed a field work on temporal intestinal carriage of extended spectrum β-lactamase (ESBL)-producing Escherichia coli in veal farms. Veal calves are animals with one of the highest levels of ESBL producing E. coli fecal carriage, due to early high antibiotic exposure. We were able to show that calves were colonized successively by different ESBL-producing E. coli clones, and that two main scenarios were at play in the spread of bla CTX-M genes among calves: efficient colonization of several calves by a few bacterial clones and successful plasmid spread in various bacterial clones. Such knowledge should help develop new strategies to fight the emergence of antibiotic-resistance.


2006 ◽  
Vol 2 (3) ◽  
pp. 463-465 ◽  
Author(s):  
C.M Yates ◽  
D.J Shaw ◽  
A.J Roe ◽  
M.E.J Woolhouse ◽  
S.G.B Amyes

The study of antibiotic resistance has in the past focused on organisms that are pathogenic to humans or animals. However, the development of resistance in commensal organisms is of concern because of possible transfer of resistance genes to zoonotic pathogens. Conjugative plasmids are genetic elements capable of such transfer and are traditionally thought to engender a fitness burden on host bacteria. In this study, conjugative apramycin resistance plasmids isolated from newborn calves were characterized. Calves were raised on a farm that had not used apramycin or related aminoglycoside antibiotics for at least 20 months prior to sampling. Of three apramycin resistance plasmids, one was capable of transfer at very high rates and two were found to confer fitness advantages on new Escherichia coli hosts. This is the first identification of natural plasmids isolated from commensal organisms that are able to confer a fitness advantage on a new host. This work indicates that reservoirs of antibiotic resistance genes in commensal organisms might not decrease if antibiotic usage is halted.


2019 ◽  
Vol 16 (5) ◽  
pp. 347 ◽  
Author(s):  
Xiaolin Lai ◽  
Pingxiao Wu ◽  
Bo Ruan ◽  
Juan Liu ◽  
Zehua Liu ◽  
...  

Environmental contextAntibiotic resistance by microorganisms in the natural environment poses a threat to ecosystems and public health. We report findings suggesting kaolinite can effectively inhibit the development of antibiotic resistance genes in microorganisms, and present a new understanding of the molecular mechanisms that promote the development of antibiotic resistance. These results are critical to mitigating environmental and public health risks resulting from the abuse of antibiotics. AbstractAntibiotic resistance and antibiotic resistance genes (ARGs) in the natural environment pose a threat to ecosystems and public health; therefore, better strategies are needed to mitigate the emergence of resistance. This study examined the expression of ARGs in Escherichia coli (E. coli) after exposure to sub-MIC (minimum inhibitory concentration) antibiotics for 15 days in the presence and absence of kaolinite. The results of the real-time polymerase chain reaction (PCR) showed that the expression levels of the eight target genes of E. coli adhering to kaolinite were relatively decreased, and the MIC results also indicated that the final resistance was lower than that of the strains without kaolinite. A close relationship between E. coli and kaolinite was also revealed, as well as a unique interfacial interaction. In addition, the differential protein expression was further analysed to detect proteins and genes associated with ARGs mutations, and then the underlying mechanisms of cell growth and metabolism were identified under low dose ampicillin stress to elucidate the role of kaolinite in the process. Molecular mechanisms analysis determined that when cells adhering to kaolinite were stressed, transport of ampicillin to the periplasmic space was reduced, and the redox metabolism of bacteria was promoted to combat the harsh environment. Moreover, cells synthesised related peptides or proteins under the action of ribosomal proteins to prevent toxic damage. Therefore, this work not only provides new insights into the cellular response to antibiotic stress, but also provides a topic for more research on methods to delay the emergence of ARGs.


2004 ◽  
Vol 48 (10) ◽  
pp. 3996-4001 ◽  
Author(s):  
Yolanda Sáenz ◽  
Laura Briñas ◽  
Elena Domínguez ◽  
Joaquim Ruiz ◽  
Myriam Zarazaga ◽  
...  

ABSTRACT Seventeen multiple-antibiotic-resistant nonpathogenic Escherichia coli strains of human, animal, and food origins showed a wide variety of antibiotic resistance genes, many of them carried by class 1 and class 2 integrons. Amino acid changes in MarR and mutations in marO were identified for 15 and 14 E. coli strains, respectively.


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