Prediction of the intestinal resistome by a three-dimensional structure-based method

Ruppé, Étienne; Ghozlane, Amine; Tap, Julien; Pons, Nicolas; Alvarez, Anne‐Sophie; Maziers, Nicolas; Cuesta, Trinidad; Hernando-Amado, Sara; Clares, Irene; Martínez, José Luis; Coque, Teresa M.; Baquero, Fernando; Lanza, Val F.; Máiz, Luís; Goulenok, Tiphaine; Lastours, Victoire de; Amor, Nawal; Fantin, Bruno; Wieder, Ingrid; Andremont, Antoine; Schaik, Willem van; Rogers, Malbert R. C.; Zhang, Xinglin; Willems, Rob J. L.; Brevern, Alexandre G. de; Batto, Jean-Michel; Blottière, Hervé M.; Léonard, Pierre; Lejard, Véronique; Letur, Aline; Levenez, Florence; Weiszer, Kevin; Haimet, Florence; Doré, Joël; Kennedy, Sean; Ehrlich, S. Dusko

doi:10.1038/s41564-018-0292-6

Cited by 152 publications

(139 citation statements)

References 68 publications

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“…This has been further illustrated by the administration of an oral beta-lactamase, which was shown to reduce the fecal concentrations of ceftriaxone (24). This beta-lactamase activity of commensal bacteria might protect against the selection of resistant Gram-negative enteric bacillus populations (25,26).…”

Section: Discussionmentioning

confidence: 99%

Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens

Burdet

Grall

Linard

et al. 2019

Antimicrob Agents Chemother

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Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)

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Section: Discussionmentioning

confidence: 99%

Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens

Burdet

Grall

Linard

et al. 2019

Antimicrob Agents Chemother

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“…A mutation in a chromosomal gene might result in a resistance phenotype, but this mutated gene is rarely transferred to other bacterial species. In fact, the majority of the resistance genes detected in metagenomes are permanently associated with the same microorganisms (Fondi et al, 2016); i.e., they are intrinsic resistance genes (Olivares-Pacheco et al, 2013;Forsberg et al, 2014;Ruppé et al, 2019). However, most of antibiotic resistance genes of importance in public health are located into MGEs .…”

Section: Antibiotic Resistance Genes In the Mobile Accessory Genomementioning

confidence: 99%

Gene Transmission in the One Health Microbiosphere and the Channels of Antimicrobial Resistance

et al. 2019

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Antibiotic resistance is a field in which the concept of One Health can best be illustrated. One Health is based on the definition of communication spaces among diverse environments. Antibiotic resistance is encoded by genes, however, these genes are propagated in mobile genetic elements (MGEs), circulating among bacterial species and clones that are integrated into the multiple microbiotas of humans, animals, food, sewage, soil, and water environments, the One Health microbiosphere. The dynamics and evolution of antibiotic resistance depend on the communication networks linking all these ecological, biological, and genetic entities. These communications occur by environmental overlapping and merging, a critical issue in countries with poor sanitation, but also favored by the homogenizing power of globalization. The overwhelming increase in the population of highly uniform food animals has contributed to the parallel increase in the absolute size of their microbiotas, consequently enhancing the possibility of microbiome merging between humans and animals. Microbial communities coalescence might lead to shared microbiomes in which the spread of antibiotic resistance (of human, animal, or environmental origin) is facilitated. Intermicrobiome communication is exerted by shuttle bacterial species (or clones within species) belonging to generalist taxa, able to multiply in the microbiomes of various hosts, including humans, animals, and plants. Their integration into local genetic exchange communities fosters antibiotic resistance gene flow, following the channels of accessory genome exchange among bacterial species. These channels delineate a topology of gene circulation, including dense clusters of species with frequent historical and recent exchanges. The ecological compatibility of these species, sharing the same niches and environments, determines the exchange possibilities. In summary, the fertility of the One Health approach to antibiotic

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“…The intestine is considered a huge reservoir for antibiotic resistance determinants. The preponderance of determinants can, however, be considered inherent, and they are rarely shared with opportunistic pathogens (Ruppé et al, 2019). This is possibly due to the presence of unknown obstacles for this transfer from gut anaerobic eubionts (mainly Bacteroides) to Gram-negative facultative anaerobic pathobionts (e.g., Enterobacteriaceae) (van Schaik, 2015).…”

Section: Antimicrobial Resistance and The Rise Of Another -Ome: The Rmentioning

confidence: 99%

Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods

et al. 2020

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Prediction of the intestinal resistome by a three-dimensional structure-based method

Cited by 152 publications

References 68 publications

Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens

Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens

Gene Transmission in the One Health Microbiosphere and the Channels of Antimicrobial Resistance

Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods

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