scholarly journals Mobilization of antibiotic resistance genes differ by resistance mechanism

2021 ◽  
Author(s):  
Tue Kjærgaard Nielsen ◽  
Patrick Denis Browne ◽  
Lars Hestbjerg Hansen
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Strong Association ◽  
Resistance Mechanism ◽  
Antibiotic Resistance Genes ◽  
Housekeeping Genes ◽  
Is Elements ◽  
Resistance Determinants ◽  
Phylogenetic Dispersion ◽  
Antibiotic Efflux

AbstractThe degree to which antibiotic resistance genes (ARGs) are mobilized by insertion sequence (IS) elements, plasmids, and integrons has a strong association with their likelihood to function as resistance determinants. This stems from genetic decontextualization where strong promoters often present in IS elements and integrons and the copy number effect of plasmids contribute to high expression of accessory genes. Here, we screen all complete bacterial RefSeq genomes for ARGs. The genetic contexts of detected ARGs are investigated for IS elements, integrons, plasmids, and phylogenetic dispersion. The ARG-MOB scale is proposed which indicates how mobilized detected ARGs are in bacterial genomes. Antibiotic efflux genes are rarely mobilized and it is concluded that these are often housekeeping genes that are not decontextualized to confer resistance through overexpression. Even 80% of β-lactamases have never, or very rarely, been mobilized in the 15,790 studied genomes. However, some ARGs are indeed mobilized and co-occur with IS elements, plasmids, and integrons. These results have consequences for the design and interpretation of studies screening for resistance determinants, as mobilized ARGs pose a more concrete risk to human health, especially under heterologous expression, than groups of ARGs that have only been shown to confer resistance in cloning experiments.

scholarly journals Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 378
Author(s):  
Inka Marie Willms ◽  
Maja Grote ◽  
Melissa Kocatürk ◽  
Lukas Singhoff ◽  
Alina Andrea Kraft ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Reference Database ◽  
Functional Metagenomics ◽  
Beta Lactam ◽  
Public Attention ◽  
Soil Ecosystems ◽  
High Level ◽  
Antibiotic Efflux

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

scholarly journals The Influencing Factors of Bacterial Resistance Related to Livestock Farm: Sources and Mechanisms

2021 ◽  
Vol 2 ◽  
Author(s):  
Kaixuan Guo ◽  
Yue Zhao ◽  
Luqing Cui ◽  
Zhengzheng Cao ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Influencing Factors ◽  
Resistance Genes ◽  
Bacterial Resistance ◽  
Genetic Material ◽  
Resistance Mechanism ◽  
Antibiotic Resistance Genes ◽  
Direct Selection ◽  
Adaptive Mutation ◽  
Specific Response

Bacterial resistance is a complex scientific issue. To manage this issue, we need to deeply understand the influencing factors and mechanisms. Based on the background of livestock husbandry, this paper reviews the factors that affect the acquisition of bacterial resistance. Meanwhile, the resistance mechanism is also discussed. “Survival of the fittest” is the result of genetic plasticity of bacterial pathogens, which brings about specific response, such as producing adaptive mutation, gaining genetic material or changing gene expression. To a large extent, bacterial populations acquire resistance genes directly caused by the selective pressure of antibiotics. However, mobile resistance genes may be co-selected by other existing substances (such as heavy metals and biocides) without direct selection pressure from antibiotics. This is because the same mobile genetic elements as antibiotic resistance genes can be co-located by the resistance determinants of some of these compounds. Furthermore, environmental factors are a source of resistance gene acquisition. Here, we describe some of the key measures that should be taken to mitigate the risk of antibiotic resistance. We call on the relevant governments or organizations around the world to formulate and improve the monitoring policies of antibiotic resistance, strengthen the supervision, strengthen the international cooperation and exchange, and curb the emergence and spread of drug-resistant strains.

scholarly journals Incidence, Distribution, and Spread of Tetracycline Resistance Determinants and Integron-Associated Antibiotic Resistance Genes among Motile Aeromonads from a Fish Farming Environment

2001 ◽  
Vol 67 (12) ◽  
pp. 5675-5682 ◽  
Author(s):  
Anja S. Schmidt ◽  
Morten S. Bruun ◽  
Inger Dalsgaard ◽  
Jens L. Larsen
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Tetracycline Resistance ◽  
Class 1 Integron ◽  
Gene Cassettes ◽  
Class 1 Integrons ◽  
Resistance Determinants ◽  
Class 1

ABSTRACT A collection of 313 motile aeromonads isolated at Danish rainbow trout farms was analyzed to identify some of the genes involved in high levels of antimicrobial resistance found in a previous field trial (A. S. Schmidt, M. S. Bruun, I. Dalsgaard, K. Pedersen, and J. L. Larsen, Appl. Environ. Microbiol. 66:4908–4915, 2000), the predominant resistance phenotype (37%) being a combined oxytetracycline (OTC) and sulphadiazine/trimethoprim resistance. Combined sulphonamide/trimethoprim resistance (135 isolates) appeared closely related to the presence of a class 1 integron (141 strains). Among the isolates containing integrons, four different combinations of integrated resistance gene cassettes occurred, in all cases including a dihydrofolate reductase gene and a downstream aminoglycoside resistance insert (87 isolates) and occasionally an additional chloramphenicol resistance gene cassette (31 isolates). In addition, 23 isolates had “empty” integrons without inserted gene cassettes. As far as OTC resistance was concerned, only 66 (30%) out of 216 resistant aeromonads could be assigned to resistance determinant class A (19 isolates), D (n = 6), or E (n = 39); three isolates contained two tetracycline resistance determinants (AD, AE, and DE). Forty OTC-resistant isolates containing large plasmids were selected as donors in a conjugation assay, 27 of which also contained a class 1 integron. Out of 17 successful R-plasmid transfers to Escherichia coli recipients, the respective integrons were cotransferred along with the tetracycline resistance determinants in 15 matings. Transconjugants were predominantly tetApositive (10 of 17) and contained class 1 integrons with two or more inserted antibiotic resistance genes. While there appeared to be a positive correlation between conjugative R-plasmids andtetA among the OTC-resistant aeromonads, tetEand the unclassified OTC resistance genes as well as class 1 integrons were equally distributed among isolates with and without plasmids. These findings indicate the implication of other mechanisms of gene transfer besides plasmid transfer in the dissemination of antibiotic resistance among environmental motile aeromonads.

scholarly journals Complete Nucleotide Sequence of Two Multidrug-Resistant IncR Plasmids from Klebsiella pneumoniae

2014 ◽  
Vol 58 (7) ◽  
pp. 4207-4210 ◽  
Author(s):  
Fabrice Compain ◽  
Lionel Frangeul ◽  
Laurence Drieux ◽  
Charlotte Verdet ◽  
Sylvain Brisse ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Nucleotide Sequence ◽  
Resistance Genes ◽  
Complete Nucleotide Sequence ◽  
Clinical Importance ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistance Determinants ◽  
Gene Carriers

ABSTRACTWe report here the complete nucleotide sequence of two IncR replicons encoding multidrug resistance determinants, including β-lactam (blaDHA-1,blaSHV-12), aminoglycoside (aphA1,strA,strB), and fluoroquinolone (qnrB4,aac6′-1b-cr) resistance genes. The plasmids have backbones that are similar to each other, including the replication and stability systems, and contain a wide variety of transposable elements carrying known antibiotic resistance genes. This study confirms the increasing clinical importance of IncR replicons as resistance gene carriers.

scholarly journals Conjugative delivery of CRISPR-Cas9 for the selective depletion of antibiotic-resistant enterococci

2019 ◽  
Author(s):  
Marinelle Rodrigues ◽  
Sara W. McBride ◽  
Karthik Hullahalli ◽  
Kelli L. Palmer ◽  
Breck A. Duerkop
Keyword(s):  
Antibiotic Resistance ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Conjugative Plasmid ◽  
Antibiotic Resistant ◽  
Resistance Determinants

AbstractThe innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiontEnterococcus faecalisis associated with HAIs and some strains are MDR. Therefore, novel strategies to controlE. faecalispopulations are needed. We previously characterized anE. faecalisType II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers toE. faecalisfor the selective removal of antibiotic resistance genes. Usingin vitrocompetition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistantE. faecalisby several orders of magnitude. Finally, we show thatE. faecalisdonor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinantsin vivo. Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.ImportanceCRISPR-Cas nucleic acid targeting systems hold promise for the amelioration of multidrug-resistant enterococci, yet the utility of such tools in the context of the intestinal environment where enterococci reside is understudied. We describe the development of a CRISPR-Cas antimicrobial, deployed on a conjugative plasmid, for the targeted removal of antibiotic resistance genes from intestinalEnterococcus faecalis. We demonstrate that CRISPR-Cas targeting reduces antibiotic resistance ofE. faecalisby several orders of magnitude in the intestine. Although barriers exist that influence the penetrance of the conjugative CRISPR-Cas antimicrobial among target recipientE. faecaliscells, the removal of antibiotic resistance genes inE. faecalisupon uptake of the CRISPR-Cas antimicrobial is absolute. In addition, cells that obtain the CRISPR-Cas antimicrobial are immunized against the acquisition of new antibiotic resistance genes. This study suggests a potential path toward plasmid based CRISPR-Cas therapies in the intestine.

scholarly journals Identification of Selected Antibiotic Resistance Genes in Two Different Wastewater Treatment Plant Systems in Poland: A Preliminary Study

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2851 ◽  
Author(s):  
Magdalena Pazda ◽  
Magda Rybicka ◽  
Stefan Stolte ◽  
Krzysztof Piotr Bielawski ◽  
Piotr Stepnowski ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Wastewater Treatment ◽  
Resistance Genes ◽  
Wastewater Treatment Plants ◽  
Treatment Plant ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Clear Trend ◽  
Resistance Determinants ◽  
Final Effluent

Antibiotic resistance is a growing problem worldwide. The emergence and rapid spread of antibiotic resistance determinants have led to an increasing concern about the potential environmental and public health endangering. Wastewater treatment plants (WWTPs) play an important role in this phenomenon since antibacterial drugs introduced into wastewater can exert a selection pressure on antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Therefore, WWTPs are perceived as the main sources of antibiotics, ARB and ARG spread in various environmental components. Furthermore, technological processes used in WWTPs and its exploitation conditions may influence the effectiveness of antibiotic resistance determinants’ elimination. The main aim of the present study was to compare the occurrence of selected tetracycline and sulfonamide resistance genes in raw influent and final effluent samples from two WWTPs different in terms of size and applied biological wastewater treatment processes (conventional activated sludge (AS)-based and combining a conventional AS-based method with constructed wetlands (CWs)). All 13 selected ARGs were detected in raw influent and final effluent samples from both WWTPs. Significant ARG enrichment, especially for tet(B, K, L, O) and sulIII genes, was observed in conventional WWTP. The obtained data did not show a clear trend in seasonal fluctuations in the abundance of selected resistance genes in wastewaters.

scholarly journals HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance

2018 ◽  
Vol 115 (52) ◽  
pp. 13359-13364 ◽  
Author(s):  
Mélodie Duval ◽  
Daniel Dar ◽  
Filipe Carvalho ◽  
Eduardo P. C. Rocha ◽  
Rotem Sorek ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Gene ◽  
Resistance Mechanism ◽  
Antibiotic Resistance Genes ◽  
Amino Acid Peptide ◽  
Splitting Factor ◽  
A Genome ◽  
Attenuation Mechanism ◽  
Drug Modification

To overcome the action of antibiotics, bacteria have evolved a variety of different strategies, such as drug modification, target mutation, and efflux pumps. Recently, we performed a genome-wide analysis ofListeria monocytogenesgene expression after growth in the presence of antibiotics, identifying genes that are up-regulated upon antibiotic treatment. One of them,lmo0762, is a homolog ofhflX, which encodes a heat shock protein that rescues stalled ribosomes by separating their two subunits. To our knowledge, ribosome splitting has never been described as an antibiotic resistance mechanism. We thus investigated the role oflmo0762in antibiotic resistance. First, we demonstrated thatlmo0762is an antibiotic resistance gene that confers protection against lincomycin and erythromycin, and that we renamedhflXr(hflXresistance). We show thathflXrexpression is regulated by a transcription attenuation mechanism relying on the presence of alternative RNA structures and a small ORF encoding a 14 amino acid peptide containing the RLR motif, characteristic of macrolide resistance genes. We also provide evidence that HflXr is involved in ribosome recycling in presence of antibiotics. Interestingly,L. monocytogenespossesses another copy ofhflX,lmo1296, that is not involved in antibiotic resistance. Phylogenetic analysis shows several events ofhflXrduplication in prokaryotes and widespread presence ofhflXrin Firmicutes. Overall, this study reveals theListeria hflXras the founding member of a family of antibiotic resistance genes. The resistance conferred by this gene is probably of importance in the environment and within microbial communities.

scholarly journals Occurrence and distribution of antibiotic resistance genes in lakes and reservoirs from water-receiving area of Eastern Route of the South-to-North Water Diversion Project, Northern China

2020 ◽  
Vol 20 (8) ◽  
pp. 3029-3037
Author(s):  
Wei Hou ◽  
Fang Hu ◽  
Shaohua Sun ◽  
Xiaotong Dong ◽  
Mingquan Wang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Local Level ◽  
Resistance Mechanism ◽  
Antibiotic Resistance Genes ◽  
Northern China ◽  
Water Diversion ◽  
Contamination Level ◽  
North Water ◽  
Study Sites

Abstract To characterize antibiotic resistance genes (ARGs) in surface waterbodies in Shandong Province, and to understand the occurrence, diversity and resistance mechanism of ARGs, nine aquatic ecosystems were selected and evaluated regarding occurrence of ARGs in the period from 2018 to 2019. Thirty-three types and 242 subtypes of ARGs were detected in the nine waterbodies with the most subtypes in Wohushan (242) and Jihongtan (235), and the fewest ARGs in Datun (213) and Mishan (221). Among the top nine ARG types, MacB, BcrA, CarA and TetW were the dominant ARGs in these samples. Four groups of the study sites were distinguished by cluster analysis, indicating different distribution characteristics of ARGs in these waterbodies, and regional differences in ARG contamination. Efflux pumps were the predominant resistance mechanism in all the waterbodies in terms of both subtype number (49.2%) and abundance (70.4%), followed by operon, antibiotic inactivation and others. Our findings provide comprehensive information to better understand the contamination level of ARGs on a local level as well as for global considerations, and may be practically helpful for the prevention and control of ARG pollution.

scholarly journals Screening and Quantification of the Expression of Antibiotic Resistance Genes in Acinetobacter baumannii with a Microarray

2009 ◽  
Vol 54 (1) ◽  
pp. 333-340 ◽  
Author(s):  
Sébastien Coyne ◽  
Ghislaine Guigon ◽  
Patrice Courvalin ◽  
Bruno Périchon
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Antibiotic Resistance Genes ◽  
Efflux Pumps ◽  
Single Step ◽  
Resistance Determinants

ABSTRACT An oligonucleotide-based DNA microarray was developed to evaluate expression of genes for efflux pumps in Acinetobacter baumannii and to detect acquired antibiotic resistance determinants. The microarray contained probes for 205 genes, including those for 47 efflux systems, 55 resistance determinants, and 35 housekeeping genes. The microarray was validated by comparative analysis of mutants overexpressing or deficient in the pumps relative to the parental strain. The performance of the microarray was also evaluated using in vitro single-step mutants obtained on various antibiotics. Overexpression, confirmed by quantitative reverse transcriptase PCR, of RND efflux pumps AdeABC, due to a G30D substitution in AdeS in a multidrug-resistant (MDR) strain obtained on gentamicin, and AdeIJK, in two mutants obtained on cefotaxime or tetracycline, was detected. A new efflux pump, AdeFGH, was found to be overexpressed in a mutant obtained on chloramphenicol. Study of MDR clinical isolates, including the AYE strain, whose entire sequence has been determined, indicated overexpression of AdeABC and of the chromosomally encoded cephalosporinase as well as the presence of several acquired resistance genes. The overexpressed and acquired determinants detected by the microarray could account for nearly the entire MDR phenotype of the isolates. The microarray is potentially useful for detection of resistance in A. baumannii and should allow detection of new efflux systems associated with antibiotic resistance.

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