scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Acquired Antibiotic Resistance Genes: An Overview

TL;DR: Attention is paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.
Abstract: In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: A web server providing a convenient way of identifying acquired antimicrobial resistance genes in completely sequenced isolates was created, and the method was evaluated on WGS chromosomes and plasmids of 30 isolates.
Abstract: Objectives Identification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data.

3,956 citations

Journal ArticleDOI
TL;DR: A concise database for BLAST using a Bio-Edit interface that can detect AR genetic determinants in bacterial genomes and can rapidly and easily discover putative new AR geneticeterminants is created.
Abstract: ARG-ANNOT (Antibiotic Resistance Gene-ANNOTation) is a new bioinformatic tool that was created to detect existing and putative new antibiotic resistance (AR) genes in bacterial genomes. ARG-ANNOT uses a local BLAST program in Bio-Edit software that allows the user to analyze sequences without a Web interface. All AR genetic determinants were collected from published works and online resources; nucleotide and protein sequences were retrieved from the NCBI GenBank database. After building a database that includes 1,689 antibiotic resistance genes, the software was tested in a blind manner using 100 random sequences selected from the database to verify that the sensitivity and specificity were at 100% even when partial sequences were queried. Notably, BLAST analysis results obtained using the rmtF gene sequence (a new aminoglycoside-modifying enzyme gene sequence that is not included in the database) as a query revealed that the tool was able to link this sequence to short sequences (17 to 40 bp) found in other genes of the rmt family with significant E values. Finally, the analysis of 178 Acinetobacter baumannii and 20 Staphylococcus aureus genomes allowed the detection of a significantly higher number of AR genes than the Resfinder gene analyzer and 11 point mutations in target genes known to be associated with AR. The average time for the analysis of a genome was 3.35 ± 0.13 min. We have created a concise database for BLAST using a Bio-Edit interface that can detect AR genetic determinants in bacterial genomes and can rapidly and easily discover putative new AR genetic determinants.

1,016 citations


Cites background from "Acquired Antibiotic Resistance Gene..."

  • ...The sequence information for the AR genes was collected from different resources, and the information for 1,689 AR genes was included in the database (7, 9, 18, 20, 28)....

    [...]

Journal ArticleDOI
TL;DR: A revised understanding of microbial energy requirements will require identifying the factors that comprise true basal maintenance and the adaptations that might serve to minimize these factors.
Abstract: The discovery of abundant microbial life in the deep subsurface, where energy fluxes can be orders of magnitude lower than in laboratory cultures, challenges many of our assumptions about the requirements to sustain life. Here, Tori Hoehler and Bo Barker Jorgensen review our understanding of life in these extremely low-energy environments.

574 citations

Journal ArticleDOI
TL;DR: The metagenomic analysis showed that the activated sludge and the digested sludge exhibited different microbial communities and changes in the types and occurrence of ARGs and MGEs, and indicated that some environmental bacteria might be potential hosts of multiple ARGs.

537 citations


Cites background from "Acquired Antibiotic Resistance Gene..."

  • ...If an ARG is on 280 a conjugative or mobilizable plasmid, then this ARG has the potential to transfer among bacteria 281 (Bennett, 2008; van Hoek et al., 2011), so that resistance can spread throughout a given ecosystem....

    [...]

  • ...Conjugative transposons, like conjugative plasmids contain an origin of 275 transfer and the genes required to make the conjugation pparatus (van Hoek et al., 2011)....

    [...]

Journal ArticleDOI
TL;DR: A conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic is provided and the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates are explored.
Abstract: Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.

504 citations

References
More filters
Book
01 Mar 1989
TL;DR: This updated and expanded edition now offers 297 chapters that cover the basic principles of diagnosis and management, major clinical syndromes, all important pathogenic microbes and the diseases they cause, plus a number of specialised topics useful to the practitioner.
Abstract: This updated and expanded edition now offers 297 chapters that cover the basic principles of diagnosis and management, major clinical syndromes, all important pathogenic microbes and the diseases they cause, plus a number of specialised topics useful to the practitioner. It contains 24 totally-new chapters, offers a whole section on AIDS with seven chapters and a chapter "Microsporidium Disease", which deals with a new disease just discovered because of AIDS. The text is designed for clinical pathologists, microbiologists, virologists, medical scientists, mycologists, allergists, general practitioners and lecturers of medicine.

13,514 citations

Journal ArticleDOI
TL;DR: Changing the use of tetracyclines in human and animal health as well as in food production is needed if this class of broad-spectrum antimicrobials through the present century is to continue to be used.
Abstract: Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

3,647 citations


"Acquired Antibiotic Resistance Gene..." refers background in this paper

  • ...Tetracyclines were the first major group to which the term “broad spectrum” was applied (Chopra and Roberts, 2001)....

    [...]

  • ...TETRACYCLINE History and action mechanism The first tetracycline antibiotic was characterized in 1948 as chlortetracycline from Streptomyces aureofaciens (Chopra et al., 1992; Chopra and Roberts, 2001)....

    [...]

  • ..., anhydrotetracycline and 6-thiatetracycline), see below (Rasmussen et al., 1991; Oliva and Chopra, 1992; Chopra and Roberts, 2001)....

    [...]

  • ..., oxytetracycline, tetracycline) or products of semi-synthetic approaches (e.g., doxycycline, minocycline; Chopra et al., 1992; Hunter and Hill, 1997; Chopra and Roberts, 2001)....

    [...]

Journal ArticleDOI
18 May 2000-Nature
TL;DR: Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms.
Abstract: Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes in which substantial amounts of DNA are introduced into and deleted from the chromosome. These lateral transfers have effectively changed the ecological and pathogenic character of bacterial species.

3,640 citations


"Acquired Antibiotic Resistance Gene..." refers background in this paper

  • ...…DNA mutations, which alter existing bacterial proteins, through transformation which can create mosaic proteins and/or as a result of transfer and acquisition of new genetic material between bacteria of the same or different species or genera (Spratt, 1994; Maiden, 1998; Ochman et al., 2000)....

    [...]

  • ...These AR phenotypes can be achieved in microorganisms by chromosomal DNA mutations, which alter existing bacterial proteins, through transformation which can create mosaic proteins and/or as a result of transfer and acquisition of new genetic material between bacteria of the same or different species or genera (Spratt, 1994; Maiden, 1998; Ochman et al., 2000)....

    [...]

Journal ArticleDOI
TL;DR: Extended-spectrum β-lactamases represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
Abstract: Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

3,308 citations


"Acquired Antibiotic Resistance Gene..." refers background in this paper

  • ...…at their active site, whereas Ambler class B β-lactamases are all metallo-enzymes who require zinc as a metal cofactor for their catalytic activities (Ambler, 1980; Bradford, 2001; Paterson and Bonomo, 2005; Wright, 2005; Poirel et al., 2007, 2010; Bush and Jacoby, 2010; Drawz and Bonomo, 2010)....

    [...]

  • ...The most common and important mechanism through which bacteria can become resistant against β-lactams is by expressing β-lactamases, for example extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC enzymes, and carbapenem-hydrolyzing β-lactamases (carbapenemases; Bradford, 2001; Jacoby and Munoz-Price, 2005; Paterson and Bonomo, 2005; Poirel et al., 2007; Queenan and Bush, 2007; Jacoby, 2009)....

    [...]

  • ...…expressing β-lactamases, for example extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC enzymes, and carbapenem-hydrolyzing β-lactamases (carbapenemases; Bradford, 2001; Jacoby and Munoz-Price, 2005; Paterson and Bonomo, 2005; Poirel et al., 2007; Queenan and Bush, 2007; Jacoby, 2009)....

    [...]

  • ...Ambler classes A, C, and D include the β-lactamases with serine at their active site, whereas Ambler class B β-lactamases are all metallo-enzymes who require zinc as a metal cofactor for their catalytic activities (Ambler, 1980; Bradford, 2001; Paterson and Bonomo, 2005; Wright, 2005; Poirel et al., 2007, 2010; Bush and Jacoby, 2010; Drawz and Bonomo, 2010)....

    [...]

Journal ArticleDOI
21 Aug 1992-Science
TL;DR: Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.
Abstract: The synthesis of large numbers of antibiotics over the past three decades has caused complacency about the threat of bacterial resistance. Bacteria have become resistant to antimicrobial agents as a result of chromosomal changes or the exchange of the exchange of genetic material via plasmids and transposons. Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, organisms that cause respiratory and cutaneous infections, and members of the Enterobacteriaceae and Pseudomonas families, organisms that cause diarrhea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and hospitals has fueled this crisis. Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.

2,804 citations


"Acquired Antibiotic Resistance Gene..." refers background in this paper

  • ...Nowadays numerous different classes of antimicrobial agents are known and they are classified based on their mechanisms of action (Neu, 1992)....

    [...]