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Revue Scientifique Et Technique... Apr 2012The discovery of antibiotics represented a turning point in human history. However, by the late 1950s infections that were difficult to treat, involving resistant... (Review)
Review
The discovery of antibiotics represented a turning point in human history. However, by the late 1950s infections that were difficult to treat, involving resistant bacteria, were being reported. Nowadays, multiresistant strains have become a major concern for public and animal health. Antimicrobial resistance is a complex issue, linked to the ability of bacteria to adapt quickly to their environment. Antibiotics, and antimicrobial-resistant bacteria and determinants, existed before the discovery and use of antibiotics by humans. Resistance to antimicrobial agents is a tool that allows bacteria to survive in the environment, and to develop. Resistance genes can be transferred between bacteria by horizontal transfer involving three mechanisms: conjugation, transduction and transformation. Resistant bacteria can emerge in any location when the appropriate conditions develop. Antibiotics represent a powerful selector for antimicrobial resistance in bacteria. Reducing the use of antimicrobial drugs is one way to control antimicrobial resistance; however, a full set of measures needs to be implemented to achieve this aim.
Topics: Adaptation, Physiological; Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Humans; Metagenome; R Factors
PubMed: 22849265
DOI: 10.20506/rst.31.1.2098 -
Bulletin of the World Health... 1983The development of antimicrobial drugs, and particularly of antibiotics, has played a considerable role in substantially reducing the morbidity and mortality rates of...
The development of antimicrobial drugs, and particularly of antibiotics, has played a considerable role in substantially reducing the morbidity and mortality rates of many infectious diseases. However, the fact that bacteria can develop resistance to antibiotics has produced a situation where antimicrobial agents are losing their effectiveness because of the spread and persistence of drug-resistant organisms. To combat this, more and more antibiotics with increased therapeutic and prophylactic action will need to be developed.This article is concerned with antibiotic resistance in bacteria which are pathogenic to man and animals. The historical background is given, as well as some information on the present situation and trends of antibiotic resistance to certain bacteria in different parts of the world. Considerable concern is raised over the use of antibiotics in man and animals. It is stated that antibiotic resistance in human pathogens is widely attributed to the "misuse" of antibiotics for treatment and prophylaxis in man and to the administration of antibiotics to animals for a variety of purposes (growth promotion, prophylaxis, or therapy), leading to the accumulation of resistant bacteria in their flora. Factors favouring the development of resistance are discussed.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Drug Utilization; Humans; R Factors
PubMed: 6603914
DOI: No ID Found -
Journal of Biochemistry Jan 1998Resistance to antibiotics and other chemotherapeutic agents is becoming a wide spread health issue. The biochemical mechanisms of resistance vary, but active efflux of... (Review)
Review
Resistance to antibiotics and other chemotherapeutic agents is becoming a wide spread health issue. The biochemical mechanisms of resistance vary, but active efflux of the toxic agents is one of the most common. Bacterial resistances to metals provide good model systems for transport-related resistances. One of the best understood metal resistance systems is the product of the ars operon, which provides resistance to arsenicals and antimonials. As a reflection of the ubiquity of arsenic in the environment, ars operons are found in all species of bacteria, carried in chromosomes, plasmids, and transposons. This review focuses on the biochemistry of the proteins of the ars operon of R-factor R773. The system is novel in several respects. First, it is regulated at the transcriptional and allosteric levels, and regulation is effected through cysteine thiol interaction with As(III) or Sb(III). Thus soft metal-thiol chemistry provides a high affinity digital switch to turn the regulated protein on with rapidity. The transport system that provides resistance, on the other hand, uses oxyanions of arsenic or antimony as substrates. This nonmetal chemistry allows for low affinity interactions of the membrane transporter with substrate, conductive with translocation and release of substrate on the outside of the cell membrane. Second, the transporter is uniquely capable of coupling to either electrochemical energy as a secondary carrier protein or the chemical energy of ATP when binding of a catalytic subunit converts it into an anion-translocating ATPase.
Topics: Adenosine Triphosphatases; Amino Acid Sequence; Antimony; Arsenicals; Arsenite Transporting ATPases; Drug Resistance, Microbial; Ion Pumps; Molecular Sequence Data; Multienzyme Complexes; Prokaryotic Cells; R Factors
PubMed: 9504403
DOI: 10.1093/oxfordjournals.jbchem.a021904 -
Journal of Bacteriology Oct 1976The R-factor RP1 was transferred by conjugation from Pseudomonas aeruginosa PAO12r(RPI) to various strains of Erwinia herbicola and to one strain of Erwinia stewartii....
The R-factor RP1 was transferred by conjugation from Pseudomonas aeruginosa PAO12r(RPI) to various strains of Erwinia herbicola and to one strain of Erwinia stewartii. The exconjugate strains had minimum inhibitory concentration values for carbenicillin, kanamycin, neomycin, and tetracycline somewhat lower than the corresponding values for the pseudomonad RP1 donor strain. The biochemical characteristics of the exconjugant strains displayed minor variation in some instances from those of the corresponding R- strains. Sensitivity of the RP1+ strains to the RP1-specific bacteriophages PRD1 and PRR1 varied from an efficiency of plating [compared with P. aeruginosa PA067(RP1)] of 0 [E. herbicola Y46(RP1)] to 133 [E. herbicola Y190(RP1)] and 148 [E. stewartii SS104R(RP1)] for PRD1, and from 0 [E. herbicola Y46(RP1)] to 0.0002 [E. herbicola Y185(RP1)] and 18.4 [E. stewartii SS104R(RP1)] for PRR1. The phage-resistant strain E. herbicola Y46(RP1), would donate, by conjugation, the R-factor to E. herbicola Y46rifr, P, aeruginosa PAT900, or Escherichia coli UB1005 only at extremely low frequencies, if at all. Transformation of E. coli JC7620 by covalently closed circular DNA from E. herbicola Y46(RP1) gave and E. coli R+ strain exhibiting the expected antibiotic resistance pattern and having the ability to donate RP1 by conjugation. It is suggested (i) that some strains of E. herbicola RP1 either do not produce RP1 pili or produce defective pili, and (ii) that sensitivity to the bacteriophages PRD1 and PRR1 is not a suitable means of diagnosing the presence RP1 in E. herbicola strains.
Topics: Bacteriophages; Conjugation, Genetic; DNA, Bacterial; DNA, Circular; Drug Resistance, Microbial; Erwinia; Pseudomonas aeruginosa; R Factors; Transformation, Genetic; Viral Plaque Assay
PubMed: 824272
DOI: 10.1128/jb.128.1.309-316.1976 -
Journal of Bacteriology Jul 1975When Proteus mirabilis harboring the R factor NR1 is cultured in Penassay broth containing 100 mug of chloramphenicol (CM) per ml, there is an amplification in the...
When Proteus mirabilis harboring the R factor NR1 is cultured in Penassay broth containing 100 mug of chloramphenicol (CM) per ml, there is an amplification in the number of copies of the r-determinants per cell. Under these conditions, R factors harboring multiple tandem sequences of r-determinants are formed. Autonomous poly-f-determinants consisting of multiple copies of r-determinants are also formed. This phenomenon has been referred to as the "transition". Transitioned cells have considerably higher levels of resistance to CM and streptomycin (SM), but not to tetracycline (TC), than do nontransitioned cells and grow more rapidly in medium containing either CM or SM. There is essentially no difference in growth rates between transitioned and nontransitioned cells in drug-free medium. The higher level of resistance of transitioned cells to SM has made it possible to investigate the mechanism of the transition. Using replica plating, it has been possible to isolate spontaneously occurring transitioned cells from a nontransitioned population which appear to outgrow the nontransitioned cells during growth in medium containing 100 mug of CM per ml. If transiitoned cells are subsequently cultured in drug-free medium, the cells return gradually to the nontransitioned state, which has been referred to as the "back-transition was monitored by examining the level of resisitance of the cells to SM. In both situations the cell populations were found to be heterogeneous, consisting of a mixture of nontransitioned and transitioned cells. Under the conditions of our experiments, the transition appeared to be due to the more rapid growth of a minor fraction of spontaneously occurring transitioned cells which outgrew the remainder of cells in the population. To obtain the transition, the drug resistance gene must reside on the r-determinants component of the R factor. The transition did not take place when the cells were cultured in medium containing high concentrations of TC. This indicates that the TC resistance genes reside on the resistance transfer factor component of the R factor, which is in agreement with physical studies on R factor deoxyribonucleic acid.
Topics: Bacteriological Techniques; Chloramphenicol; Conjugation, Genetic; Culture Media; DNA Replication; DNA, Bacterial; Drug Resistance, Microbial; Genes; Mutation; Proteus mirabilis; R Factors; Streptomycin; Tetracycline
PubMed: 1095563
DOI: 10.1128/jb.123.1.56-68.1975 -
EMBO Reports May 2007Plasmids are units of extrachromosomal genetic inheritance found in all kingdoms of life. They replicate autonomously and undergo stable propagation in their hosts.... (Review)
Review
Plasmids are units of extrachromosomal genetic inheritance found in all kingdoms of life. They replicate autonomously and undergo stable propagation in their hosts. Despite their small size, plasmid replication and gene expression constitute a metabolic burden that compromises their stable maintenance in host cells. This pressure has driven the evolution of strategies to increase plasmid stability--a process accelerated by the ability of plasmids to transfer horizontally between cells and to exchange genetic material with their host and other resident episomal DNAs. These abilities drive the adaptability and diversity of plasmids and their host cells. Indeed, survival functions found in plasmids have chromosomal homologues that have an essential role in cellular responses to stress. An analysis of these functions in the prokaryotic plasmid R1, and of their intricate interrelationships, reveals remarkable overall similarities with other gene- and cell-survival strategies found within and beyond the prokaryotic world.
Topics: Bacteria; Base Sequence; Drug Resistance, Bacterial; Gene Dosage; Gene Transfer, Horizontal; Molecular Sequence Data; R Factors; Replicon
PubMed: 17471262
DOI: 10.1038/sj.embor.7400957 -
Protein Science : a Publication of the... May 2015Crystallographic R work and R free values, which are measures of the ability of the models of macromolecular structures to explain the crystallographic data on which...
Crystallographic R work and R free values, which are measures of the ability of the models of macromolecular structures to explain the crystallographic data on which they are based, are often used to assess structure quality. It is widely known, and confirmed here that both are sensitive to the methods used to compute them, and can be manipulated to improve the apparent quality of the model. As an alternative it is proposed here that the quality of crystallographic models should be assessed using a global goodness-of-fit metric RO2A /R work where RO2A is the number of reflections used for refinement divided by the number of nonhydrogen atoms in the structure, and R work is the working R-factor of the refined structure. Also, analysis of structures in the Protein Data Bank suggests that many data sets have been truncated at high resolution, thereby improving the R-factor statistics. To discourage this practice, it is proposed that the resolution of a dataset be defined as the resolution of the shell of data where falls to 1. The proposed goodness-of-fit metric encourages investigators to use all the data available rather than a truncated subset.
Topics: Crystallography, X-Ray; Databases, Protein; Models, Molecular; Molecular Structure; Protein Conformation; Proteins; Tetrahydrofolate Dehydrogenase
PubMed: 25581292
DOI: 10.1002/pro.2639 -
Microbiology and Molecular Biology... Jun 2003Conjugative transfer of bacterial plasmids is the most efficient way of horizontal gene spread, and it is therefore considered one of the major reasons for the increase... (Review)
Review
Conjugative transfer of bacterial plasmids is the most efficient way of horizontal gene spread, and it is therefore considered one of the major reasons for the increase in the number of bacteria exhibiting multiple-antibiotic resistance. Thus, conjugation and spread of antibiotic resistance represents a severe problem in antibiotic treatment, especially of immunosuppressed patients and in intensive care units. While conjugation in gram-negative bacteria has been studied in great detail over the last decades, the transfer mechanisms of antibiotic resistance plasmids in gram-positive bacteria remained obscure. In the last few years, the entire nucleotide sequences of several large conjugative plasmids from gram-positive bacteria have been determined. Sequence analyses and data bank comparisons of their putative transfer (tra) regions have revealed significant similarities to tra regions of plasmids from gram-negative bacteria with regard to the respective DNA relaxases and their targets, the origins of transfer (oriT), and putative nucleoside triphosphatases NTP-ases with homologies to type IV secretion systems. In contrast, a single gene encoding a septal DNA translocator protein is involved in plasmid transfer between micelle-forming streptomycetes. Based on these clues, we propose the existence of two fundamentally different plasmid-mediated conjugative mechanisms in gram-positive microorganisms, namely, the mechanism taking place in unicellular gram-positive bacteria, which is functionally similar to that in gram-negative bacteria, and a second type that occurs in multicellular gram-positive bacteria, which seems to be characterized by double-stranded DNA transfer.
Topics: Amino Acid Sequence; Base Sequence; Conjugation, Genetic; DNA, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Molecular Sequence Data; Plasmids; R Factors; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid
PubMed: 12794193
DOI: 10.1128/MMBR.67.2.277-301.2003 -
Journal of Bacteriology Sep 1975The structure of R factor NR1 DNA in Proteus mirabilis has been studied by using the techniques of CsCl density gradient centrifugation, sedimentation in neutral and...
The structure of R factor NR1 DNA in Proteus mirabilis has been studied by using the techniques of CsCl density gradient centrifugation, sedimentation in neutral and alkaline sucrose gradients, and electron microscopy. It has been shown that the nontransitioned form of NR1 DNA isolated from P. mirabilis cultured in drug-free medium is a37-mum circular deoxyribonucleic acid (DNA) with a density of 1.712 g/ml in a neutral CsCl gradient. This circular molecule is a composite structure consisting of a 29-mum resistance transfer factor containing the tetracycline-resistance genes (RTF-TC) and an 8-mum r-determinants component conferring resistance to chloramphenicol (CM), streptomycin/spectinomycin, and the sulfonamides. There are one to two copies of NR1 per chromosome equivalent of DNA in exponential-phase cells cultured in Penassay broth. After growth of PM15/NR1 in medium containing 100 mug of CM per ml, the density of the NR1 DNA increased from 1.712 g/ml to approximately 1.718 g/ml and the proportion of NR1 DNA relative to the chromosome is amplified about 10-fold. The changes in R factor DNA structure which accompany this phenomenon (termed the transition) have been studied. DNA density profiles of the transitioned NR1 DNA consist of a 1.718 g/ml band which is skewed toward the less dense side. The transitioned NR1 DNA consists of molecules containing the RTF-TC element attached to multiple copies of r-determinants DNA (poly-r-determinant R factors) and multimeric and monomeric autonomous r-determinants structures. Poly-r-determinant R factors have a density intermediate between the basic composite structure (1.712 g/ml) and r-determinants DNA (1.718 g/ml). These species presumably account for the skewing of the 1.718-g/ml DNA band toward the less dense side. When transitioned cells are subsequently cultured in drug-free medium, poly-r-determinant R factors and autonomous poly-r-determinants undergo dissociation to form smaller structures containing fewer copies of r-determinants. This process continues until, after prolonged growth in drug-free medium the NR1 DNA returns to the nontransitioned state which consists of an RTF-TC and a single copy of r-determinants.
Topics: Chloramphenicol; Chromosomes, Bacterial; DNA; DNA Replication; DNA, Bacterial; DNA, Circular; DNA, Satellite; Drug Resistance, Microbial; Genes; Molecular Weight; Plasmids; Proteus mirabilis; R Factors
PubMed: 1099069
DOI: 10.1128/jb.123.3.1013-1034.1975 -
Journal of Bacteriology Sep 1975The R factor NR1 consists of two components: a resistance transfer factor which harbors the tetracycline resistance genes (RTF-TC) and the r-determinants component which...
The R factor NR1 consists of two components: a resistance transfer factor which harbors the tetracycline resistance genes (RTF-TC) and the r-determinants component which harbors the other drug resistance genes. Using partial denaturation mapping it is possible to distinguish the RTF-TC region from the r-determinants region of the composite R factor NR1 DNA which has a contour length of 37 mum and a density of 1.712 g/ml. The r-determinants region was a relatively undenatured 8.5-mum segment of the molecule when the deoxyribonucleic acid was partially denatured at pH 10.7. An RTF-TC genetic segregant of NR1 which had lost the r-determinants component had a contour length of 28.7 mum and a density of 1.710 g/ml. Characterization of an RTF-TC using partial denaturation mapping at pH 10.7 confirmed that the relatively undenatured 8.5-mum r-determinants segment of the composite R factor had been deleted. Circular, transitioned NR1 DNA molecules (1.716 to 1.718 g/ml), whose contour lengths were consistent with an RTF-TC plus an integral number of tandem copies of r-determinants, were also characterized by denaturation mapping. The relatively undenatured region in these molecules had a length equal to an integral number of copies of r-determinants and was located at the same site in the partially denatured RTF-TC as the single copy of r-determinants in the 37-mum composite NR1. This indicates that there is a unique integration site for r-determinants in the RTF-TC component. The R factor UCR122, a TC deletion mutant of NR1, was also characterized by denaturation mapping. The translocation of the TC resistance gene(s) on the denaturation map permitted the alignment of the denaturation map with the heteroduplex map of Sharp et al. (u073). Linear and circular monomeric and presumed multimeric r-determinants DNA molecules (p = 1.718 g/ml) were partially denatured at a higher pH (11.10). The r-determinants multimers showed a repeating 8.3-mum (monomeric) partial denaturation pattern indicating a head-to-tail arrangement of monomers in these poly-r-determinant molecules.
Topics: DNA, Bacterial; DNA, Circular; DNA, Satellite; Drug Resistance, Microbial; Genes; Mutation; Nucleic Acid Denaturation; Proteus mirabilis; R Factors
PubMed: 1099070
DOI: 10.1128/jb.123.3.1035-1042.1975