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Results for “resistance evolution”

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PubMed1979

Evolution of multiple-antibiotic-resistance plasmids mediated by transposable plasmid deoxyribonucleic acid sequences.

Two plasmid deoxyribonucleic acid sequences mediating multiple antibiotic resistance transposed in vivo between coexisting plasmids in clinical isolates of Serratia marcescens. This event resulted in the evolution of a transferable multiresistance plasmid. Both sequences, designated in Tn1699 and Tn1700, were flanked by inverted deoxyribonucleic acid repetitions and could transpose between replicons independently of the Excherichia coli recA gene function. Tn1699 and Tn1700 mediated ampicillin, carbenicillin, kanamycin, and gentamicin resistance but differed in the type of gentamicin-acetyltransferase enzymes that they encoded. The structural genes for these enzymes share a great deal of polynucleotide sequence similarity despite their phenotypic differences. The transposition of Tn1699 and Tn1700 to coresident transferable plasmids has contributed to the dissemination of antibiotic resistance among other gram-negative bacteria. These organisms have recently caused nosocomial infections in epidemic proportions.

Anti-Bacterial Agents↗

PubMed2002

Immune responses to myxoma virus.

Myxoma virus causes the systemic disease myxomatosis in the European rabbit (Oryctolagus cuniculus). Originating in the South American rabbit Sylvilagus brasiliensis, where it causes a relatively localized fibroma, myxoma virus is a classic example of a virus that has jumped species to produce an exotic disease and then coevolved with its new host. Like other poxviruses, myxoma virus encodes multiple proteins capable of downregulating the host innate and acquired immune responses. Other virus-encoded proteins enable replication in host lymphocytes and monocytes, for example, by inhibiting apoptosis. Detailed studies on these proteins have demonstrated novel methods of interactions with the host immune system and added substantially to the understanding of the interaction of large DNA viruses with their hosts. Despite the increasingly detailed molecular knowledge of myxoma virus, relatively little is known about the dynamics of the interaction of the virus with the integrated host-immune system during infection and, in particular, about the evolution of resistance to the virus in wild rabbits or the species barrier. This review will focus on the detailed molecular studies that have been done with myxoma virus and discuss the more limited knowledge of the pathogenesis of myxoma virus in rabbits and the ways that the consolidated immune responses may determine genetic resistance to myxomatosis.

Animals↗

PubMed2004

The genetics and genomics of insecticide resistance.

The past ten years have seen the elucidation of the molecular basis of insect resistance to many chemical insecticides. Target genes, mostly in the nervous system, have been identified and cloned from Drosophila melanogaster and resistance-associated mutations have been examined in a range of pest insects. More recently, with the advent of annotated insect genomes, resistance mediated by complex multi-gene enzyme systems such as esterases, cytochrome p450s and glutathione-S-transferases has also been elucidated. In this article, we review the impact of Drosophila genetics on the field of insect resistance and focus on the current and future impact of genomics. These studies enable us to address three fundamental questions in the evolution of resistance. How many genes are involved? How many mutations are there within these genes? How often do these mutations arise in natural populations?

Acetylcholinesterase↗

PubMed2006

Replicon typing of plasmids encoding resistance to newer beta-lactams.

Polymerase chain reaction-based replicon typing represents a novel method to describe the dissemination and follow the evolution of resistance plasmids. We used this approach to study 26 epidemiologically unrelated Enterobacteriaceae and demonstrate the dominance of incompatibility (Inc) A/C or Inc N-related plasmids carrying some emerging resistance determinants to extended-spectrum cephalosporins and carbapenems.

Anti-Bacterial Agents↗

PubMed2005

Is antibiotic resistance a problem? A practical guide for hospital clinicians.

Antibiotic resistance is an important concern for patients, physicians, healthcare managers, and policymakers. Inappropriate antimicrobial prescribing fuels the evolution of resistance, while poor basic hygiene facilitates the spread of resistant microbes between patients and healthcare staff. The development of infection with a resistant pathogen may lead to poorer health and economic outcomes. The problem for the frontline clinician, however, is how to balance the responsibility of prudent prescribing with the risk of sub-optimally treating a patient who may be infected with a resistant pathogen. This article discusses how hospital physicians can use severity and risk factor assessment, and knowledge of local microbial epidemiology, to guide empiric antibiotic prescribing. Most patients hospitalised with a community acquired bacterial infection in the UK can still be managed with a traditional first line antibiotic(s). In contrast, regimens that account for resistance are often required in patients with hospital acquired infections, particularly if the patient is critically ill.

Anti-Bacterial Agents↗

PubMed2001

Hospital-acquired pneumonia: risk factors, microbiology, and treatment.

Pneumonia complicates hospitalization in 0.5 to 2.0% of patients and is associated with considerable morbidity and mortality. Risk factors for hospital-acquired pneumonia (HAP) include mechanical ventilation for > 48 h, residence in an ICU, duration of ICU or hospital stay, severity of underlying illness, and presence of comorbidities. Pseudomonas aeruginosa, Staphylococcus aureus, and Enterobacter are the most common causes of HAP. Nearly half of HAP cases are polymicrobial. In patients receiving mechanical ventilation, P aeruginosa, Acinetobacter, methicillin-resistant S aureus, and other antibiotic-resistant bacteria assume increasing importance. Optimal therapy for HAP should take into account severity of illness, demographics, specific pathogens involved, and risk factors for antimicrobial resistance. When P aeruginosa is implicated, monotherapy, even with broad-spectrum antibiotics, is associated with rapid evolution of resistance and a high rate of clinical failures. For pseudomonal HAP, we advise combination therapy with an antipseudomonal beta-lactam plus an aminoglycoside or a fluoroquinolone (eg, ciprofloxacin).

Anti-Bacterial Agents↗

PubMed1996

Genetic analysis of coevolution between plants and their natural enemies.

Plants exhibit a diverse array of characteristics that have been interpreted as functioning primarily as defenses against natural enemies, such as pathogens and herbivores. Recent genetic analyses of resistance provide evidence supporting this interpretation. In addition, these analyses also support a key assumption underlying models of the evolution of resistance (i.e. that resistance is costly) and suggest that the outcome of coevolution is often not explainable in terms of pairwise interactions between a plant and individual natural enemies (i.e. coevolution is often likely to be diffuse rather than pairwise).

Animals↗

PubMed2004

Antibiotic-induced lateral transfer of antibiotic resistance.

As do many temperate bacteriophages, integrating conjugative elements (ICEs) recruit the SOS DNA damage response to mobilize themselves from the bacterial chromosome and infect other cells. This transfers resistance to multiple antibiotics. Several commonly used antibiotics induce the SOS response, potentially hastening genetic change and the evolution to resistance of pathogenic populations. The use of such antibiotics should be reconsidered.

Anti-Bacterial Agents↗

PubMed2001

High levels of resistance to metronidazole and clarithromycin in Helicobacter pylori strains in children.

The aim of the study was to evaluate the prevalence of resistance to amoxicillin, metronidazole, and clarithromycin before treatment of Helicobacter pylori infection in children and to assess the evolution of resistance with time. The study was carried out between 1994 and 1999 with 150 H. pylori-positive children through gastric culture (antimicrobial susceptibility) and histology. All cultured H. pylori strains were sensitive to amoxicillin, 64 (43%) were resistant to metronidazole, 32 (21%) were resistant to clarithromycin, and 14 (9%) were resistant to both metronidazole and clarithromycin. The overall prevalence of resistance to metronidazole and clarithromycin did not change significantly with time. The study highlights the generalized high-level and stable metronidazole and clarithromycin resistance of H. pylori strains from children.

Adolescent↗

PubMed2003

Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain.

The temporal dynamics of penicillin and erythromycin co-resistance in Streptococcus pneumoniae based on two extensive multicentre Spanish surveillance SAUCE studies (1996-1997 and 1998-1999) is presented. Erythromycin resistance among penicillin non-susceptible isolates seems to have reached a limit as evidenced by a null increase between the two surveys, whereas it is growing among penicillin-susceptible pneumococci.

Drug Resistance, Bacterial↗

PubMed2005

Pharmacodynamic modeling of ciprofloxacin resistance in Staphylococcus aureus.

Three pharmacodynamic models of increasing complexity, designed for two subpopulations of bacteria with different susceptibilities, were developed to describe and predict the evolution of resistance to ciprofloxacin in Staphylococcus aureus by using pharmacokinetic, viable count, subpopulation, and resistance mechanism data obtained from in vitro system experiments. A two-population model with unique growth and killing rate constants for the ciprofloxacin-susceptible and -resistant subpopulations best described the initial killing and subsequent regrowth patterns observed. The model correctly described the enrichment of subpopulations with low-level resistance in the parent cultures but did not identify a relationship between the time ciprofloxacin concentrations were in the mutant selection window (the interval between the MIC and the mutant prevention concentration) and the enrichment of these subpopulations. The model confirmed the importance of resistant variants to the emergence of resistance by successfully predicting that resistant subpopulations would not emerge when a low-density culture, with a low probability of mutants, was exposed to a clinical dosing regimen or when a high-density culture, with a higher probability of mutants, was exposed to a transient high initial concentration designed to rapidly eradicate low-level resistant grlA mutants. The model, however, did not predict or explain the origin of variants with higher levels of resistance that appeared and became the predominant subpopulation during some experiments or the persistence of susceptible bacteria in other experiments where resistance did not emerge. Continued evaluation of the present two-population pharmacodynamic model and development of alternative models is warranted.

Anti-Infective Agents↗

PubMed1995

Resistance mechanisms to arsenicals and antimonials.

Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.

Animals↗

PubMed1985

MLS-resistance determinants in Staphylococcus aureus and their molecular evolution.

This paper describes the genetic phenomenology of resistance to macrolide-lincosamide-streptogramin B antibiotics (MLSr) in Staphylococcus aureus and attempts to place this phenomenology in a broad evolutionary context. As antibiotic resistance in general and MLS resistance in particular are typical variable traits in bacteria of clinical interest, we shall begin by introducing the concept of variable genetic traits, as outlined in Figure 1. Variable traits are those that are expressed by some strains of a given species but not by others--in comparison to constant traits which are always present as part of the standard genetic make-up of the species and have constant chromosomal locations. Variable traits are often associated with variable and mobile genetic elements and it is suggested that, in general, they are not likely to have evolved as such in the species in which they are found. Rather, they will most probably have evolved as constant (chromosomal) traits in other species and acquired genetic mobility much later as a rare occurrence in that species. These rarely occurring mobile variants would then spread horizontally within a range of new species. The MLSr determinants in Gram-positive bacteria would appear to represent a classic example of this process. Their remarkable variability will be described as the extant end-point of the process and a probable evolutionary pathway will be traced back to the streptomycetes which are a likely primary source.

Anti-Bacterial Agents↗

PubMed2006

Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and lung resistance protein (LRP) during the evolution of overt leukemia in myelodysplastic syndromes.

It is well-known that leukemic cells of overt leukemia (OL) that have transformed from myelodysplastic syndromes (MDS) are more resistant to chemotherapy as compared with de novo AML cells. Thus, to examine the expression levels of drug-resistant genes and their alterations with the development of OL in MDS, the expression of mRNA for MDR1 and LRP was determined in bone marrow samples from control, de novo AML, MDS, MDS at the time of OL transformation (MDS --> OL), and after transformation (OL) by quantitative real-time RT-PCR. The expression of MDR1 in MDS bone marrow at the time of initial diagnosis was as low as that for control subjects. However, the expression level was significantly elevated at the time of the development of OL (MDS --> OL) compared with the initial MDS subjects (P < 0.05), while expression was relatively reduced after OL development (OL). The expression of LRP was significantly higher in MDS and MDS --> OL samples than control subjects. However, the high expression of LRP in MDS --> OL was significantly reduced after OL development (OL). The expression levels of drug-resistant genes in MDS --> OL or OL were not significantly higher than those of de novo AML samples, although LRP expression in MDS or MDS --> OL was relatively higher than that of de novo AML. Detecting increases in the expression of MDR1 would be useful for predicting OL development in MDS patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Alcohol consumption and insulin resistance syndrome parameters: associations and evolutions in a longitudinal analysis of the French DESIR cohort.

PURPOSE: To determine the effects of average alcohol consumption and changes in alcohol intake on the insulin resistance syndrome parameters in a 3-year follow-up study. METHODS: Longitudinal study of 1856 and 1529 alcohol drinking men and women in the French DESIR study (Data from an Epidemiological Study on the Insulin Resistance syndrome), aged 30 to 64 years. RESULTS: In men, fasting glucose, body mass index, waist circumference, systolic blood pressure, and HDL-cholesterol were positively associated with average alcohol consumption while there was no association with insulin or triglycerides concentrations. A change in alcohol intake was positively associated with HDL-cholesterol concentration and systolic blood pressure at follow-up. These effects of alcohol could not be attributed specifically to the intake of wine. In women, while the alcohol HDL-cholesterol relation was similar to that found in the men, the only significant effect of average alcohol intake was an increase in systolic blood pressure, with a spurious decrease in blood pressure related to a 3-year increase in alcohol intake. CONCLUSIONS: Alcohol only provided a beneficial effect on HDL-cholesterol. The beneficial effect seen by other authors of moderate alcohol drinking on diabetes and cardiovascular risk may be due to effects on parameters other than those included in the current definitions of the insulin resistance syndrome.

Adult↗

PubMed2006

Genetic variation and covariation for resistance and tolerance to Cucumber mosaic virus in Mimulus guttatus (Phrymaceae): a test for costs and constraints.

Genetic variation for resistance and tolerance to pathogens may be maintained by costs represented as genetic tradeoffs between these traits and fitness. The evolution of resistance and tolerance also may be constrained by negative genetic correlations between these defense systems. Using a complete diallel, we measured genetic variation and covariation for and among performance, resistance, and tolerance traits in Mimulus guttatus challenged with a generalist pathogen, Cucumber mosaic virus (CMV). Viral coat protein was detected by enzyme-linked immunosorbent assay (ELISA) in all inoculated plants, indicating that all plants were susceptible to infection, although the ELISA absorbance varied quantitatively across plants. Plants inoculated with CMV had significantly reduced aboveground biomass and flower production relative to controls, although date of first flower was unaffected by infection. All three of these performance traits showed moderate to high narrow-sense heritability (h2 = 0.32-0.62) in both inoculated and control plants. We found phenotypic variation for both tolerance of and resistance to our strain of CMV, but both displayed very low narrow-sense heritability (h2 < 0.03). We found no evidence of a trade-off between resistance and tolerance. We also found no evidence for a cost of resistance or tolerance. In fact, a significant genetic correlation suggested that plants that were large when healthy had the greatest tolerance when infected. Significant, positive genetic correlations found between performance of uninfected and infected plants suggested that selection would likely favor the same M. guttatus genotypes whether CMV is present or not.

Biological Evolution↗

PubMed2026

An Acetyltransferase Conferring Self-Resistance of the Producer to Lasso Peptide Antibiotic Lariocidin.

The soil microbiome, a reservoir of antibiotic-producing bacteria, also harbors resistance determinants encoded within antibiotic biosynthetic gene clusters (BGCs). Studying self-resistance mechanisms, which have evolved in producers to protect against their own toxic metabolites, provides critical insights into the evolution of resistance and the potential vulnerabilities of new antibiotics and can facilitate the production of natural products in heterologous hosts. Here, we describe the self-resistance mechanism to lariocidin (LAR), a recently discovered lasso peptide antibiotic that inhibits the ribosomal machinery and exhibits antibacterial activity against key pathogens. We identified and characterized an N-acetyltransferase enzyme (LrcE) encoded within the LAR BGC that mediates self-resistance in LAR-producing Paenibacillus sp. M2. LrcE is a member of the GCN5-related N-acetyltransferase (GNAT) superfamily and performs site-specific acetylation of LAR at a critical lysine residue. This modification disrupts ribosomal binding, thereby reducing LAR's antibacterial activity. Using in silico modeling, we predicted a conserved acetyl-CoA-binding motif and an LAR-binding region on LrcE. Bioinformatic analysis revealed LrcE homologues in environmental but not clinically relevant pathogens, suggesting a limited risk of horizontal gene transfer and, therefore, supporting the further development of LAR as a next-generation antibiotic.

Anti-Bacterial Agents↗

PubMed1998

Evolution of an endemic methicillin-resistant Staphylococcus aureus population in an Australian hospital from 1967 to 1996.

The evolution over 30 years of a population of methicillin-resistant Staphylococcus aureus (MRSA) from a tertiary referral hospital was studied by phylogenetic analysis of SmaI-generated restriction fragment length polymorphisms (RFLPs). The results suggest that a new clone of MRSA appeared at the hospital in the early 1980s, which, although usually retaining its ancestral phage-type, developed four different RFLP pulsotypes in the next 16 years. This finding indicates that multiple RFLP patterns in MRSA do not necessarily represent multiple clones deriving from different mec gene transfer events. Such variation within a clone may be significant in the interpretation of RFLP patterns during outbreaks and emphasizes the need to use two typing methods in studies of such populations. Since the appearance of new clones of MRSA is a relatively rare event, cross-infection control is paramount in the prevention of MRSA dissemination.

Anti-Bacterial Agents↗