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PubMed2004

The dominance of the herbicide resistance cost in several Arabidopsis thaliana mutant lines.

Resistance evolution depends upon the balance between advantage and disadvantage (cost) conferred in treated and untreated areas. By analyzing morphological characters and simple fitness components, the cost associated with each of eight herbicide resistance alleles (acetolactate synthase, cellulose synthase, and auxin-induced target genes) was studied in the model plant Arabidopsis thaliana. The use of allele-specific PCR to discriminate between heterozygous and homozygous plants was used to provide insights into the dominance of the resistance cost, a parameter rarely described. Morphological characters appear more sensitive than fitness (seed production) because 6 vs. 4 differences between resistant and sensitive homozygous plants were detected, respectively. Dominance levels for the fitness cost ranged from recessivity (csr1-1, ixr1-2, and axr1-3) to dominance (axr2-1) to underdominance (aux1-7). Furthermore, the dominance level of the herbicide resistance trait did not predict the dominance level of the cost of resistance. The relationship of our results to theoretical predictions of dominance and the consequences of fitness cost and its dominance in resistance management are discussed.

Arabidopsis↗

PubMed2026

Genetic mutations driving ciprofloxacin resistance in laboratory-evolved Salmonella Typhimurium.

Ciprofloxacin resistance in Salmonella Typhimurium is a significant public health concern, and the mechanisms by which the resistance evolves are poorly defined. Here, by serial passaging under antibiotic selection, we isolated ciprofloxacin-resistant S. Typhimurium mutants and subjected them to whole-genome sequencing to reveal the major mutations associated with resistance. The Low CipR mutant acquired four chromosomal mutations in ramR, icdA, lipB, and gyrA, and the High CipR mutant gained additional mutations in gyrB, yaiC, and corA. Functional characterization determined that mutations in ramR resulted in efflux pump upregulation, while disruptions in the TCA cycle caused by mutations in icdA and lipB led to metabolic alterations. These changes indirectly enhanced resistance by increasing the expression of the global regulator MarA and reducing OmpF-dependent membrane permeability. Despite the observation of the G105A substitution in GyrA, enzymatic assays confirmed the failure to support resistance to ciprofloxacin, possibly because the structural alteration remained minimal. GyrB488-489dup was associated with maintained supercoiling under ciprofloxacin and enhanced fluoroquinolone resistance, suggesting a major role in resistance evolution. Other mutations in yaiC impaired biofilm and, in corA, intracellular accumulation of magnesium, possibly stabilizing the bacterial cell envelope under antibiotic pressure. The findings provide novel explanations for the multifaceted mechanisms leading to ciprofloxacin resistance in Salmonella and suggest targets to combat antimicrobial resistance.IMPORTANCEAntibiotic resistance in Salmonella Typhimurium is an increasing public health concern, yet the genetic changes that allow bacteria to become resistant are not fully understood. In this study, we evolved ciprofloxacin-resistant Salmonella in the laboratory and identified the mutations that arise during resistance development. We found that resistance does not result from a single change but from multiple adaptations affecting drug efflux, metabolism, and the antibiotic target. Some mutations increased the activity of pumps that remove antibiotics from the cell, while others altered bacterial metabolism and reduced membrane permeability, making it harder for the drug to enter. A duplication in the DNA gyrase subunit GyrB played a particularly important role in maintaining DNA function under antibiotic stress. Together, these results reveal how diverse genetic changes cooperate to generate ciprofloxacin resistance and provide insights that may help guide strategies to combat drug-resistant Salmonella infections.

DNA gyrase↗

PubMed2005

[Enterococcal bacteremia at Nîmes university hospital].

PURPOSE OF THE STUDY: The aim of this study was the description of enterococcal bacteremia and the evaluation of their resistance evolution to antibiotics and the virulence profile of these isolates. PATIENTS AND METHODS: We have studied all the bacteremia caused by Enterococcus spp. from the 1st of July 2003 until the 30th of June 2004 at Nîmes university hospital. For each isolate, population, clinical and microbiological data were collected. Multiplex PCR allowed for the identification of glycoprotein resistant phenotypes and furthermore, to identify the main virulence genes found in the enterococci. RESULTS: Thirty-three strains were identified from 33 patients (60.6% male) with a median age of 68 years (median: 3-96). The vital prognostic was calculated in 63.6% of the cases (MacCabe > or =1); seven patients died during their hospitalization (21.2%). The infections were nosocomial in 60.6% of the cases. No epidemic was observed. The principal comorbidities were cardiovascular and digestive pathologies. In addition, 54.5% of patients had had a surgical intervention. Enterococcus faecalis (87.9%) was the cause of infection in the majority of cases followed by Enterococcus faecium. Most of the infections were monomicrobial (75.8%). E. faecalis was sensitive to amoxicillin and to glycopeptides but was resistant to norfloxacin, erythromycin and pristinamycin. The same observations were made for the E. faecium with the exception of amoxicillin. E. faecalis had the maximum number of virulence genes and E. faecium the least. CONCLUSION: The enterococcal bacteremia had mainly a nosocomial origin. The isolates came from digestive tract flora but also from catheters. The mortality rate was 21.2%. A developing sensitivity to erythromycin and pristinamycin was observed in comparison to the data of the ONERBA (2002-2003). Only one isolate was resistant to glycopeptide. This was the first European E. faecium containing the vanD allele. This isolate proved fatal to the patient. The dark evolution of enterococcal bacteremia and their frequent nosocomial origin induce to promote studies intended for better knowing the risk factors of such infections.

Adolescent↗

PubMed1979

Chronic non-specific ulcerative duodenojejunoileitis: report of four cases.

Four patients with chronic non-specific ulcerative duodenojejunoileitis (CNSUDJI) are reported. The clinical picture included abdominal pain, fever, and a malabsorption syndrome. Main rediological findings were diffuse narrowing of the jejunal loops with total effacement of the mucosal folds. Multiple peroral biopsies of the small intestine showed various degrees of mucosal abnormalities from total villous atrophy to normal villi, but ulcerations were diagnosed only by operative full thickness biopsies or resection of the small bowel. The ulcerative process was associated with well-documented coeliac disease in two patients: in one of them it occurred as a fatal complication involving also the colon, three years after the start of a gluten free diet, while the disease was in full clinical and histological remission. In the other case, coeliac disease was revealed by obstructive symptoms due to stenosing ulcerations; five months after surgical resection of the stenosis, institution of a gluten free diet induced a dramatic improvement. In the two other patients ulcerations were not associated with coeliac disease: one of them had a patchy villous atrophy and resisted a gluten free diet and total parenteral nutrition; she was improved by and dependent upon steroids but finally died. The last patient had normal villous height; ulcerations were located exclusively along the mesenteric border of the small bowel; he had a low-grade protracted evolution resisting any form of therapy and developed a peripheral neuropathy of unknown aetiology. On the basis of our cases and of a review of the literature the discussion focuses on the difficulty in diagnosing CNSUDJI, its relationship with coeliac disease, and its management and prognosis.

Adult↗

PubMed2002

The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.

BACKGROUND: Overuse of antimicrobial drugs has resulted in an alarming increase in bacterial resistance in most countries. The relevance for general practice is unknown. OBJECTIVE: To evaluate the impact of the sale of antimicrobial drugs on bacterial resistance as found in uropathogens from general practice. SETTING: General practice in Belgium and Norway. METHODS: Observational study. RESULTS: The sale of antimicrobial drugs indicated for use in the treatment of urinary tract infection was four times higher in Belgium than in Norway (18.5 vs 4.4 DDD/1000 inhabitants/day). The antibiotic resistance reported by microbiological laboratories as valid for general practice was significant higher in Belgium than in Norway (ampicillins (44% vs 27%), co-trimoxazole (28% vs 17%), fluoroquinolones (12% vs 2%) and nitrofurantoin (16% vs 11%, p < 0.0001 for all). However, the antibiotic resistance found in urine samples from dysuric women in general practice was similar (trimethoprim 14% vs 12%, co-trimoxazole 14% vs 11%, nitrofurantoin 7% vs 3%), except in the case of ampicillins (30% vs 19%, p < 0.05). CONCLUSION: The impact of the antimicrobial sale on resistance in uropathogens seems less than expected at the general practice level, even though local microbiological reports mention fairly high antibiotic resistance data. Adapted methods for following-up bacterial resistance evolution in general practice are needed.

Acute Disease↗

PubMed1990

[Development of resistance to antibiotic therapy at a polyvalent intensive care unit during 3 years].

The antibiotherapy resistance evolution and the appearance of new enterobacter in our ICU's flora have been studied. A total of 638 bacterial samples were studied. The most frequent isolated pathogens were: Pseudomonas aeruginosa (182 strands), Escherichia coli (108 strands), Staphylococcus epidermidis (99 strands) and Staphylococcus aureus (41 strands). These four types of bacteria have been used to evaluate the antibiotic resistance variations over a period of time, which have only been significant for Pseudomonas with an increased number of amikamicine's resistant strands after the second year (p less than 0.001) and the of one multiresistant strand to piperaciline and amikamicine this second year, and four (8%) the year after. There are not significant differences in the resistance of E. Coli, Staphylococcus aureus and Staphylococcus epidermidis over this period of time. We have not observed new enterobacter strands over the time this study was performed although a higher incidence of Serratia (p less than 0.05) and Enterobacter (p less than 0.05) have been detected between the first and the third year, respectively.

Bacterial Infections↗

PubMed2003

Estimated frequency of nonrecessive Bt resistance genes in bollworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) in eastern North Carolina.

In summer 2000, adult female bollworm moths, Helicoverpa zea (Boddie), were collected from light-traps at four locations near the Tidewater Research Station, Plymouth, NC. Female moths were allowed to lay eggs, and at hatch, 72 larvae from each female were screened for growth rate on normal artificial diet and on diets containing 5.0 microg of either Cry1Ac or Cry2Aa Bt toxin per milliliter of diet. The growth rate bioassays were performed to isolate nonrecessive Bt resistance genes present in field populations of bollworm. We found one individual out of 583 screened that appeared to carry a major gene for resistance to Cry1Ac. Assuming four alleles per individual, the gene frequency is 1/2332 or 0.0003. Other females appeared to have minor genes for Cry1Ac resistance or major genes with lower levels of dominance. We also found one individual out of 646 screened that appeared to carry a major gene for resistance to Cry2Aa. The gene frequency for Cry2Aa resistance was estimated at 1/2584 or 0.00039. Again, other females seemed to carry additional minor resistance genes. Along with other results that indicate partially dominant inheritance of Cry1Ac resistance in bollworm, these allele frequency estimates are important for determining the rate of resistance evolution in H. zea to specific Bt toxins.

Animals↗

PubMed2004

Delaying evolution of insect resistance to transgenic crops by decreasing dominance and heritability.

The refuge strategy is used widely for delaying evolution of insect resistance to transgenic crops that produce Bacillus thuringiensis (Bt) toxins. Farmers grow refuges of host plants that do not produce Bt toxins to promote survival of susceptible pests. Many modelling studies predict that refuges will delay resistance longest if alleles conferring resistance are rare, most resistant adults mate with susceptible adults, and Bt plants have sufficiently high toxin concentration to kill heterozygous progeny from such matings. In contrast, based on their model of the cotton pest Heliothis virescens, Vacher et al. (Journal of Evolutionary Biology, 16, 2003, 378) concluded that low rather than high toxin doses would delay resistance most effectively. We demonstrate here that their conclusion arises from invalid assumptions about larval concentration-mortality responses and dominance of resistance. Incorporation of bioassay data from H. virescens and another key cotton pest (Pectinophora gossypiella) into a population genetic model shows that toxin concentrations high enough to kill all or nearly all heterozygotes should delay resistance longer than lower concentrations.

Animals↗

PubMed1998

[Antibiotic sensitivity of Bacteroides fragilis group in Algeria].

The antimicrobial resistance evolution of the Bacteroïdes fragilis group is the subject of international survey. Eighty-six clinical isolates collected in anaerobic service of I.P. A were tested for susceptibility to twelve antimicrobial agents. Chloramphenicol, metronidazole and imipenem proved to be the most active agents. After these agents, amoxicillin-clavulanic acid, carbenicillin and piperacillin were the most effective agents tested with respectively 15%, 17% and 17% of resistant isolates. Clindamicin and cefotaxin were active from only 70% and 65% of clinical isolates, and 71% of them were found resistant to cefotaxin with minimal inhibitory concentration above 32 ug/ml. beta Lactamasic profile determination according to Rolfe and Finegold modified method allowed to show five different beta lactamase types. The isoelectric points (pI) vary between 4.3 and 7.5 according to the enzymatic extracts of the clinical isolates. No transfer and no plasmid were observed with respectively imipenem and metronidazole resistant isolates. But, transconjugants were obtained with TRCcR isolate.

Algeria↗

PubMed2006

Frequency of resistance to Bacillus thuringiensis toxin Cry1Ab in southern United States Corn Belt population of European corn borer (Lepidoptera: Crambidae).

The high-dose refuge resistance management strategy is the main approach used to delay resistance in targeted pests to Bacillus thuringiensis (Bt) toxins in transgenic crops. We used an F2 screen to test a critical assumption of the high-dose refuge strategy, which is that resistance allele (R) frequencies are initially rare (<10(-3)) in Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) from the southern Corn Belt. We expanded the methodological scope of the F2 screen so that both males and females may be used to initiate a screen and determined how the results from both sexes may be combined. In total, 62 female and 131 male O. nubilalis lines from Kansas and 39 female and four male lines from Texas were screened. No major resistance alleles were found and estimated R frequency for the southern Corn Belt was updated to between 0 and 0.0044 with 95% credibility. The experiment-wise detection probability was 98.7%. These results suggest the frequency of resistance alleles is low enough that the high-dose refuge resistance management strategy may be effective for delaying resistance evolution in O. nubilalis to Bt corn in the southern Corn Belt.

Animals↗

PubMed1997

Initial frequency of alleles for resistance to Bacillus thuringiensis toxins in field populations of Heliothis virescens.

The risk of rapid pest adaptation to an insecticide is highly dependent on the initial frequency of resistance alleles in field populations. Because we have lacked empirical estimates of these frequencies, population-genetic models of resistance evolution have relied on a wide range of theoretical estimates. The recent commercialization of genetically engineered cotton that constitutively produces an insecticidal protein derived from the biocontrol agent, Bacillus thuringiensis (Bt) has raised concern that we lack data needed to quantify the risk of insect pests such as Heliothis virescens rapidly adapting to this ecologically valuable class of toxins. By individually mating over 2,000 male H. virescens moths collected in four states to females of a Bt toxin-resistant laboratory strain, and screening F1 and F2 offspring for tolerance of the toxic protein, we were able to directly estimate the field frequency of alleles for resistance as 1.5 x 10(-3). This high initial frequency underscores the need for caution in deploying transgenic cotton to control insect pests. Our single-pair mating technique greatly increases the efficiency of detecting recessive resistance alleles. Because alleles that decrease target site sensitivity to Bt toxins and other insecticides are often recessive, this technique could be useful in estimating resistance allele frequencies in other insects exposed to transgenic insecticidal crops or conventional insecticides.

Journal Article↗

PubMed2000

Scaling and universality in electrical failure of thin films

We describe the electrical failure of thin films as a percolation in two-dimensional random resistor networks. We show that the resistance evolution follows a scaling relation expressed as R approximately epsilon(-&mgr;) where epsilon = (1-t/tau), tau is the time of electrical failure of the film, and &mgr; is the same critical exponent appearing in the scaling relation between R and the defect concentration. For uniform degradation the value of &mgr; is universal. The validity of this scaling relation in the case of nonuniform degradation is proved by discussing the case in which the failure is due to a filamentary defect growth. The existence of this relation allows predictions of failure times from early time measurements of the resistance.

Journal Article↗

PubMed2004

Monitoring western corn rootworm (Coleoptera: Chrysomelidae) susceptibility to carbaryl and cucurbitacin baits in the areawide management pilot program.

Areawide pest management involves the uniform application of a pest control strategy over wide geographic areas. Therefore, these programs are likely to impose intense selective pressures, and the risk for resistance development among pest species for which areawide management programs are implemented is likely to be high. Pilot studies for areawide management of western corn rootworm, Diabrotica virgifera virgifera LeConte, were conducted from 1996 to 2002 at four different sites across the Corn Belt. This program used cucurbitacin baits to deliver high doses of a traditional neurotoxic insecticide (carbaryl) to individual insects while reducing the overall rate of insecticide use. Because of the concern and potential for resistance evolution, annual assessments of susceptibility to the active ingredient carbaryl were conducted both within the managed area as well as from untreated control areas. Significantly reduced susceptibility to carbaryl based on survival at a diagnostic concentration was detected in three of the four management sites (Kansas, Iowa, and Illinois/Indiana), whereas susceptibility of beetles collected outside the managed areas remained unchanged. Additionally, significantly reduced responsiveness to cucurbitacin baits was observed in beetles collected from the managed area relative to the control area at the same three sites. These results suggest strongly that areawide management has the potential to select for resistance and that a strategy for managing resistance and reducing selective pressure should be proactively implemented.

Animals↗

PubMedDate not supplied

[Streptococcus pneumoniae: evolution of antibiotic resistance in a pediatric hospital in Córdoba, Argentina].

The wide variety of prevalence of antimicrobial resistant Streptococcus pneumoniae in different countries confirms the importance of determining local patterns of resistance. From 1992 to 2000, we studied the pattern of antimicrobial resistance in S. pneumoniae and its evolution along the years, using 468 strains isolated in the Hospital de Niños de Córdoba. A total of 177 isolates (37.8%) were not susceptible to penicillin, with 19% intermediate and 18.8% resistant strains. High and intermediate resistance levels to cefotaxime were 4.9% and 10.9%, respectively. Decreased susceptibility to trimethoprim/sulfamethoxazole (TMS), erythromycin, chloramphenicol, and rifampin was found in 194 isolates (41.5%), 32 (6.8%), 13 (2.8%) and 3 (0.6%), respectively. No isolates resistant to vancomycin were detected. The most commonly combined resistance patterns were: penicillin/TMS (35.6%) and penicillin/TMS/cefotaxime (11.8%). This study highlights the increased rate of drug resistant S. pneumoniae during the last years, and the importance of antimicrobial resistance surveillance of adequate empirical therapy involving local and regional susceptibility patterns.

Adolescent↗

PubMed2002

Evolution of herbicide resistance in weeds: initial frequency of target site-based resistance to acetolactate synthase-inhibiting herbicides in Lolium rigidum.

The frequency of individuals resistant to two acetolactate synthase (ALS)-inhibiting herbicides in three previously untreated populations of Lolium rigidum was determined. The frequency of individuals resistant to the sulfonylurea herbicide sulfometuron-methyl varied from 2.2 x 10(-5) to 1.2 x 10(-4) and the frequency of individuals resistant to the imidazolinone herbicide imazapyr varied from 1 x 10(-5) to 5.8 x 10(-5) depending on the population. Application of sulfometuron-methyl selected individuals with a herbicide-insensitive ALS, which was also cross-resistant to imazapyr. The high initial frequency of individuals resistant to ALS-inhibiting herbicides in L. rigidumpopulations never previously exposed to these herbicides helps explain the rapid evolution of herbicide resistance in this species once ALS-inhibiting herbicides were used.

Acetolactate Synthase↗

PubMed2005

Prevalence and penetrance variation of male-killing Wolbachia across Indo-Pacific populations of the butterfly Hypolimnas bolina.

Male-killing bacteria are generally thought to attain low to intermediate prevalence in natural populations, with only mild effects on the host population sex ratio. This view was recently challenged by reports of extremely high infection frequencies in three butterfly species, raising the prospect that male killers, by making males rare, might drive many features of host ecology and evolution. To assess this hypothesis, it is necessary to evaluate how often male killers actually produce a highly female-biased population sex ratio in nature, which requires both high prevalence of infection and high penetrance of action. To this end, we surveyed South Pacific and Southeast Asian populations of Hypolimnas bolina, a butterfly in which extreme prevalence of male-killing Wolbachia bacteria has recently been recorded. Our results indicate that highly female-biased populations are common in Polynesia, with 6 out of 12 populations studied having in excess of 70% of females infected with a fully efficient male killer. However, heterogeneity is extreme in Polynesia, with the male-killing Wolbachia absent from three populations. In contrast to the Polynesian situation, Wolbachia does not kill males in any of the three Southeast Asian populations studied, despite its very high prevalence there. We conclude that male killers are likely to have significant ongoing ecological and evolutionary impact in 6 of the 15 populations surveyed. The causes and consequences of the observed spatial variation are discussed with respect to host resistance evolution, host ecology and interference with additional symbionts.

Animals↗

PubMed2004

Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

INTRODUCTION: Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. METHODS: A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. RESULTS: After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. DISCUSSION: Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

Anti-HIV Agents↗

PubMed2001

The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones.

The key genetic component of methicillin resistance, the mecA determinant, is not native to Staphylococcus aureus. Thus, the evolution of methicillin-resistant S. aureus (MRSA) must have begun with the acquisition of the mecA determinant from an unknown heterologous source some time before the first reported appearance of MRSA isolates in clinical specimens in the U.K. and Denmark (in the early 1960s). We compared the genetic backgrounds and phenotypes of a group of methicillin-susceptible S. aureus (MSSA) isolates to the properties of MRSA strains isolated in Denmark and the U.K. during the same time period, and also to the genetic profiles of contemporary epidemic clones of MRSA. All early MRSA isolates resembled a large group of the early MSSA blood isolates in phenotypic and genetic properties, including phage group, antibiotype (resistance to penicillin, streptomycin, and tetracycline), pulsed-field gel electrophoresis pattern, and spaA type and multilocus sequence type, strongly suggesting that the early MSSA examined here represented the progeny of a strain that served as one of the first S. aureus recipients of the methicillin-resistance determinant in Europe. The genetic background of this group of early MSSA isolates was also very similar to that of the widely disseminated contemporary "Iberian clone" of MRSA, suggesting that genetic determinants present in early MSSA and essential for some aspects of the epidemicity and/or virulence of these strains may have been retained by this highly successful contemporary MRSA lineage.

Amino Acid Sequence↗