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PubMed1971

Puromycin resistance in haploid and heteroploid frog cells: gene or membrane determined?

The frequency of colony formation in monolayers of cultured frog cell lines treated with puromycin was compared in (a) haploid and heteroploid lines and (b) mutagen-treated and nontreated haploid lines. Evidence that resistant colonies result from gene mutation was negative, since the colony frequency is independent of both ploidy and mutagen treatment. A study of five frog cell lines showed that colony formation in puromycin depends on (a) the concentration of puromycin, (b) preselection of the population with puromycin, and, particularly, (c) the capacity of the treated population to survive some exposure to puromycin. One haploid and one heteroploid strain showing stable resistance to puromycin have been isolated; comparison of those variants with sensitive populations has shown that resistance to puromycin is correlated with the cells' capacity to exclude the drug. The evidence for different levels of membrane permeability, combined with evidence for many degrees of resistance among and within cell populations, suggests a model of self-determining membrane units. The evolution of a resistant phenotype may result from changes in the proportion of specific units in the membrane population.

Animals↗

PubMed1998

Resistance issues and treatment implications: pneumococcus, Staphylococcus aureus, and gram-negative rods.

During the last decade there has been an unexpectedly rapid evolution of antimicrobial resistance in the respiratory pathogens for community- and hospital-acquired pneumonia. In order to choose the most optimal therapy for their patients, it is essential that physicians be aware of the prevalence and mechanisms of resistance and their implications on the effectiveness of the various antimicrobials.

Anti-Bacterial Agents↗

PubMed2005

The antiretroviral rollout and drug-resistant HIV in Africa: insights from empirical data and theoretical models.

The U.S. Government has pledged to spend $15 billion in Africa and the Caribbean on AIDS. A central focus of this plan is to provide antiretroviral treatment (ART) to millions. Here, we evaluate whether the plan to rollout ART in Africa is likely to generate an epidemic of drug-resistant strains of HIV. We review what has occurred as a result of high usage of ART in developed countries in terms of changes in risky behavior, and the emergence and transmission of drug-resistant HIV. We also review how mathematical models have been used to predict the evolution of drug-resistant HIV epidemics. We then show how models can be used to predict the likely impact of the ART rollout on the evolution of drug-resistant HIV in Africa. At currently planned levels of treatment coverage, we predict that (over the next decade) in Africa: (i) the impact of ART on reducing HIV transmission (and prevalence) is likely to be undetectable (unless accompanied by substantial changes in behavior), (ii) the transmission rate of drug-resistant HIV will be below the WHO surveillance threshold of 5%, and (ii) the majority of cases of drug-resistant HIV that will occur will be due to acquired (and not transmitted) resistance. For the next decade, large-scale surveillance for detecting transmitted resistance in Africa is unnecessary. Instead, we recommend that patients should be closely monitored for acquired resistance, and sentinel surveillance (in a few urban centers) should be used to monitor transmitted resistance.

Africa↗

PubMed1995

Repetitive DNA sequences located in the central region of the human mdr1 (multidrug resistance) gene may account for a gene fusion event during its evolution.

The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA).poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent "molecular fossils" of ancient DNA elements which were involved in such a recombination event.

Base Sequence↗

PubMed2006

Multiple-stress tolerance of ionizing radiation-resistant bacterial isolates obtained from various habitats: correlation between stresses.

Isolation of five ionizing radiation (IR)-resistant bacteria by screening of isolates from various habitats classified as common and stressed is reported. IR-resistant isolates exhibited varying degrees of resistance to gamma-radiation and were classified as highly and moderately radiation resistant. Resistance to ultraviolet (UV) radiation correlated well with gamma-radiation resistance, whereas a comparable desiccation resistance for all the highly and moderately radiation-resistant isolates was observed. However, salt tolerance failed to correlate with IR resistance, indicating a divergent evolution of the salt tolerance and radiation resistance. Characterization of isolates by the amplified rDNA restriction analysis profiling attested to the clustering of these isolates with their stress phenotype. 16S rRNA gene-based analysis of the isolates showed that the bacteria with similar-resistance physiologies clustered together and belonged to related genera. Hydrogen peroxide resistance and mitomycin survival patterns of the isolates indicated the roles of oxidative-stress tolerance in desiccation survival and recombination repair in higher radiation resistance, respectively.

DNA, Bacterial↗

PubMed1994

Ten-year surveillance of drug-resistant malaria in Burkina Faso (1982-1991).

To understand the evolution of drug-resistant forms of malaria in time and in space, we carried out an analysis of the results of a series of passive and active surveys conducted in Burkina Faso between 1982 and 1991. A total of 607 tests for resistance to chloroquine and mefloquine were carried out in vitro and 3,679 tests for resistance to chloroquine, quinine, and sulfadoxine-pyrimethamine were performed in vivo. The surveys principally involved the two main cities of Burkina Faso, Ouagadougou and Bobo-Dioulasso. However, another 10 locations representing the three different zones of malaria transmission were also studied. The first cases of Plasmodium falciparum resistant to chloroquine in vitro were reported in 1983, but it was only in 1988 that in vivo resistance appeared. The first cases of in vitro resistance to mefloquine were noted in 1987 while chloroquine sensitivity at a high rate (15.8%), which decreased during the following years. The prevalence of resistance to chloroquine increased in parallel to this decrease in sensitivity to an overall peak of 41% in vitro and 16% in vivo in 1990. These rates then decreased to 3% and 6%, respectively, in 1991. This pattern of decreasing resistance was broadly similar in all sites except for the town of Bobo-Dioulasso, where the level of resistance remained stable at approximately 14% from 1988 to 1991. Only two cases of resistance in vivo to sulfadoxine-pyrimethamine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2003

Evolution of sporadic isolates of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and their similarities to isolates of community-acquired MRSA.

Forty-one methicillin-resistant Staphylococcus aureus (MRSA) hospital isolates that clearly differed from the six major pandemic clones of MRSA in pulsed-field gel electrophoresis type, mecA and Tn554 polymorphism, and epidemic behavior were selected from an international strain collection for more detailed characterization. SpaA typing, multilocus sequence typing, and SCCmec (staphylococcal cassette chromosome mec) typing demonstrated extensive diversity among these sporadic isolates both in genetic background and also in the structure of the associated SCCmec elements. Nevertheless, the isolates could be grouped into restricted clonal complexes by using the BURST (i.e., based upon related sequence types) program algorithm, which predicted that most sporadic MRSA isolates evolved from pandemic MRSA clones. Several of the sporadic MRSA resembled community-acquired MRSA isolates in properties that included a relatively limited multiresistance pattern, faster growth rates, diversity of genetic backgrounds, and a frequent association with SCCmec type IV.

Algorithms↗

PubMed2005

Herbicide-resistant crops and weed resistance to herbicides.

The adoption of genetically modified (GM) crops has increased dramatically during the last 3 years, and currently over 52 million hectares of GM crops are planted world-wide. Approximately 41 million hectares of GM crops planted are herbicide-resistant crops, which includes an estimated 33.3 million hectares of herbicide-resistant soybean. Herbicide-resistant maize, canola, cotton and soybean accounted for 77% of the GM crop hectares in 2001. However, sugarbeet, wheat, and as many as 14 other crops have transgenic herbicide-resistant cultivars that may be commercially available in the near future. There are many risks associated with the production of GM and herbicide-resistant crops, including problems with grain contamination, segregation and introgression of herbicide-resistant traits, marketplace acceptance and an increased reliance on herbicides for weed control. The latter issue is represented in the occurrence of weed population shifts, the evolution of herbicide-resistant weed populations and herbicide-resistant crops becoming volunteer weeds. Another issue is the ecological impact that simple weed management programs based on herbicide-resistant crops have on weed communities. Asiatic dayflower (Commelina cumminus L) common lambsquarters (Chenopodium album L) and wild buckwheat (Polygonum convolvulus L) are reported to be increasing in prominence in some agroecosystems due to the simple and significant selection pressure brought to bear by herbicide-resistant crops and the concomitant use of the herbicide. Finally, evolution of herbicide-resistant weed populations attributable to the herbicide-resistant crop/herbicide program has been observed. Examples of herbicide-resistant weeds include populations of horseweed (Conyza canadensis (L) Cronq) resistant to N-(phosphonomethyl)glycine (glyphosate). An important question is whether or not these problems represent significant economic issues for future agriculture.

Adaptation, Physiological↗

PubMed1989

[Drug-resistance and its transferability of Shigella strains isolated in 1986 in Japan].

Two hundred and fifty Shigella strains isolated in Japan were examined for their drug-resistances and their conjugal transferability. Drugs used and the isolation frequency of resistant strains were: sulfanilamide (SA) 96%, streptomycin (SM) 85%, tetracycline (TC) 82%, fosfomycin (FOM) 76%, chloramphenicol (CP) 51%, trimethoprim (TMP) 46%, ampicillin (ABPC) 45%, nalidixic acid (NA) 6%, kanamycin (KM) 5%, cephaloridine (CER) 4%, gentamicin (GM) 0%, amikacin (AMK) 0%, colistin (CL) 0%, norfloxacin (NFLX) 0%. All of the KM-resistances and none of the FOM-resistances were transferable. Each 20 to 30% of CP, TC, SM, SA or ABPC-resistant isolates transferred each drug-resistance. Two thirds of the isolates were brought to Japan by travellers mostly from South-East Asia. The isolation frequency of resistant strains was not different between domestic and foreign strains except that NA-resistance was not found in foreign strains. The frequency of isolates carrying transferable R plasmids were higher in domestic strains than foreign strains. Most of the isolated had multiple drug-resistance. Major resistance types were: (CP, TC, SM, SA, ABPC) 22%; (TC, SM, SA, TMP) 20%; (CP, TC, SM, SA, ABPC, TMP) 16%; (TC, SM, SA) 8%. Strains showing different resistance types were different among each other in their serum type, conjugal transferability, and derived country. Stepwise evolution of multiple resistance in one country was not demonstrated. The resistance types of Shigella isolates in Japan have been influenced by yearly change of imported strains.

Anti-Bacterial Agents↗

PubMed2002

The evolution of beta-cell dysfunction and insulin resistance in type 2 diabetes.

Insulin resistance and beta-cell dysfunction have important roles in the pathogenesis and evolution of type 2 diabetes. The development of precise methods to measure these factors has helped us to define the relationship between them and evidence is reviewed that changes in insulin sensitivity are compensated by inverse changes in beta-cell responsiveness such that the product of insulin sensitivity and insulin secretion (the disposition index) remains constant. While the disposition index promises to be a useful tool to predict individuals at high risk of developing type 2 diabetes, other factors that contribute to beta-cell dysfunction and mark disease onset and progression include impairments in proinsulin processing and insulin secretion, decreased beta-cell mass and islet amyloid deposition. Emerging data indicate that anti-diabetic agents, such as the thiazolidinediones that simultaneously target insulin resistance and beta-cell dysfunction, may have a beneficial impact on disease onset and progression. Several landmark clinical studies are underway to investigate if their initial promise is supported by data from large-scale trials.

Amyloid↗

PubMed2006

Serotype distribution and antimicrobial resistance of Salmonella enterica from patients with gastroenteritis in Crete, Greece.

The aim of the present study was to determine the serotype distribution and the evolution of antimicrobial resistance among Salmonella enterica strains isolated from patients with diarrhea in Crete, Greece, during a 5-year period (2000-2004). Among the 401 S. enterica isolates recovered, serotype Enteritidis was the most prevalent (66.6%), followed by serotype Typhimurium (14.2%). The rates of resistance to ampicillin, amoxicillin-clavulanic acid, gentamicin, chloramphenicol, tetracycline, nalidixic acid and trimethoprim-sulfamethoxazole were 8.5, 7, 0.7, 5.4, 14.2, 2.7 and 2.7%, respectively. A marked decrease in resistance was observed during the study period. Resistance and multidrug resistance was most common in serotype Typhimurium. The extended-spectrum beta-lactamase production observed in one strain of S. enterica serotype Virchow and the reduced ciprofloxacin susceptibility detected in 2.7% of the isolates studied are causes of concern.

Drug Resistance, Bacterial↗

PubMedDate not supplied

Increasing prevalence of ampicillin- resistant, non-beta-lactamase-producing strains of Haemophilus influenzae in children in Japan.

Among Haemophilus influenzae isolated from children with respiratory tract infections, the evolution of ampicillin resistance was investigated during 1996 and 1997 in Japan. beta-Lactamase production was assessed and minimum inhibitory concentrations (MICs) of eight antimicrobial agents were determined using a broth microdilution method in Mueller-Hinton-lysed horse blood medium. Of 74 H. influenzae, 11 strains (14.9%) produce beta-lactamase and were thus highly resistant to ampicillin (MIC of >4.0 microgram/ ml). In addition, moderate resistance to ampicillin, defined as an MIC of >==1.0 microgram/ml, was noted in 44.4% of all beta-lactamase-negative isolates. These beta-lactamase-negative ampicillin-resistant (BLNAR) organisms were resistant to other cephalosporins such as cefpodoxime and cefdinir, while beta-lactamase-producing strains were susceptible to them. Cefditoren, cefteram, and minocycline were active against all strains studied, whereas cefaclor and clarithromycin were inactive against all H. influenzae isolates in this study. Results indicate that BLNAR strains have emerged among children with respiratory tract infections in Japan.

Ampicillin↗

PubMed1994

Drug resistance and its counteraction by cyclosporin A in function of metastatic potential in the Lewis lung carcinoma system.

Tumor progression (TP) is often accompanied by evolution of drug resistant clones. Decreased intracellular accumulation of cytotoxic agents is probably the major mechanism of drug resistance. In the present study, we tried to examine the possibility to overcome the resistance to adriamycin (ADR) treatment, by cyclosporin A (CS) in two models of TP in the Lewis lung carcinoma (3LL) system. The first model consisted in the comparison of primary tumor cells (3LL-PT) to metastatic cells (3LL-MT) and the second consisted in comparison of lung metastases of the highly malignant variant D122 to those of the parental 3LL tumor. Cyclosporin had a weak augmenting effect on ADR uptake, in the two more malignant cell variants and no influence on the 3LL-PT cells, according to FACS analysis. Cytofluorometry also showed practically no effect of CS on cell size, unlike the effect of other chemosensitizers, such as membrane active agents. In order to find out whether CS counteracts resistance to ADR despite the fact that it does not increase cytotoxic agent uptake, we examined its effect on in vitro proliferative capacity of the 3LL-PT cells. CS in combination with ADR had a more pronounced effect, as compared to single treatments on cell proliferation. The low effect of CS on ADR uptake according to FACS analysis, and by contrast, its efficiency to overcome resistance to ADR according to the in vitro growth results, suggest that the mechanism of the CS action as a chemosensitizer is not related to the p-glycoprotein (P-G-P), known to be overexpressed in the typical multidrug-resistance (MDR) phenotype. A better understanding of the complexity of MDR mechanisms may contribute to the design of new modalities to overcome this phenomenon, which still limits effectiveness of cancer cure, to the early stages of the disease.

Animals↗

PubMed2004

Evolutionary change from induced to constitutive expression of an indirect plant resistance.

Induced plant resistance traits are expressed in response to attack and occur throughout the plant kingdom. Despite their general occurrence, the evolution of such resistances has rarely been investigated. Here we report that extrafloral nectar, a usually inducible trait, is constitutively secreted by Central American Acacia species that are obligately inhabited by ants. Extrafloral nectar is secreted as an indirect resistance, attracting ants that defend plants against herbivores. Leaf damage induces extrafloral nectar secretion in several plant species; among these are various Acacia species and other Fabaceae investigated here. In contrast, Acacia species obligately inhabited by symbiotic ants nourish these ants by secreting extrafloral nectar constitutively at high rates that are not affected by leaf damage. The phylogeny of the genus Acacia and closely related genera indicate that the inducibility of extrafloral nectar is the plesiomorphic or 'original' state, whereas the constitutive extrafloral nectar flow is derived within Acacia. A constitutive resistance trait has evolved from an inducible one, obviously in response to particular functional demands.

Acacia↗

PubMed1993

Cloning and sequencing of the cyclodiene insecticide resistance gene from the yellow fever mosquito Aedes aegypti. Conservation of the gene and resistance associated mutation with Drosophila.

In order to examine the conservation of the mechanism of cyclodiene insecticide resistance between species we cloned a cDNA from the yellow fever mosquito Aedes aegypti homologous to the resistance gene Rdl in Drosophila. In D. melanogaster, resistance to cyclodienes and picrotoxinin is caused by a single amino acid substitution (alanine to serine) in the putative channel lining of a gamma-aminobutyic acid gated chloride ion channel. We report that the mosquito gene not only shows high homology to that of Drosophila but also that resistant strains display substitution of the same amino acid. The significance of this result in relation to the evolution of pesticide resistance, the use of Drosophila as a model insect for resistance studies and the potential use of this gene as a selectable marker in the genetic transformation of non-Drosophilids is discussed.

Aedes↗

PubMed2025

Chromosomal resistance mutations facilitate acquisition of multidrug-resistant plasmids in Escherichia coli.

Bacteria can gain multiple resistance mechanisms in a single step by the acquisition of multidrug-resistant (MDR) plasmids, but it is unclear how antibiotic selection during the acquisition of MDR plasmids affects the evolution of additional resistance mechanisms. Through conjugating separate extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing MDR plasmids into plasmid-naive Escherichia coli hosts, we examine the effects of acquisition of a single plasmid or co-acquisition of multiple plasmids upon fitness costs, resistance and subsequent genomic adaptation. We show that acquisition of pOXA-48, encoding OXA-48 carbapenemase, is associated with highly variable fitness costs and levels of resistance to ertapenem in transconjugants independent of the presence of pLL35. This phenomenon was not observed during the acquisition of ESBL CTX-M-15-encoding pLL35 alone. Within a single growth cycle, transconjugants receiving pOXA-48 rapidly gained parallel mutations affecting the membrane porin OmpF, or its regulators OmpR or EnvZ. These chromosomal mutations were not compensatory for the fitness costs imposed by the plasmid, nor did they provide significant increases in resistance to carbapenems in the absence of the pOXA-48. Rather, they acted synergistically with the plasmid-encoded carbapenemase, which alone only provided marginal resistance, together providing high-level resistance to ertapenem. Such rapid evolutionary processes may play an important role in plasmid dynamics within environments with strong antibiotic selection for plasmid-encoded antimicrobial resistance genes (ARGs), particularly when these ARGs provide only marginal resistance.

Escherichia coli↗

PubMed2006

Presence of new mecA and mph(C) variants conferring antibiotic resistance in Staphylococcus spp. isolated from the skin of horses before and after clinic admission.

Because of the frequency of multiple antibiotic resistance, Staphylococcus species often represent a challenge in incisional infections of horses undergoing colic surgery. To investigate the evolution of antibiotic resistance patterns before and after preventative peri- and postoperative penicillin treatment, staphylococci were isolated from skin and wound samples at different times during hospitalization. Most staphylococci were normal skin commensals and belonged to the common coagulase-negative group. In some cases they turned out to be opportunistic pathogens present in wound infections. MICs were determined for 12 antibiotics, and antibiotic resistance genes were detected by microarray. At hospital admission, horses harbored staphylococci that were susceptible to antibiotics or resistant to one group of drugs, mainly due to the presence of new variants of the methicillin and macrolide resistance genes mecA and mph(C), respectively. After 3 days, the percentage of Staphylococcus isolates displaying antibiotic resistance, as well as the number of resistance genes per isolate, increased moderately in hospitalized horses without surgery or penicillin treatment but dramatically in hospitalized horses after colic surgery as well as penicillin treatment. Staphylococcus species displaying multiple resistance were found to harbor mainly genes conferring resistance to beta-lactams (mecA and blaZ), aminoglycosides [str and aac(6')-Ie-aph(2')-Ia], and trimethoprim [dfr(A) and dfr(D)]. Additional genes conferring resistance to macrolides [mph(C), erm(C), and erm(B)], tetracycline [tet(K) and tet(M)], chloramphenicol [cat(pC221) and cat(pC223)], and streptothricin (sat4) appeared in several strains. Hospitalization and preventive penicillin use were shown to act as selection agents for multidrug-resistant commensal staphylococcal flora.

Animals↗

PubMed1995

Falciparum malaria, imported into The Netherlands, 1979-1988. I. Epidemiological aspects.

From 1979-1988, 427 patients with falciparum malaria were prospectively investigated for chloroquine resistance. About 90% were infected in sub-Saharan Africa. Of the 361 non-immune patients 235 were evaluable; in 158 (67%) chloroquine resistance of Plasmodium falciparum could be confirmed. Chloroquine sensitivity was found in 77 (32%) patients. Sulfadoxine-pyrimethamine resistance was found in 33 patients. The history of use of chemoprophylaxis was recorded in 357 patients: 168 (49%) took adequate, 103 inadequate and 86 no chemoprophylaxis. In 65 of the 168 patients with a history of good compliance, prophylactic serum concentrations could be measured; in 56 (86%) patients the history was confirmed by the chloroquine level. All but one of them were infected with a resistant P. falciparum strain. Of the 66 semi-immune patients, 60 were infected in their homeland; in 5 (8%) chloroquine resistance was found. Only 1 of the 60 patients had used adequate chemoprophylaxis and proved to be infected with a resistant P. falciparum strain. During the study the spread of drug resistance from East Africa to other parts of Africa could be observed. Monitoring for drug-resistant falciparum malaria in travellers returning from malaria-endemic areas is a helpful tool in predicting the evolution of drug resistance in that area. In the non-endemic area such monitoring is essential for optimal advice on treatment of patients and of chemoprophylaxis in travellers.

Adolescent↗