Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “resistant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1999

[Antimicrobial resistance in Streptococcus pneumoniae in Beijing and molecular typing of penicillin-resistant strains].

OBJECTIVE: To investigate antimicrobial resistance of Streptococcus pneumoniae in Beijing and molecular epidemiology of penicillin-resistant pneumococci strains. METHODS: The resistance to beta-lactam and non-beta-lactam antibiotics of 244 nasopharyngeal isolates of Streptococcus pneumoniae collected from September to November 1997 in 8 day-care centers in Beijing was studied by Etest and agar dilution method. Serotyping was done by "capsular swelling" technique. BOX-PCR technique was used to detect the DNA of resistant strains. RESULTS: 24.8% (244/985) of the children carried Streptococcus pneumoniae. The agreement between the MICs obtained by Etest and agar dilution for penicillin and ceftriaxone was > 93.7%. By Etest, 3/244 (1.3%) strains were resistant to penicillin(MICs, 3 micrograms/ml) and 32/244(13.1%) strains in termedinte (MICs, 0.094-0.25 microgram/ml). Penicillin-susceptible strains were also susceptible to the other 4 tested beta-lactams. In penicillin non-susceptible strains, 11.4% (4/35) isolates were resistant to the other beta-lactams. The resistant rates of erythromycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole (TMP-SMZ) were 74.0%, 87.6%, 47.8%, 63.3%, respectively. All of the strains were susceptible to vancomycin and rifampin. 119/244(48.7%) strains isolated were multiresistant to tetracycline, erythromycin and TMP/SMZ. Serotype 6A(33.6%), 19F(16.8%), 23F(15.1%), 15(11.2%), 6B(4.3%) were most common. 57.1% (20/35) penicillin non-susceptible strains were of serotype 23F and had similar or identical multiresistance and BOX patterns. CONCLUSION: In Beijing, the prevalence of penicillin-resistant pneumococci was obviously lower than that of neighboring countries, but resistant rate to non-beta-lactams was high. The epidemic multiresistant 23F clone found in day-care centers was different from the Spanish clone.

Anti-Bacterial Agents↗
PubMed2001

[Correlation between methicillin-resistance and resistance to fluoroquinolones in Staphylococcus aureus and Staphylococcus epidermidis].

Fluoroquinolones resistance in Staphylococci is associated to point mutations in grlA (80,84 and 116) grlB, gyrA (84,88) and gyrB genes. Almost all MRSA strains are ciprofloxacin and levofloxacin resistant while, in a lesser degree, MRCoN staphylococci show to be resistant to levofloxacin. This observation made possible to predict a different correlation between methicillin-resistance and the resistance to FQs in this two different species. In this study, we compare genomic analysis of S. aureus and S. epidermidis with the resistance to FQs. Our results show that strains of MRSA are distributed in 4 different PFGE-types while 12 MRSE strains are distributed in 9. MRSA resistant to FQs showed a unique PFGE pattern; on the contrary of FQs susceptible MRSA and MSSA. Furthermore mecA and gyrA genes are located in the same SmaI fragment in MRSA and in different in MRSE. MSSE and MRSE show more ClaI/mecA polymorphisms than MRSA. All this data confirm the clonal origin of MRSA and show that FQs resistance is linked to the presence of mec locus and both clonally spread. On the contrary in MRSE FQs-resistance is independent from MR and arise with the normal frequence of antibiotic induction.

Anti-Infective Agents↗
PubMed1992

[Aminoglycosides resistance of methicillin-resistant Staphylococcus aureus].

In the last decade, there has been a dramatic increase in the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) in Japan. Especially, a high incidence of multiple resistant MRSA strains has been reported. These strains are resistant not only to beta-lactams but to aminoglycosides and macrolides. About 90% of MRSA strains were resistant to gentamicin (GM) and/or tobramycin (TOB), producing an aminoglycoside modifying enzyme, mainly, APH (2")/AAC (6) and/or AAD (4',4"). Based on these modifying enzymes produced, MRSA strains were classified into three groups; group 1 produced APH (2")/AAC (6), belonging to phage group I and coagulase IV, group 2 produced AAD (4',4"), belonging to phage group III and coagulase II, and group 3 produced APH (2")/AAC (6) and AAD (4',4"), belonging to phage group III and coagulase II. The epidemiological results suggest that MRSA strains changed from group 1 to group 2, and then to group 3. Recently, arbekacin (ABK), a new anti-MRSA aminoglycoside, has been introduced into clinical practice. ABK shows a potent activity to GM-resistant strains, due to poorly modification by APH (2")/AAC (6'). However, there were few ABK- and GM-resistant strains in clinical isolates. These strains produced a higher amount of the enzyme than ABK-susceptible and GM-resistant strains. This observation suggests that ABK-resistant strains might be derived from GM-resistant strains by mutation of the gene coding APH (2")/AAC (6').

Acetyltransferases↗
PubMed1979

Vertical gradient in regional vascular resistance and pre to post capillary resistance ratios in the dog lung.

The ratios of pre-capillary (Ra) and post-capillary (Rv) resistances to total vascular resistance (RT) were measured at different vertical distances in the lungs of supine dogs. Capillary pressures were estimated as the algebraic sum of the alveolar absorption pressure for Tyrode's solution and the plasma colloid osmotic pressure. Segmental resistance fractions (Ra/RT, Rv/RT) were calculated using the pressure drops between arterial, capillary, and venous pressures at each vertical distance within the lung. In a second group of animals, total vascular resistance was calculated at each lung level using regional blood flow as measured by radiolabelled microspheres and the corresponding regional vascular pressures. The total vascular resistance was lowest in Zone III portions of the lung, but Ra/RT and Rv/RT were constant throughout this zone (n = 22) averaging .63 +/- .02 (SEM) and .37 +/- .02 (SEM, respectively, resulting in Ra/Rv of 1.70). Total vascular resistance increased markedly in Zone II portions of the lung, but the relative contribution of Ra/RT decreased from .62 +/- .07 (SEM) to .45 +/- .05 (SEM). Thus Ra/Rv decreased from 1.70 to .82 in Zone II. The absolute values of pre- and post-capillary resistances were lowest in Zone III but post-capillary resistance increased to a greater degree than pre-capillary resistance up Zone II.

Animals↗
PubMed1994

[Emergence of arbekacin resistant strains among methicillin-resistant Staphylococcus aureus].

We studied the efficacy of arbekacin (ABK) against MRSA that were resistant to gentamicin (GM). ABK was fairly active against most of the GM-resistant MRSA strains. Against highly GM-resistant strains, however, ABK was slightly less active than it was against the low level GM-resistant strains. ABK-resistant mutants were isolated from GM-resistant MRSA at a frequency of 10(-4) to 10(-5) when the selection was made with MIC of ABK. But the frequency decreased with higher concentration of ABK or with a use of 1/2 MIC of beta-lactam antibiotics, such as cefazolin, cefotiam, cefamandole or flomoxef, together with ABK. We isolated a ABK-resistant mutant from a laboratory strain MS353/pMS91 which possess a GM-resistant gene on a plasmid. The gene encodes a modifying enzyme, AAC-6'/APH-2". We compared the enzyme activities between the mutant MS353/pMS91M and MS353/pMS91. The mutant strain showed enzyme activity six times as much as the primary strain. This result suggests that the increase of AGs-modifying enzymes was responsible for the ABK-resistance of MRSA.

Acetyltransferases↗
PubMed1998

Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins.

Cross-resistance to a wide array of toxic chemicals is a common phenomenon in cisplatin-resistant cell lines. In this study, two independently isolated cisplatin-resistant cell lines derived from a human hepatoma and a cervical adenocarcinoma were shown to be cross-resistant to methotrexate (MTX) and several metal salts, such as sodium arsenite, sodium arsenate, antimony potassium tartrate, and cadmium chloride. A pleiotropic defect resulting in reduced accumulation of cisplatin, 3[H]MTX, 73As3+, and 73As5+ was found in both cisplatin-resistant cell lines. Analysis by immunoblot, indirect immunofluorescence, and Northern hybridization showed dramatically reduced expression of the folate binding protein that mediates MTX uptake in both human cisplatin-resistant cell lines. By photoaffinity labeling with UV irradiation, specific binding proteins of Mr 230,000 and Mr 48,000 for 73As3+ and Mr 190,000 for 73As5+ were found in enriched plasma membrane of both human cisplatin-sensitive parental cell lines. Expression of these specific binding proteins was decreased in cells selected for cisplatin resistance. A protein band at Mr 36,000 that binds to 73As3+ was overexpressed in both human cisplatin-resistant cell lines. The finding of loss of distinct binding proteins for MTX, arsenate, and arsenite in association with decreased accumulation of these agents in cisplatin-resistant cells suggests a pleiotropic, possibly regulatory, alteration in these cells.

Antineoplastic Agents↗
PubMed1997

Establishment of doxorubicin-resistant human bladder cancer cell line (BUI-87/ADMR) and its mechanism of multidrug resistance.

OBJECTIVE: To establish a doxorubicin-resistant human bladder cancer cell line, BIU-87/ADMR, and to study its biological characteristics and mechanism of drug resistance. METHODS: A human bladder cancer cell line resistant to doxorubicin, BIU-87/ADMR, has been established in vitro by exposing BIU-87 parent cells to progressively increasing concentrations of the drug over a period of 8 months. The cell line has been characterized in terms of growth kinetics, morphology, cross-resistance to other anticancerous agents, pharmacokinetics of daunorubicin and expression of P-glycoprotein (P-gp) which is closely related to the MDR phenotype. RESULTS: The BIU-87/ADMR cell line was 6.3 times more resistant to doxorubicin than the parent BIU-87. It exhibited cross-resistance to doxorubicin derivatives (epirubicin, daunorubicin), vincristine and etoposide, but not to cisplatin and mitomycin C. Compared to the parent cells, the resistant cells have a slower growth rate and lower confluent density. Unlike the parent BIU-87, about 75% of the BIU-87/ADMR cells showed a positive reaction with monoclonal antibody against P-gp, JSB-1. Intracellular drug accumulation studies with fluorescence spectrometry indicated that the resistance exhibited by the BIU-87/ ADMR line was mainly caused by an increased active efflux. CONCLUSIONS: The results suggest that MDR is an important phenomenon in bladder cancer and that more than one pathway of MDR may be present in human bladder cancer cell lines. BIU-87/ADMR may be a useful model for the development of new chemotherapeutic strategies in overcoming drug-resistance in the treatment of bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Impairment of Fas-antigen expression in adriamycin-resistant but not TNF-resistant MCF7 tumor cells.

Anti-cancer drugs and cytotoxic cytokines such as members of the TNF/Fas-ligand family play a predominant role in apoptosis induction in tumor cells, and are critical in cancer therapy. In this study we used the human breast-carcinoma cell line MCF7, its derivatives MCF7Adr (resistant to adriamycin) and R-A1 (resistant to TNF), to determine the impact of acquired drug and cytokine resistance on susceptibility to Fas-induced cytotoxicity and Fas-antigen expression. While MCF7 and R-A1 cells were killed by anti-Fas in the presence of IFN-gamma, MCF7Adr was found to be resistant to Fas-mediated apoptosis. This resistance was correlated with a loss of surface Fas-protein expression. Fas-gene transfer in MCF7Adr resulted in high sensitivity to Fas-mediated cytotoxicity, indicating that the Fas signalling pathway is virtually intact in this cell line. Over-expression of the MDR1 gene in MCF7 following gene transfer did not affect Fas expression and anti-Fas sensitivity, suggesting that the P-gp-mediated multidrug-resistance phenotype is not directly involved in the loss of Fas expression, contrary to what has been observed by others in T-cell lines. Furthermore, the down-regulation of Fas expression and subsequent resistance to anti-Fas were observed in drug-resistant human ovarian-carcinoma IGR-OV1/VCR cells and leukemic lymphoblast CEM/VLB cells, suggesting that the alteration of Fas expression following drug-resistance selection is not restricted to one cell type.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Topiramate for drug-resistant partial epilepsy.

BACKGROUND: The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of topiramate when used as an add-on treatment in patients with drug resistant partial epilepsy. SEARCH STRATEGY: (a) The Cochrane Library (1999 Issue 1); (b) The controlled trial register of the Cochrane Epilepsy Group; (c) Johnson and Johnson, makers of topiramate; (d) Experts in the field. SELECTION CRITERIA: Randomized placebo controlled add-on trials of topiramate in patients with drug resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Summary odds ratios (OR) were estimated for each outcome. Dose response was evaluated in regression models. MAIN RESULTS: Six trials were included representing 743 randomized patients. EFFICACY: Overall OR (95% CIs) for 50% or greater reduction in seizure frequency compared to placebo 4.06 (2.86-5.78). Dose regression analysis shows increasing efficacy with increasing dose, but found no advantage for doses over 400 mg per day. Global effectiveness: treatment withdrawal OR (95% CIs) compared to placebo 2.57 (1.65-4.00). Side effects: OR (99% CIs)compared to placebo, dizziness 1.99 (1.20-3.29); fatigue 2.52 (1. 47-4.32); nausea 2.84 (1.36-5.93); somnolence 2.89 (1.72-4.85) and 'thinking abnormally' 3.71 (2.02-6.80) were significantly associated with topiramate. REVIEWER'S CONCLUSIONS: Topiramate has efficacy as an add-on treatment in patients with drug resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of topiramate. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.

Anticonvulsants↗
PubMed2003

Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants.

Breast cancer resistance protein (BCRP) is a member of ATP-binding cassette transporters that has an N-terminal ATP binding domain and a C-terminal transmembrane domain (TM). Expression of wild-type BCRP confers resistance to multiple chemotherapeutic agents such as mitoxantrone, SN-38 and topotecan, but not to doxorubicin. We made 32 BCRP mutants with an amino acid substitution in the TMs (7 E446-mutants in TM2, 15 R482-mutants in TM3, 4 N557-mutants in TM5 and 6 H630-mutants in TM6) and examined the effect of the substitutions on cellular drug resistance. PA317 cells transfected with any one of the 7 E446-mutant BCRP cDNAs did not show drug resistance. Cells transfected with any one of the 13 R482X2-BCRP cDNAs (X2 = N, C, M, S, T, V, A, G, E, W, D, Q and H, but not Y and K) showed higher resistance to mitoxantrone and doxorubicin than the wild-type BCRP-transfected cells. Cells transfected with N557D-BCRP cDNA showed similar resistance to mitoxantrone but lower resistance to SN-38 than the wild-type BCRP-transfected cells. Cells transfected with N557E-, H630E- or H630L-BCRP cDNA showed similar degrees of resistance to mitoxantrone and SN-38. Estrone and fumitremorgin C reversed the drug resistance of cells transfected with R482-, N557- or H630-mutant BCRP cDNA. Cells transfected with R482G- or R482S-BCRP cDNA showed less intracellular accumulation of [3H]mitoxantrone than the wild-type BCRP-transfected cells. These results suggest that E446 in TM2, R482 in TM3, N557 in TM5 and H630 in TM6 play important roles in drug recognition of BCRP.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1995

MRP gene overexpression in a human doxorubicin-resistant SCLC cell line: alterations in cellular pharmacokinetics and in pattern of cross-resistance.

The development of non-P-glycoprotein-mediated multi-drug resistance is a frequent event among lung-cancer cell lines. In an attempt to understand the underlying mechanisms of this phenotype, we have selected a multi-drug-resistant subline (POGB/DX) in vitro for doxorubicin resistance. The original cell line (POGB) was established in vitro from a non-treated patient with a small-cell lung cancer. POGB/DX cells were cross-resistant to other drugs, associated with MDR phenotype. In contrast, they were not resistant to taxol, camptothecin or melphalan, but were instead hypersensitive to 5-fluorouracil. Although expression of the mdr-1 gene was not detected in POGB/DX cells, cellular pharmacokinetics showed a reduced drug accumulation and altered intracellular localization in the POGB/DX cell line. This defect in drug accumulation was associated with overexpression and amplification of the MRP gene. Interestingly, verapamil, a known modulator of P-glycoprotein function, was able to reverse drug resistance and to increase drug accumulation. In Northern-blot analysis no differences in expression of topoisomerase I and II (alpha and beta), DNA polymerase beta, or HSP70 and HSP60 genes were observed between POGB and POGB/DX. Coupled to lack of changes in expression of known resistance factors, overexpression of MRP and modulation by verapamil strongly support a role for this gene product in the development of drug resistance in this SCLC cell system. This study provides evidence that (a) altered cellular pharmacokinetics is related to MRP expression; (b) MRP-mediated phenotype is characterized by a specific pattern of cross-resistance, which does not involve taxol; and (c) verapamil may be effective in modulating the function of the MRP gene product.

Carcinoma, Small Cell↗
PubMed1989

An epidermal growth factor-ricin A chain (EGF-RTA)-resistant mutant and an epidermal growth factor-Pseudomonas endotoxin (EGF-PE)-resistant mutant have distinct phenotypes.

H2Oe12 is a mutant HeLa cell line selected for resistance to the toxicity of a chimeric protein conjugate composed of epidermal growth factor (EGF) and the toxic A chain of ricin (RTA). ET-28 is a mutant KB cell line selected for resistance to the toxicity of a chimeric protein conjugate composed of EGF and Pseudomonas exotoxin (PE). In this report we describe the presence or absence, in these mutants, of cross-resistance to the two toxic conjugates and the effects of ammonium chloride, leupeptin, and adenovirus cotreatments on toxin efficacies. ET-28 cells, the EGF-PE-resistant cells, are resistant to both EGF-PE and EGF-RTA. In contrast, H2Oe12 cells, the EGF-RTA-resistant cells, are as sensitive to EGF-PE toxicity as are their parent HeLa cells. Ammonium chloride cotreatment substantially reduces the resistance of H2Oe12 cells to EGF-RTA but has little or no effect on the resistance of ET-28 cells to either EGF-RTA or EGF-PE. Leupeptin has no effect on the toxicity of either chimeric conjugate on any of the four cell lines, effect on the toxicity of either chimeric conjugate on any of the four cell lines, despite its demonstrated ability to inhibit cellular degradation of EGF. In contrast, adenovirus cotreatment enhances the toxicity of EGF-RTA and EGF-PE on all cells tested, and completely nullifies the relative resistance of H2Oe12 and ET-28 cells to these toxic conjugates. H2Oe12 and ET-28 cells appear to be altered in distinct, possibly endosomal, functions.

ADP Ribose Transferases↗
PubMed2005

Correlation of a resistance-associated Rdl mutation in the German cockroach, Blattella germanica (L), with persistent dieldrin resistance in two Danish field populations.

Danish Blattella germanica (L) populations carry the resistance-associated mutation A302S within the Resistance to dieldrin (Rdl) gene. The mutation has remained in field populations long after the discontinuation of dieldrin for cockroach control. The mutation has also persisted in our laboratory strains with high and intermediate frequencies for more than 8 years without selection. The toxicity of dieldrin was tested by topical application to male cockroaches in the susceptible strain DPIL-SUS and two field strains, Zo960302 and Su960304, which were 1270- and 15-fold resistant to dieldrin at LD50. We report the sequencing of exon 7 of the B. germanica Rdl gene and the finding of the putative resistance-associated A302S mutation. We have developed and implemented a PCR-based diagnostic method with the detection of a restriction endonuclease polymorphism, which allows for easy discrimination of susceptible, resistant and heterozygote genotypes. The frequency of the resistance-associate allele A302S was 0.97 and 0.38 in the Zo960302 and Su960304 populations, respectively. The cockroach Rdl A302S allele confers high dieldrin resistance in homozygotes and intermediate resistance in heterozygotes, and its presence is responsible for the persisting dieldrin resistance in Danish populations of B. germanica.

Amino Acid Sequence↗
PubMed2001

Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells.

Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1996

Cross-resistance, cisplatin accumulation, and platinum-DNA adduct formation and removal in cisplatin-sensitive and -resistant human hepatoma cell lines.

The BEL7404 human hepatoma cell line was selected in vitro for primary cisplatin resistance. A panel of four cisplatin-resistant sublines were generated which exhibited resistance to cisplatin (up to 34-fold) but were not cross-resistant to adriamycin, taxol, etoposide, or mitomycin C. Further characterization of this panel of cell lines revealed that increased cisplatin resistance was associated with decreased cisplatin accumulation in the selected sublines (up to 14-fold) relative to the parental BEL7404 cell line. A significant reduction in platinum-DNA adduct formation (9-fold) and ribosomal RNA gene-specific interstrand crosslink formation (12-fold) were also observed in the 7404-CP20 cell line. No differences in the rate of platinum efflux from the BEL7404 and 7404-CP20 cell lines were detected following a 4-h loading period, and total platinum-DNA adduct and gene-specific interstrand crosslink removal rates were similar in both cell lines. There were approximately 3-fold more total platinum-DNA adducts present in the BEL7404 cells relative to the 7404-CP20 cells at equitoxic concentrations of cisplatin, suggesting that DNA damage tolerance also contributes to the cisplatin resistance phenotype. Overall, these results indicate that decreased cisplatin accumulation is the major cisplatin resistance mechanism present in the in vitro-selected cell lines. This model system of acquired cisplatin resistance may be valuable in determining the molecular basis for decreased cisplatin uptake and be useful for the study of potential resistance modulators.

Carcinoma, Hepatocellular↗
PubMed1992

Diversity of resistance phenotypes and plasmid analysis in multi-resistant 0:12 Pseudomonas aeruginosa.

Antibiotic resistance phenotypes, plasmid content and ability of conjugal transfer of antibiotic resistance genes of 35 multi-resistant Pseudomonas aeruginosa strains were examined. The strains were isolated in 12 Greek hospitals and the majority of them (80%) belonged to serotype 0:12. The isolates were distributed to a variety of different antibiotic resistance phenotypes. Plasmid analysis showed that 10 isolates harboured plasmids ranging in size from 20 to 100 Mda. Among these strains, four carried plasmids of 100 Mda, two strains had 60 Mda plasmid each while in three strains the plasmids detected were 65, 25 and 20 Mda, respectively. One strain harboured two plasmids of 100 and 60 Mda. All strains containing plasmids belonged to 0:12 serotype, except the one harbouring the 25 Mda plasmid, which belonged to serotype 0:6. Using a P. aeruginosa recipient resistant to rifampicin and ciprofloxacin, conjugal transfer was achieved in two occasions. These plasmids, 100 Mda in size, encoded high-level resistance to both gentamicin and tobramycin whereas resistance to other drugs was not transferable. Interestingly, all 100 Mda plasmids, including the self-transferable ones, were found to share a certain degree of homology as judged by restriction analysis. It is suggested that both resistance phenotypes and analysis of plasmid content might be useful in subdividing 0:12 multi-resistant P. aeruginosa.

Drug Resistance, Microbial↗
PubMed1987

The mechanism and overcoming of resistance in ACNU-resistant sublines of C6 and 9L rat glioma.

In order to study the mechanism of the resistance to chemotherapeutic agents, especially ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU were selected in vivo from rat C6 and 9L glioma, respectively. Uptake and efflux of ACNU in these resistant cells were studied with Ethylene[14C]ACNU. The result indicated that the resistance exhibited by both sublines were due to both the reduced uptake of the drug and the increased efflux. The study of the effects of oxidative phosphorylation inhibitor, DNP (2,4-dinitrophenol), on the uptake and retention of ACNU suggested that there is an active outward transport mechanism for ACNU in both glioma sublines and that enhanced activity of this efflux mechanism renders cells highly resistant to the cytotoxic action of ACNU. In an attempt to clarify the more detailed biochemical mechanisms of this active efflux system, we surveyed various membrane-modifying agents which potentiate the sensitivity of these resistant cells to ACNU. Among a number of membrane-modifying agents, reserpine was found to retain ACNU in the resistant cells and to enhance the action of ACNU on these resistant cell lines. It may be concluded that drugs such as reserpine may overcome a mechanism of ACNU resistance.

Animals↗
PubMed1995

The nickel resistance determinant cloned from the enterobacterium Klebsiella oxytoca: conjugational transfer, expression, regulation and DNA homologies to various nickel-resistant bacteria.

Klebsiella oxytoca strain CCUG 15788, isolated from a mineral oil emulsion tank in Göteborg, Sweden, was found to be nickel-resistant (tolerating 10 mM NiCl2 in non-complexing mineral-gluconate media; inducible resistance). The nickel resistance determinants were transferred by helper-assisted conjugation to various strains of Escherichia coli and Citrobacter freundii and expressed to between 5 and 10 mM NiCl2. A 4.3 kb HindIII fragment was cloned from the genomic DNA of K. oxytoca. Ligated into the vector pSUP202, the fragment caused constitutive nickel resistance (of up to 3 or 10 mM Ni2+) in various E. coli strains. After cloning into the broad host range vector pVDZ'2 the fragment even expressed low nickel resistance in the transconjugant of Alcaligenes eutrophus AE104. With the 4.3 kb HindIII fragment as a biotinylated DNA probe it was shown by DNA-DNA hybridization that the nickel resistance determinant resides on the chromosome of K. oxytoca and not on its circular plasmid pKO1 (160 kb) or linear plasmid pKO2 (50 kb). Nickel resistance strongly correlated with the presence of the 4.3 kb HindIII fragment in the transconjugants. No homologies were detected when the nickel resistance determinants of other well-known nickel-resistant bacteria, such as A. eutrophus CH34 or A. denitrificans 4a-2, were used as target DNA. Among the 60 strains examined, positive signals only appeared with the 3.1 kb DNA fragment from A. xylosoxydans 31A and the genomic DNA of two enterobacterial strains (5-1 and 5-5) isolated from nickel-rich soil in New Caledonia.

Cloning, Molecular↗