scholarly journals Trimethoprim-resistant mutants ofE. coliK12: preliminary genetic mapping

1975 ◽  
Vol 25 (3) ◽  
pp. 207-214 ◽  
Author(s):  
A. S. Breeze ◽  
P. Sims ◽  
K. A. Stacey
Keyword(s):  
Genetic Mapping ◽  
Structural Gene ◽  
Dihydrofolate Reductase ◽  
Bacteriophage P1 ◽  
E Coli ◽  
Resistant Mutants ◽  
High Level ◽  
Increased Activity ◽  
Level Resistance ◽  
Target Enzyme

SUMMARYTrimethoprim-resistant mutants ofE. coliK12 have been isolated by-serial subculture in progressively higher concentrations of trimethoprim. High-level resistance depends on the accumulation of several mutational changes. Transduction with bacteriophage P1 has shown that all the mutations involved in resistance are associated with a locus, to be calledtmr, betweenpyr AandpdxAand closely linked topdxA. Resistance is accompanied by, and presumably due to, an increased activity of the target enzyme, dihydrofolate reductase. Thetmrlocus may include the structural gene for dihydrofolate reductase but the only mutations that have so far been observed are concerned with regulation.

scholarly journals Antimicrobial Resistance of DiarrheagenicEscherichia coli Isolated from Children under the Age of 5 Years from Ifakara, Tanzania

1999 ◽  
Vol 43 (12) ◽  
pp. 3022-3024 ◽  
Author(s):  
Jordi Vila ◽  
Martha Vargas ◽  
Climent Casals ◽  
Honorato Urassa ◽  
Hassan Mshinda ◽  
...  
Keyword(s):  
Developing Countries ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Important Public Health Problem ◽  
Important Public Health ◽  
E Coli ◽  
High Level ◽  
Level Resistance ◽  
Children Under 5

ABSTRACT Diarrhea caused by multidrug-resistant bacteria is an important public health problem among children in developing countries. The prevalence and antimicrobial susceptibility of diarrheagenicEscherichia coli in 346 children under 5 years of age in Ifakara, Tanzania, were studied. Thirty-eight percent of the cases of diarrhea were due to multiresistant enterotoxigenic E. coli, enteroaggregative E. coli, or enteropathogenicE. coli. Strains of all three E. colicategories showed high-level resistance to ampicillin, tetracycline, co-trimoxazole, and chloramphenicol but were highly susceptible to quinolones. Guidelines for appropriate use of antibiotics in developing countries need updating.

scholarly journals Outbreak Caused by NDM-1- and RmtB-Producing Escherichia coli in Bulgaria

2014 ◽  
Vol 58 (4) ◽  
pp. 2472-2474 ◽  
Author(s):  
Laurent Poirel ◽  
Encho Savov ◽  
Arzu Nazli ◽  
Angelina Trifonova ◽  
Iva Todorova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
16S Rrna ◽  
Sequence Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
The World ◽  
High Level ◽  
16S Rrna Methylase ◽  
Level Resistance

ABSTRACTTwelve consecutive carbapenem-resistantEscherichia coliisolates were recovered from patients (infection or colonization) hospitalized between March and September 2012 in different units at a hospital in Bulgaria. They all produced the carbapenemase NDM-1 and the extended-spectrum-β-lactamase CTX-M-15, together with the 16S rRNA methylase RmtB, conferring high-level resistance to all aminoglycosides. All those isolates were clonally related and belonged to the same sequence type, ST101. In addition to being the first to identify NDM-producing isolates in Bulgaria, this is the very first study reporting an outbreak of NDM-1-producingE. coliin the world.

scholarly journals Genetic Characterization of Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis

2003 ◽  
Vol 47 (4) ◽  
pp. 1419-1422 ◽  
Author(s):  
Adela G. de la Campa ◽  
María-José Ferrandiz ◽  
Fe Tubau ◽  
Román Pallarés ◽  
Federico Manresa ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Genetic Characterization ◽  
Susceptible Strain ◽  
Low Level ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
High Level ◽  
Level Resistance

ABSTRACT Five Spain9V-3 Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible S. pneumoniae may select fluoroquinolone-resistant mutants.

scholarly journals Role of β-Lactamases and Porins in Resistance to Ertapenem and Other β-Lactams in Klebsiella pneumoniae

2004 ◽  
Vol 48 (8) ◽  
pp. 3203-3206 ◽  
Author(s):  
George A. Jacoby ◽  
Debra M. Mills ◽  
Nancy Chow
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Type Strain ◽  
Wild Type Strain ◽  
Outer Membrane Proteins ◽  
Wild Type ◽  
Resistant Mutants ◽  
High Level ◽  
Level Resistance

ABSTRACT High-level resistance to ertapenem was produced by β-lactamases of groups 1, 2f, and 3 in a strain of Klebsiella pneumoniae deficient in Omp35 and Omp36. From a wild-type strain producing ACT-1 β-lactamase, ertapenem-resistant mutants for which the ertapenem MICs were up to 128 μg/ml and expression of outer membrane proteins was diminished could be selected.

Identification of a novel plasmid-encoded dihydrofolate reductase mediating high-level resistance to trimethoprim

1988 ◽  
Vol 22 (4) ◽  
pp. 429-435 ◽  
Author(s):  
B. A. Wylie ◽  
S. G. B. Amyes ◽  
H.-K. Young ◽  
H. J. Koornhof
Keyword(s):  
Dihydrofolate Reductase ◽  
High Level ◽  
Level Resistance

scholarly journals High-Level Pacidamycin Resistance in Pseudomonas aeruginosa Is Mediated by an Opp Oligopeptide Permease Encoded by theopp-fabIOperon

2013 ◽  
Vol 57 (11) ◽  
pp. 5565-5571 ◽  
Author(s):  
Anita Mistry ◽  
Mark S. Warren ◽  
John K. Cusick ◽  
RoxAnn R. Karkhoff-Schweizer ◽  
Olga Lomovskaya ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Frequency ◽  
Cross Resistance ◽  
Peptide Antibiotics ◽  
Content Type ◽  
Resistant Mutants ◽  
High Level ◽  
Level Resistance ◽  
Resistance Mutants

ABSTRACTPacidamycins (or uridyl peptide antibiotics) possess selectivein vivoactivity againstPseudomonas aeruginosa. An important limitation for the therapeutic use of pacidamycins withP. aeruginosais the high frequency (10−6to 10−7) at which resistant mutants emerge. To elucidate the mechanism(s) of this resistance, pacidamycin-resistantP. aeruginosamutants were isolated. Two types of mutants were obtained. Type 1, or high-level resistance mutants with a pacidamycin MIC of 512 μg/ml, were more abundant, with a frequency of ∼2 × 10−6, and did not show cross-resistance with other antibiotics. Type 2, low-level resistance mutants, were isolated with a frequency of ∼10−8and had a pacidamycin MIC of 64 μg/ml (the MIC for the wild-type strain was 4 to 16 μg/ml). These mutants were cross-resistant to levofloxacin, tetracycline, and erythromycin and were shown to overexpress either the MexAB-OprM or MexCD-OprJ multidrug resistance efflux pumps. High-level resistant mutants were isolated by transposon mutagenesis and one insertion was localized tooppB, one of two periplasmic binding protein components of an oligopeptide transport system which is encoded by theopp-fabIoperon. The Opp system is required for uptake of pacidamycin across the inner membrane, since variousopp, but notfabI, mutants were resistant to high levels of pacidamycin. Both of the two putative Opp periplasmic binding proteins, OppA and OppB, were required for pacidamycin uptake. Although both impaired uptake into and efflux from the cell can cause pacidamycin resistance inP. aeruginosa, our data suggest that impaired uptake is the primary reason for the high-frequency and high-level pacidamycin resistance.

scholarly journals Plasmid-Mediated Resistance to Extended-Spectrum Cephalosporins and Resistance to Fluoroquinolones in Escherichia Coli Isolates from Black-headed Gulls (Larus Ridibundus)

2021 ◽  
Author(s):  
Maja Velhner ◽  
Dalibor Todorović ◽  
Katarina Novović ◽  
Branko Jovčić ◽  
Gospava Lazić ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
E Coli ◽  
Extended Spectrum ◽  
Cephalosporin Antibiotics ◽  
High Level ◽  
Group D ◽  
Sequence Types ◽  
Replicon Type ◽  
Level Resistance ◽  
Game Animals

Abstract Although resistance to fluoroquinolones is common in E. coli isolates from farm and game animals in Serbia, currently no data are accessible on the occurrence of antibacterial resistances in E. coli isolates from gulls. Therefore, 45 cloacal swabs and 50 fecal samples from black-headed gulls were investigated for the presence of Escherichia coli isolates resistant to antibiotics. Multidrug resistance was detected in 22 E. coli isolates. High level resistance to fluoroquinolones was found in ten isolates with MIC values of ciprofloxacin ranging from 4 to 32 mg/L. Genotyping revealed single or double mutations in the quinolone resistance determining region (QRDR) of the gyrA or gyrA, parC and parE genes, respectively. Ten isolates showed resistance to extended-spectrum cephalosporin antibiotics. These ten isolates belonged to phylogenetic group B2 (five isolates), group D (four isolates) and group B1 (one isolate). An extended-spectrum β-lactamase resistance phenotype was detected in one isolate which carried the blaCTX-M-1 gene on a plasmid of the I2/FIB replicon type. Nine isolates carried blaCMY-2 genes, which were detected on conjugative plasmids in seven isolates. One transconjugant also carried hly, iroN, iss, ompT and cvaC virulence genes on the plasmid. Five different sequence types (ST38, ST2307, ST224, ST162 and ST34) were detected in E. coli isolates with ESBL or AmpC phenotype and genotype.

scholarly journals Development of antibacterial compounds that constrain evolutionary pathways to resistance

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yanmin Zhang ◽  
Sourav Chowdhury ◽  
João V Rodrigues ◽  
Eugene I Shakhnovich
Keyword(s):  
Dihydrofolate Reductase ◽  
Experimental Approach ◽  
Whole Genome ◽  
Bacterial Protein ◽  
Antibacterial Compounds ◽  
E Coli ◽  
Resistant Strains ◽  
Evolutionary Pathways ◽  
Resistant Mutants

Antibiotic resistance is a worldwide challenge. A potential approach to block resistance is to simultaneously inhibit WT and known escape variants of the target bacterial protein. Here we applied an integrated computational and experimental approach to discover compounds that inhibit both WT and trimethoprim (TMP) resistant mutants of E. coli dihydrofolate reductase (DHFR). We identified a novel compound (CD15-3) that inhibits WT DHFR and its TMP resistant variants L28R, P21L and A26T with IC50 50-75 µM against WT and TMP-resistant strains. Resistance to CD15-3 was dramatically delayed compared to TMP in in vitro evolution. Whole genome sequencing of CD15-3 resistant strains showed no mutations in the target folA locus. Rather, gene duplication of several efflux pumps gave rise to weak (about twofold increase in IC50) resistance against CD15-3. Altogether, our results demonstrate the promise of strategy to develop evolution drugs - compounds which constrain evolutionary escape routes in pathogens.

scholarly journals Sequence Analysis of the gyrA andparC Homologues of a Wild-Type Strain of Vibrio parahaemolyticus and Its Fluoroquinolone-Resistant Mutants

1999 ◽  
Vol 43 (5) ◽  
pp. 1156-1162 ◽  
Author(s):  
Jun Okuda ◽  
Eriko Hayakawa ◽  
Mitsuaki Nishibuchi ◽  
Takeshi Nishino
Keyword(s):  
Vibrio Parahaemolyticus ◽  
Resistance Mechanism ◽  
Point Mutations ◽  
Erwinia Carotovora ◽  
Open Reading Frames ◽  
Fluoroquinolone Resistance ◽  
Degenerate Primers ◽  
Resistant Mutants ◽  
High Level ◽  
Level Resistance

ABSTRACT Vibrio parahaemolyticus causes seafood-borne gastroenteritis in humans. It is particularly important in Japan, where raw seafood is frequently consumed. Fluoroquinolone is one of the current drugs of choice for treating patients infected by V. parahaemolyticus because resistant strains are rarely found. To study a possible fluoroquinolone resistance mechanism in this organism, nucleotide sequences that are homologous to known gyrA andparC genes have been cloned from V. parahaemolyticus AQ3815 and sequenced by amplification with degenerate primers of the quinolone resistance-determining region (QRDR), followed by cassette ligation-mediated PCR. Open reading frames encoding polypeptides of 878 and 761 amino acid residues were detected in the gyrA and parC homologues, respectively. The V. parahaemolyticus GyrA and ParC sequences were most closely related to Erwinia carotovora GyrA (76% identity) and Escherichia coli ParC (69% identity) sequences, respectively. Ciprofloxacin-resistant mutants of AQ3815 were obtained on an agar medium by multistep selection with increasing levels of the quinolone. One point mutation only in the gyrA QRDR was detected among mutants with low- to intermediate-level resistance, while point mutations in both the gyrA and parCQRDRs were detected only in strains with high-level resistance. These results strongly suggest that, as in other gram-negative bacteria, GyrA and ParC are the primary and secondary targets, respectively, of ciprofloxacin in V. parahaemolyticus.

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