Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study determined the prevalence of antimicrobial resistance by Neisseria gonorrhoeae, including penicillinase-producing gonorrhea (PPNG) strains, and monitored the trends. It further compared the results of antimicrobial sensitivity by disc diffusion and minimum inhibitory concentration (MIC). A total of 211 confirmed gonorrhea strains were subjected to antimicrobial sensitivity testing by disc diffusion using penicillin, tetracycline, ciprofloxacin, and ceftriaxone from 1995 to June 1999. PPNG strains were detected by lodometric method, and an E test method of 55 strains isolated in 1997-98 determined MIC. Statistical analysis of the results indicates that a low level of penicillin resistance and PPNG detected in 1996 was maintained over the years. In addition, a significant increasing trend of tetracycline and ciprofloxacin resistance with high MIC was found. Ceftriaxone, being 100% sensitive, was found to be the drug of choice. Moreover, comparison of resistance pattern by the two tests showed satisfactory agreement. Findings indicate the need for increased awareness, prudent use of antimicrobials, and evaluation of new antimicrobials for the treatment of gonorrhea.
Int J STD AIDS 2000 Feb
PMID:Trend of antimicrobial resistance in Neisseria gonorrhoeae at New Delhi, India. 1067 80

PSE-4 is a class A beta-lactamase produced by strains of Pseudomonas aeruginosa and is highly active for the penicillin derivative carbenicillin. The crystal structure of the wild-type PSE-4 carbenicillinase has been determined to 1.95 A resolution by molecular replacement and represents the first structure of a carbenicillinase published to date. A superposition of the PSE-4 structure with that of TEM-1 shows a rms deviation of 1.3 A for 263 Calpha atoms. Most carbenicillinases are unique among class A beta-lactamases in that residue 234 is an arginine (ABL standard numbering scheme), while in all other class A enzymes this residue is a lysine. Kinetic characterization of a R234K PSE-4 mutant reveals a 50-fold reduction in k(cat)/K(m) and confirms the importance of Arg 234 for carbenicillinase activity. A comparison of the structure of the R234K mutant refined to 1.75 A resolution with the wild-type structure shows that Arg 234 stabilizes an alternate conformation of the Ser 130 side chain, not seen in other class A beta-lactamase structures. Our molecular modeling studies suggest that the position of a bound carbenicillin would be shifted relative to that of a bound benzylpenicillin in order to avoid a steric clash between the carbenicillin alpha-carboxylate group and the conserved side chain of Asn 170. The alternate conformation of the catalytic Ser 130 in wild-type PSE-4 may be involved in accommodating this shift in the bound substrate position.
...
PMID:Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies. 1114 33

A pCb plasmid encoding a beta-lactamase from Haemophilus ducreyi was transferred to Escherichia coli, purified, and characterized. The beta-lactamase could be isolated from a culture filtrate and further purified by ammonium sulfate and chelating Sepharose fast flow loaded with Zn(2+). The purified enzyme resulted in a major band at approximately 30-kDa on SDS-PAGE and its pI was determined to be 5.4. The beta-lactamase could hydrolyze both penicillin antibiotics including ampicillin, benzylpenicillin, and carbenicillin as well as cephalosporin antibiotics including nitrocefin, cephalothin, cephaloridine, and cefoperazone. However, benzylpenicillin was the best substrate. The enzyme activity was inhibited by clavulanic acid but not by boric acid, cefotaxime, ethylenediaminetetraacetic acid, or phenylmethylsulfonyl fluoride. The sequence of the beta-lactamase gene was also determined. It confirmed that the enzyme belonged to a class A beta-lactamase which had 99% identity to the ampicillin resistance transposon Tn3 of pBR322. Two nucleotides were different between the E. coli (Tn3) and H. ducreyi (pCb) genes that affected the amino-acid sequence. The valine at position 82 (ABL 84) was changed to isoleucine and the alanine at position 182 (ABL 184) was changed to valine. Genetic homogeneity among beta-lactamases is remarkable. Amino acid sequencing of some beta-lactamases has shown that substitution of only a few amino acids in the bla gene leads to high-level resistance against specific cephalosporins.
...
PMID:Purification and characterization of a beta-lactamase from Haemophilus ducreyi in Escherichia coli. 1157 Aug 57

Antimicrobial susceptibility testing was performed on isolates of Neisseria gonorrhoeae obtained from patients attending the City Health STD clinic in Durban, KwaZuluNatal, using the following drugs: penicillin, tetracycline, ciprofloxacin, ofloxacin, ceftriaxone, spectinomycin, erythromycin and azithromycin. These isolates were collected over a 6 year period from 1995 to 2000. Four hundred and fifteen strains were tested: 61 in 1995, 198 in 1997, 98 in 1998/99 and 58 in 1999/2000. A shift to the right is observed in the susceptibilities of N. gonorrhoeae to the currently recommended drugs in the syndromic management guidelines viz. penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin and erythromycin. The prevalence of penicillinase-producing N. gonorrhoeae is currently c. 30%, whereas that of plasmid-mediated tetracycline-resistant N. gonorrhoeae is c. 50%. There is a definite association between the MICs of strains falling within the penicillin and tetracycline chromosomally resistant group, and strains exhibiting a decreased susceptibility to ciprofloxacin and ceftriaxone. The MICs of azithromycin showed a similar distribution when compared with erythromycin for 1999/2000 isolates. We postulate that the presence of efflux pumps might play a role in the increasing MICs that we observe among structurally unrelated groups of drugs. Furthermore, widespread use of these antimicrobials in the community may offer a selective advantage to the development of resistance. The implications of this are far reaching and the local susceptibility trends of N. gonorrhoeae need to be monitored constantly to direct therapy.
...
PMID:Evolution in the trends of antimicrobial resistance in Neisseria gonorrhoeae isolated in Durban over a 5 year period: impact of the introduction of syndromic management. 1173 69

The aim of this study was to compare epidemiological data with antibiotic susceptibility patterns, so as to characterize the risk of infection with a highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in Sweden from February 1998 through January 1999 were tested for antibiotic susceptibility. Epidemiological data were received from each clinician reporting a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases diagnosed during the 12-month period, were tested for antibiotic susceptibility. Of all isolates, 24% were beta-lactamase-producing, and 18% had decreased susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were fully susceptible to azithromycin. The antibiotic susceptibility varied with the places where patients were exposed to infection. When exposed in Asia, 63% of the isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of the isolates from patients exposed in other places (RR=8.5, P<0.001). Ciprofloxacin cannot be recommended as the first choice of treatment if the place of exposure was in Asia.
Int J STD AIDS 2002 Feb
PMID:One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure. 1183 65

Strains of Neisseria gonorrhoeae are generally characterized by auxotyping, serotyping, plasmid profile, antibiotic sensitivity and deoxyribonucleic acid (DNA) amplification fingerprinting. The aim of this study was to analyse the generation of restriction fragment length polymorphism (RFLP) patterns by BgIII digestion of total genomic DNA of N. gonorrhoeae isolated from the community (n =30) and the hospital (n =15) and to establish an association with serogrouping and antibiogram. The RFLP patterns produced by BgIII restriction digestion showed 7 different patterns among 30 community isolates and 9 different patterns among 15 hospital isolates. 66.7% of isolates belonged to serogroup WI. Penicillin resistance was observed in 46.7% of community isolates and 66.7% hospital isolates. However, penicillinase producing N. gonorrhoeae (PPNG) were lower in the community (6.6%) than in the hospital isolates (53.3%). PPNG strains were more often seen in serogroup WI. This is the first Indian report on RFLP genotype pattern in N. gonorrhoeae. We noted differences in RFLP genotypes of the community (RFLP types 1, 2, 3, 4, 5 and 7) and hospital strains (RFLP types 6 and 8), while no differences in the serogroup were observed. Ciprofloxacin resistance was 20.0% and 26.6% in the community and hospital isolates, respectively. Ceftriaxone emerges as the current drug of choice for an effective policy of antibiotic treatment of gonorrhoea through syndromic management in developing countries.
Int J STD AIDS 2002 Feb
PMID:Molecular typing of Neisseria gonorrhoeae from hospital and community isolates by restriction fragment length polymorphism. 1183 68

We have previously described a strategy for detecting protein protein interactions based on protein interaction assisted folding of rationally designed fragments of enzymes. We call this strategy the protein fragment complementation assay (PCA). Here we describe PCAs based on the enzyme TEM-1 beta-lactamase (EC: 3.5.2.6), which include simple colorimetric in vitro assays using the cephalosporin nitrocefin and assays in intact cells using the fluorescent substrate CCF2/AM (ref. 6). Constitutive protein protein interactions of the GCN4 leucine zippers and of apoptotic proteins Bcl2 and Bad, and the homodimerization of Smad3, were tested in an in vitro assay using cell lysates. With the same in vitro assay, we also demonstrate interactions of protein kinase PKB with substrate Bad. The in vitro assay is facile and amenable to high-throughput modes of screening with signal-to-background ratios in the range of 10:1 to 250:1, which is superior to other PCAs developed to date. Furthermore, we show that the in vitro assay can be used for quantitative analysis of a small molecule induced protein interaction, the rapamycin-induced interaction of FKBP and yeast FRB (the FKBP-rapamycin binding domain of TOR (target of rapamycin)). The assay reproduces the known dissociation constant and number of sites for this interaction. The combination of in vitro colorimetric and in vivo fluorescence assays of beta-lactamase in mammalian cells suggests a wide variety of sensitive and high-throughput large-scale applications, including in vitro protein array analysis of protein protein or enzyme protein interactions and in vivo applications such as clonal selection for cells expressing interacting protein partners.
...
PMID:Beta-lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein protein interactions. 1204 68

Four known and nine new ceftazidime-resistance beta-lactamases were generated by a novel, contaminating codon-based mutagenesis approach. In this method, wild-type codons are spiked with a set of mutant codons during oligonucleotide synthesis, generating random combinatorial libraries of primers that contain few codon replacements per variant. Mutant codons are assembled by tandem addition of a diluted mixture of five Fmoc-dimer amidites to the growing oligo and a mixture of four DMTr-monomer amidites to generate 20 trinucleotides that encode a set of 18 amino acids. Wild-type codons are assembled with conventional chemistry and the whole process takes place in only one synthesis column, making its automation feasible. The random and binomial behavior of this approach was tested in the polylinker region of plasmid pUC19 by the synthesis of three oligonucleotide libraries mutagenized at different rates and cloned as mutagenic cassettes. Additionally, the method was biologically assessed by mutating six contiguous codons that encode amino acids 237-243 (ABL numbering) of the TEM(pUC19) beta-lactamase, which is functionally equivalent to the clinically important TEM-1 beta-lactamase. The best ceftazidime-recognizing variant was a triple mutant, R164H:E240K: R241A, displaying a 333-fold higher resistance than the wild-type enzyme.
...
PMID:Novel ceftazidime-resistance beta-lactamases generated by a codon-based mutagenesis method and selection. 1217 12

In 1986-1987, health workers at the Banaras Hindu University Hospital in Varanasi, India took gonococcal smears from both men and women so laboratory personnel could test for detection of penicillinase-producing Neisseria gonorrhoea (PPNG). None of the cultures tested positive for PPNG. They were detected in 3 cases in Varanasi in 1983, however. Nevertheless PPNG strains remained rare in Varanasi. The 1st reported case of PPNG occurred in Madras in 1981. In 1989, only 52 cases of PPNG had been reported nationwide. The researchers suggested that such a low yield of PPNG isolates may be due to underreporting of STDs in general and inadequate laboratories and equipment to culture gonococci at most centers. Furthermore, many health practitioners treat urethritis patients without laboratory confirmation and switch antibiotics at the 1st possible sign of treatment failure. The researchers proposed educating practitioners about wise use of recommended effective STD therapies to not deplete the antimicrobial reserve. In addition, researchers should conduct studies to determine the exact prevalence of PPNG strains in an area. They should also conduct studies on treatment failure rates with the 1st line drug of choice to monitor drug efficacy. For example, cure rates 90% should be unacceptable for gonorrhea. They concluded by advocating the provision of a test for penicillinase production at all centers in India.
...
PMID:Penicillinase-producing Neisseria gonorrhoeae infection in India. 1228 32

Neisseria gonorrhoeae isolates that were resistant to ciprofloxacin and/or penicillin were analysed to investigate the escalating problem of antibiotic-resistant gonorrhoea in the north east of England. Opa-typing (outer membrane opacity protein) was carried out on isolates resistant to ciprofloxacin and of nutrient nonrequiring (NR) auxotype. In the year 2000 there were 265 cases of gonorrhoea, of which 44 (16.6%) were resistant to penicillin and 12 (4.5%) were resistant or had reduced sensitivity to ciprofloxacin (with only four of these acquired outside the UK). Three (7.5%) of the non-beta-lactamase penicillin-resistant isolates were imported from abroad. By Opa-typing of ciprofloxacin-resistant strains, one pair of the isolates was similar, two were unique and one was similar to the Oldham/Rochdale outbreak strain described early in 2000. This marked increase in the prevalence of indigenous ciprofloxacin resistance requires continued surveillance and may soon necessitate an alteration in our first line treatment.
Int J STD AIDS 2002 Dec
PMID:What is new with antibiotic-resistant gonorrhoea in Newcastle, England? 1253 30


<< Previous 1 2 3 4 5 6 Next >>

---