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

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

Between 1986 and 1992, 15% of all cases of penicillinase-producing Neisseria gonorrhoeae (PPNG) notified in the UK were seen at our central London clinic. During this time the geographical provenance of PPNG has changed. Africa and SE Asia have been supplanted by the Caribbean as the predominant source, with 21.4% of all cases being directly imported from there in 1992. If all gonococcal infections acquired outside the UK had been assumed to be PPNG, together with those occurring in patients with family origins in Africa or SE Asia, some 60% of cases of PPNG could have been predicted before laboratory confirmation of resistance. There is little evidence that PPNG has become endemic in the United Kingdom.
Int J STD AIDS
PMID:PPNG at St Thomas' Hospital--a changing provenance. 830 73

In three randomised, multicentre studies, azithromycin treatment (1g) as a single dose was administered to patients with uncomplicated gonococcal and non-gonococcal urethritis attending STD Research Laboratories in Lagos, Jos and Ibadan; between January 1989 and December, 1990. One hundred and eighty three patients, comprising 106 males and 77 females who had infections were evaluable at the end of the treatment. Of these 71% of the N. gonorrhoeae isolates were penicillinase producers (PPNG), while 39% were non-PPNG. One hundred and fourteen (95%) of 120 patients with gonococcal urethritis including 104 cases due to penicillinase producing Neiserria gonorrhoeae (PPNG) were clinically and bacteriologically cured with a single 1g dose of azithromycin. Fifty-four (90%) out of 60 patients with non-gonococcal urethritis were cured whilst administered the same dose of azithromycin. The side effects reported for azithromycin were mainly mild and moderate gastro-intestinal complaints and there were no major abnormalities in laboratory parameters. It is concluded that azithromycin was efficacious and safe for the treatment of uncomplicated gonococcal and non-gonococcal infections and may improve patient compliance.
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PMID:Single oral dose of azithromycin for therapy of susceptible sexually transmitted diseases: a multicenter open evaluation. 831 8

During May 1988-October 1990 in Zaire, Neisseria gonorrhoeae isolates were obtained from 650 initially HIV-negative prostitutes in Kinshasa who were followed monthly for 30 months. After conservation of the gonococci, the N. gonorrhoeae isolates were then transported to the Institute of Tropical Medicine in Antwerp, Belgium, to test for antimicrobial resistance, especially tetracycline resistant isolates of N. gonorrhoeae. Among the 1085 isolates, 67% were resistant to penicillin (i.e., penicillinase producing N. gonorrhoeae [PPNG]). 30% exhibited plasmid-mediated resistance to tetracycline (TRNG). 37% were resistant to thiamphenicol. Thiamphenicol resistance was more common in non-TRNG isolates than TRNG isolates (49% vs. 8%; p 0.0001). The frequency of TRNG among PPNG isolates was higher than it was among non-PPNG isolates (37% vs. 16%; p 0.001). PPNG prevalence ranged from 60% to 73%. TRNG prevalence increased steadily from 11% to 45% during the 30-month period. Both TRNG and PPNG isolates were significantly associated with the auxotype/serovar class Pro-/IA-6 (p 0.0001 and p = 0.0002, respectively). They were also associated with growth inhibition by 0.25 mM phenylalanine (p 0.0001 and p = 0.001, respectively). The number of different TRNG auxotype/serovar classes ranged from 6 to 13. It has been suggested that tetracycline use to control gonorrhea in the US and in the Netherlands increased the frequency and spread of TRNG. Only spectinomycin and ciprofloxacin were used to treat gonorrhea in this study. Yet, tetracycline was prescribed for genital Chlamydia trachomatis infection, which many of the prostitutes had. Also, males self-medicate for urethritis with tetracycline. Populations with a high incidence of gonococcal infections may experience an epidemic spread of TRNG.
Int J STD AIDS
PMID:Epidemic spread of plasmid-mediated tetracycline resistant Neisseria gonorrhoeae in Zaire. 854 15

Recently, natural variants of TEM-1 beta-lactamase with amino acid substitutions at residues 237-240 have been identified that have increased hydrolytic activity for extended-spectrum antibiotics such as ceftazidime. To identify the sequence requirements in this region for a given antibiotic, a random library was constructed that contained all possible amino acid combinations for the 3-residue region 237-240 (ABL numbering system) of TEM-1 beta-lactamase. An antibiotic disc diffusion method was used to select mutants with wild-type level activity or greater for the extended-spectrum cephalosporin ceftazidime and the monobactam aztreonam. Mutants that were selected for optimal ceftazidime hydrolysis contained a conserved Ala at position 237, a Ser for Gly substitution at position 238, and a Lys for Glu at position 240. Mutants selected for aztreonam hydrolysis exhibited a Gly for Ala substitution at position 237, a Ser for Gly substitution at position 238, and a Lys/Arg for Glu at position 240. The role of the A237G substitution in differentiating between ceftazidime and aztreonam was further investigated by kinetic analysis of the A237G, E240K, G238S:E240K, and A237G:G238S:E240K enzymes. The A237G single mutant and the G238S:E240K double mutant exhibited increases in catalytic efficiency for both ceftazidime and aztreonam. However, the triple mutant A237G:G238S:E240K, displayed a 12-fold decrease in catalytic efficiency for ceftazidime but a 3-fold increase for aztreonam relative to the G238S:E240K double mutant. Thus, the A237G substitution increases ceftazidime hydrolysis when present alone but antagonizes ceftazidime hydrolysis when it is combined with the G238S:E240K substitutions. In contrast, the A237G substitution acts additively with the G238S:E240K substitutions to increase aztreonam hydrolysis.
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PMID:Selection and characterization of amino acid substitutions at residues 237-240 of TEM-1 beta-lactamase with altered substrate specificity for aztreonam and ceftazidime. 879 21

A new beta-lactamase inhibitor, SYN-1012, with a penem skeleton was synthesized and its biological activity compared with clavulanic acid, sulbactam, tazobactam and BRL-42715. The beta-lactamase inhibitory activity of SYN-1012 was comparable to BRL-42715. Clavulanate and penam sulphones (sulbactam and tazobactam) were more active against TEM-1 and OXA-1, but were less active against TEM-3 and cephalosporinase (Case) than SYN-1012. In combination with piperacillin, SYN-1012 exhibited comparable or slightly lower synergistic effects than BRL-42715 against all the Gram-positive and Gram-negative isolates tested with only exception of Pseudomonas aeruginosa. The separate combinations of SYN-1012 and BRL-42715 with ceftazidime and cefotaxime provided comparable results against Gram-negatives, but not against Gram-positive isolates. Tazobactam was inferior to SYN-1012 in all cases. In comparison to tazobactam, SYN-1012 and BRL-42715 were relatively unstable in human and mouse plasma, and in mouse liver and kidney homogenates. Serum level of SYN-1012 and BRL-42715 after an intravenous administration of 20 mg/kg in rabbit was undetectable after 1 hour.
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PMID:SYN-1012: a new beta-lactamase inhibitor of penem skeleton. 918 63

One hundred and three strains of Neisseria gonorrhoeae isolated from a periurban STD clinic in The Gambia were studied for antimicrobial susceptibility, plasmid profile, and serogroup using standard procedures. Seventy-nine (77%) were penicillinase producers (PPNG) and fully resistant to penicillin (MIC > or = 8 mg/l). One isolate showed chromosomally induced resistance to penicillin (MIC 2 mg/l). None of the isolates was sensitive to tetracycline; 16 (16%) showed intermediate resistance (MICs 1-8 mg/l) and 87 (84%) showed high-level plasmid-mediated resistance (TRNG) (MICs > 10 mg/l). This is the first report of TRNG in The Gambia. Only 6 (6%) strains were fully sensitive to trimethoprim-sulphamethoxazole (MIC < 8 mg/l); 78 (76%) showed intermediate level resistance (MICs 8-16 mg/l) and 19 (18%) were fully resistant (MIC > 32 mg/l). Indications of an increase in MIC to ciprofloxacin and ceftriaxone were found in 6 (6%) and 1 (1%) strains, respectively, although all remained fully sensitive (MICs 0.004-0.03 mg/l and 0.001-0.015 mg/l). All PPNG and TRNG strains carried the 3.2 MDa and 25.2 MDa plasmids, respectively. All isolates carried the 2.6 MDa cryptic plasmid and 9 (3 PPNG and 6 non-PPNG) carried the 24.5 MDa conjugative plasmid. Forty-four (43%) strains were typed group W1, 58 (56%) W11/111 and 1 had cross-reacting antigens. Because PPNG are frequently encountered and high-level TRNG is now prevalent, the newer cephalosporins and quinolones must now be considered as first-line drugs for the treatment of gonorrhoea in The Gambia.
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PMID:Increasing prevalence of penicillinase-producing Neisseria gonorrhoeae and the emergence of high-level, plasmid-mediated tetracycline resistance among gonococcal isolates in The Gambia. 921 98

The survey carried on 579 patients of both sexes, consulting for genital discharges (spontaneous or referred), showed that in 61.1% men cases, STD agents were isolated (Neisseria gonorrhoeae 51.5%) and 64.4% in women cases (Gardnerella vaginalis 24%, Candida albicans 20%. Trichomonas vaginalis 14%). 17% of Neisseria gonorrhoeae strains were penicillinase-producing (PPNG).
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PMID:[The microbial etiology of genital discharges in Nouakchott, Mauritania]. 928 58

Serratia fonticola CUV produces two isoenzymes (forms I and II) with beta-lactamase activity which were purified by a five-step procedure. The isoenzymes had identical kinetic parameters and isoelectric point (pI = 8.12). They were characterized by a specific activity towards benzylpenicillin of 1650 U/mg. The beta-lactamase hydrolyzed benzylpenicillin, amoxycillin, ureidopenicillins, first- and second-generation cephalosporins. Carboxypenicillins and isoxazolylpenicillins were hydrolyzed to a lesser extent. Towards cefotaxime and ceftriaxone (third-generation cephalosporins), the S. fonticola enzyme exhibited catalytic efficiencies much higher than those of MEN-1 and extended-spectrum TEM derivative beta-lactamases. The beta-lactamase from S. fonticola was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam. The purified isoenzymes were digested by trypsin, endoproteinase Asp-N and chymotrypsin. Amino acid sequence determinations of the resulting peptides allowed the alignment of 267 amino acid residues (Swiss-Prot, accession number P 80545) for form I beta-lactamase. Form II is five residues shorter than form I at its N-terminus. From amino acid sequence comparisons, S. fonticola CUV beta-lactamase was found to share more than 69.3% identity with the chromosomally encoded beta-lactamases of Klebsiella oxytoca, Proteus vulgaris, Citrobacter diversus and the plasmid-mediated enzymes MEN-1 and Toho-1. Therefore, the oxyimino cephalosporin-hydrolyzing beta-lactamase of S. fonticola belongs to Ambler's class A. Contribution of the serine at ABL 237 in the broad-spectrum activity of these beta-lactamases is discussed.
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PMID:Characterization and amino acid sequence analysis of a new oxyimino cephalosporin-hydrolyzing class A beta-lactamase from Serratia fonticola CUV. 930 Aug 9

Klebsiella oxytoca strain HB60 is highly resistant to cefoperazone and aztreonam (MICs = 128 mg/L). It produces a chromosomally encoded beta-lactamase of pI 5.7 which was highly efficient against penicillins, first-generation cephalosporins and cefoperazone, a non-oxyimino third-generation cephalosporin. Aztreonam and oxyimino broad-spectrum cephalosporins were less good substrates. The beta-lactamase activity was susceptible to inhibition by clavulanic acid (IC50 = 1 microM). The enzyme purified to homogeneity had a specific activity towards benzylpenicillin of 3670 U/mg. The 263 amino acid residues of the protein were sequenced by Edman degradation of proteolytic peptides. The beta-lactamase was shown to belong to the OXY-2 group as it had only one amino acid substitution (Asn for Asp at ABL position 197) compared with the beta-lactamase (pI 5.2) from the aztreonam-susceptible K. oxytoca strain SL911 and two substitutions (Ala223 for Val and Asp255 for Asn) compared with the beta-lactamase (pI 6.4) from the aztreonam-resistant K. oxytoca strain D488. These three OXY-2-group enzymes behave in the same way towards beta-lactam antibiotics. The variability in the resistance of these K. oxytoca strains would thus seem to be due to variation in the level of production of the beta-lactamases rather than to structural alteration of the enzymes.
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PMID:Characterization and amino acid sequence of the OXY-2 group beta-lactamase of pI 5.7 isolated from aztreonam-resistant Klebsiella oxytoca strain HB60. 946 29

Tetracycline resistant Neisseria gonorrhoeae (TRNG) contain a 25.2 MDa TetM plasmid encoding a 68 KDa cytoplasmic protein which confers high-level tetracycline resistance. The aim of this study was to subtype all TRNG isolated in Scotland between 1992 and 1998. Subtyping was performed by a polymerase chain reaction (PCR) assay which characterizes the TetM plasmid as either the Dutch variant (443 base pair product) or the American variant (777 base pair product). Of the 78 TRNG isolates, 35 were the American variant and 43 were the Dutch variant. TRNG were distributed amongst 30 serovar/auxotype classes, the most common being 1A6/NR (11.5%), 1A6/P (14.1%) and 1B4/NR (14.1%). The country where infection was acquired was known for 36 of the 46 TRNG strains isolated between 1996 and 1998. All infections acquired in Asia and South America were the Dutch variant whereas all infections acquired in Africa were the American variant. A penicillinase plasmid was present in 66% (23/35) of the American variant TRNG compared with 51% (22/43) of the Dutch variant: the 3.2 MDa penicillinase plasmid was found in 87% of the American variant TRNG whereas the 4.4 MDa penicillinase plasmid was found in 68% of the Dutch variant TRNG. We conclude that subtyping of TRNG by PCR is a useful tool in studying the epidemiology of gonococcal infection due to plasmid-mediated resistant isolates.
Int J STD AIDS 1999 Oct
PMID:Subtyping of high-level plasmid-mediated tetracycline resistant Neisseria gonorrhoeae isolated in Scotland between 1992 and 1998. 1058 30


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