Tobramycin, amikacin, sissomicin, and gentamicin resistant Gram-negative rods.
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Sensitivities to gentamicin, sissomicin, tobramycin, and amikacin were compared in 196 gentamicin-resistant Gram-negative rods and in 212 similar organisms sensitive to gentamicin, mainly isolated from clinical specimens. Amikacin was the aminoglycoside most active against gentamicin-resistant organisms, Pseudomonas aeruginosa, klebsiella spp, Escherichia coli, Proteus spp, Providencia spp, and Citrobacter spp being particularly susceptible. Most of the gentamicin-resistant organisms were isolated from the urine of patients undergoing surgery. Gentamicin was the most active antibiotic against gentamicin-sensitive E coli, Proteus mirabilis, and Serratia spp. Pseudomonas aeruginosa and other Pseudomonas spp were most susceptible to tobramycin. (+info)
UK-18892, a new aminoglycoside: an in vitro study.
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UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differences were relatively minor. UK-18892 was about twice as active as amikacin against gentamicin-susceptible strains of Pseudomonas aeruginosa. Both amikacin and UK-18892 were equally active against gentamicin-resistant strains of P. aeruginosa. There were no appreciable differences in the activity of UK-18892 and amikacin against Enterobacteriaceae and Staphylococcus aureus. Cross-resistance between these two antimicrobials was also apparent. (+info)
A single membrane-embedded negative charge is critical for recognizing positively charged drugs by the Escherichia coli multidrug resistance protein MdfA.
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The nature of the broad substrate specificity phenomenon, as manifested by multidrug resistance proteins, is not yet understood. In the Escherichia coli multidrug transporter, MdfA, the hydrophobicity profile and PhoA fusion analysis have so far identified only one membrane-embedded charged amino acid residue (E26). In order to determine whether this negatively charged residue may play a role in multidrug recognition, we evaluated the expression and function of MdfA constructs mutated at this position. Replacing E26 with the positively charged residue lysine abolished the multidrug resistance activity against positively charged drugs, but retained chloramphenicol efflux and resistance. In contrast, when the negative charge was preserved in a mutant with aspartate instead of E26, chloramphenicol recognition and transport were drastically inhibited; however, the mutant exhibited almost wild-type multidrug resistance activity against lipophilic cations. These results suggest that although the negative charge at position 26 is not essential for active transport, it dictates the multidrug resistance character of MdfA. We show that such a negative charge is also found in other drug resistance transporters, and its possible significance regarding multidrug resistance is discussed. (+info)
Effects of chronic administration of kanamycin on conditioned suppression to auditory stimulus in rats.
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The conditioned suppression technique was employed to study the ototoxic effects of chronic administration of the antibiotic, kanamycin. Lever pressing behavior for food reinforcement of rats was suppressed in the presence of an auditory stimulus (sound) or visual stimulus (light) that had been previously paired with electric shocks. Repeated administration of kanamycin at the dose of 400 mg/kg/day for more than 50 days significantly attenuated the conditioned suppression to auditory stimulus but did not attenuate the conditioned suppression to visual stimulus. This finding suggests that the attenuating effect of chronic administration of kanamycin on conditioned suppression to auditory stimulus can be interpreted in terms of the selective action of the drug on the auditory system. (+info)
Experimental enteropathy in athymic and euthymic rats: synergistic role of lipopolysaccharide and indomethacin.
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The aim of this study was to investigate the immunologic and microbiological bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen-free (SPF) rats were reared under conventional or SPF conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously described ulcer index and tissue myeloperoxidase activity. Both euthymic and athymic nude rats developed intestinal ulcers to the same degree under conventional conditions but no or minimal ulcer under SPF conditions. Pretreatment of conventional rats with intragastric kanamycin sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a dose-dependent fashion. Interestingly, when lipopolysaccharide was injected intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in these rats in a dose-dependent manner. We confirmed that kanamycin decreased the number of gram-negative bacteria and endotoxin concentration of the small intestine in a dose-dependent fashion. These results indicate that indomethacin enteropathy is bacteria dependent and does not require a T cell function. Synergy between indomethacin and bacterial lipopolysaccharide may play a major role in this enteropathy. (+info)
CspA, CspB, and CspG, major cold shock proteins of Escherichia coli, are induced at low temperature under conditions that completely block protein synthesis.
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CspA, CspB, and CspG, the major cold shock proteins of Escherichia coli, are dramatically induced upon temperature downshift. In this report, we examined the effects of kanamycin and chloramphenicol, inhibitors of protein synthesis, on cold shock inducibility of these proteins. Cell growth was completely blocked at 37 degrees C in the presence of kanamycin (100 microgram/ml) or chloramphenicol (200 microgram/ml). After 10 min of incubation with the antibiotics at 37 degrees C, cells were cold shocked at 15 degrees C and labeled with [35S]methionine at 30 min after the cold shock. Surprisingly, the synthesis of all these cold shock proteins was induced at a significantly high level virtually in the absence of synthesis of any other protein, indicating that the cold shock proteins are able to bypass the inhibitory effect of the antibiotics. Possible bypass mechanisms are discussed. The levels of cspA and cspB mRNAs for the first hour at 15 degrees C were hardly affected in the absence of new protein synthesis caused either by antibiotics or by amino acid starvation. (+info)
Identification of Haemophilus influenzae Rd transformation genes using cassette mutagenesis.
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Genes required for natural transformation of Haemophilus influenzae Rd were identified by a cassette mutagenesis protocol consisting of the following steps: random insertional mutagenesis, phenotypic screening, sequencing of genome sequence tags from the DNA flanking the insertion in the selected mutants and comparison of genome sequence tags to genomic sequence data. The cassette mutagenesis screen for transformation genes resulted in five distinct mutant classes, two of which have been identified in previous studies. Insertions in the three newly identified loci interrupted genes with predicted protein products homologous to a type IV pilin-like protein biogenesis operon, drug-efflux transporters and a phospholipid-biosynthesis enzyme. The most significant finding of this screen is the requirement for type IV pilin-like proteins in genetic transformation of H. influenzae. These surface structures are utilized for DNA uptake in a number of Gram-positive and Gram-negative bacteria, and appear to be the common component among the systems for DNA binding. (+info)
In vitro comparison of kanamycin, kanendomycin, gentamicin, amikacin, sisomicin, and dibekacin against 200 strains of Pseudomonas aeruginosa.
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The antimicrobial activity of kanamycin, kanendomycin, gentamicin, amikacin, sisomicin, and dibekacin against 200 strains of Pseudomonas aeruginosa was compared. Dibekacin was found to be the most active against the tested organisms, whereas the other aminoglycoside antibiotics fell in the following order of diminishing antibacterial potency: amikacin, sisomicin, gentamicin, kanendomycin, and kanamycin. Seven strains showed high-level resistance to gentamicin (minimal inhibitory concentration, 400 mug/ml), and two of them were also resistant to amikacin and sisomicin (minimal inhibitory concentration, 75 mug/ml). The minimal inhibitory concentration of dibekacin for these seven strains was 0.625 mug/ml. (+info)