Susceptibility of streptococci to newer tetracyclines and cephalosporins and to other antimicrobial agents.

Two hundred and thirty-nine strains of Streptococcus including 71 strains of Group A, 81 strains of Group B, 69 strains of enterococci, and 18 strains of S. pneumoniae were tested against 12 antimicrobial agents using an agar dilution method. Cefamandole was the most active cephalosporin tested. Doxycycline and minocycline were more active than tetracycline, although the tetracyclines were considerably less inhibitory than the cephalosporins. Regression line analysis of zones of inhibition versus minimal inhibitory concentration values for tetracycline and minocycline showed the tetracycline disc to be unacceptable for predicting the susceptibility of the Group A Streptococcus to minocycline. Minimal inhibitory concentrations for clindamycin, erythromycin, chloramphenicol, nitrofurantoin, and spectinomycin are also given.

Control of expression of the Tn10-encoded tetracycline resistance genes. Equilibrium and kinetic investigation of the regulatory reactions.

The transposon Tn10-encoded TET repressor controls the expression of tetracycline resistance as well as its own synthesis. The antibiotic tetracycline functions as an inducer for both genes, which are transcribed in divergent directions from a common start area. The interaction of the TET repressor with the regulatory sequence of the tetracycline resistance operon is investigated by equilibrium and kinetic methods. The wild-type control sequence contains two nearly identical operators separated by only ten base-pairs. A deletion mutant lacking one of the operators is constructed by controlled digestion with exonuclease Bal31. It serves to prove that the two TET operators are each occupied by a TET repressor dimer in the wild-type tet operon regulatory sequence. The association constants are approximately identical for both operators between 10(12) and 10(13) M-1 as derived from kinetic data. The half-life of the TET repressor--tet operator complex is 12 minutes when competed with tet operator DNA and two minutes when competed with the inducer tetracycline. The dissociation of the repressor--operator complex has no apparent activation enthalpy but has an activation entropy of -320 J/mol K, indicating the involvement of solvent or counterion condensation. The dissociation rate constant of the tetracycline--TET repressor complex depends strongly on temperature. The activation enthalpy is 160 kJ/mol, indicating extremely strong binding of the drug. This result is discussed with respect to the necessary sensitivity of a regulated resistance gene. The native structure of the TET repressor is a dimer, as demonstrated by molecular exclusion chromatography. The elution behavior of the TET repressor--tetracycline complex indicates clearly that the repressor--inducer complex remains a dimer. The results are discussed with respect to the regulatory functions of the components.

Characterisation of Yersinia species isolated from a kennel and from cattle and pig farms.

Between April 1984 and November 1986, 126 faeces samples were collected from puppies and bitches in a kennel and examined for Yersinia species; 45 (35.7 per cent) of them were positive. Thirty-eight isolates were Y enterocolitica, five were Y frederiksenii and two were Y intermedia. Twenty-one of the Y enterocolitica isolates belonged to serogroup 0:3 and 17 of these were L-sorbose negative; all these isolates were from puppies. One strain of Y frederiksenii and all the L-sorbose-negative Y enterocolitica serogroup 0:3 isolates were resistant to antimicrobial agents and showed four different patterns of resistance (ampicillin, cephalothin and tetracycline; ampicillin, cephalothin, streptomycin and tetracycline; ampicillin, chloramphenicol, cephalothin, streptomycin and sulfathiazole; and ampicillin, chloramphenicol, cephalothin, streptomycin, sulfathiazole and tetracycline. In January 1986, investigations were conducted on a cattle farm and a pig farm close to the kennel. Of 19 bovine faeces samples 11 (57.8 per cent) were positive for Yersinia species; eight yielded Y enterocolitica and four yielded Y frederiksenii. None of the Y enterocolitica isolates belonged to serogroup 0:3. Of 20 porcine faeces samples eight (40 per cent) were positive for Yersinia species; all eight yielded Y enterocolitica and four also yielded Y pseudotuberculosis. Two of the isolates of Y frederiksenii and two of the isolates of Y enterocolitica from the farms had the following resistance patterns: ampicillin, cephalothin and streptomycin; ampicillin, streptomycin and tetracycline; ampicillin, chloramphenicol, cephalothin, streptomycin, trimethoprim-sulphamethoxazole and tetracycline; and ampicillin, chloramphenicol, cephalothin, streptomycin, sulphatiazole, trimethoprim-sulphamethoxazole and tetracycline.(ABSTRACT TRUNCATED AT 250 WORDS)

Tetracyclines inhibit protein glycation in experimental diabetes.

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi-fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.