The Genetics of Tetracycline Resistance in Staphylococcus aureus

Abstract

Eighty-one strains of Staphylococcus aureus that appeared to be tetracycline resistant on the basis of a preliminary disc-diffusion test were examined for resistance to tetracycline and to the semi-synthetic tetracycline, minocycline. Minimum inhibitory concentration (m.i.c.) values for both drugs were determined after induction of the strains by growth for 2 h in sub-inhibitory concentrations of tetracycline. Forty-seven strains (58 %) had m.i.c. values for minocycline of 12-5 pg/ml or greater, and were considered to be minocycline resistant. An additional ten strains had m.i.c. values for minocycline of 3-125 to 6-25 ,ug/ml and were classified as low-level resistant strains. It appears, therefore, that a fairly high proportion of tetracycline-resistant strains isolated at the present time are resistant to concentrations of minocycline unattainable in vivo with the recommended dosage for this antibiotic (Frisk & Tunevall, 1969).Transductional analysis of the genetic determinants for tetracycline resistance revealed the existence of two types of resistance to high concentrations of tetracycline. Strains in the first category (A) were inducibly resistant to tetracycline but sensitive to minocycline; in these strains the resistance determinant was plasmid-borne. Strains in the second category (B) were resistant to both tetracycline and minocycline and had low induction ratios for tetracycline resistance ; the genetic determinant for resistance in these strains was chromosomal. In addition, certain strains in category A were found to carry a chromosomal gene controlling low-level resistance to tetracycline and minocycline. This low-level resistance to tetracycline was masked in the presence of the tetracycline plasmid but could be demonstrated after loss of the plasmid. The results suggest that more than one mechanism of resistance to tetracyclines may exist in staphylococci.

Induction of Tetracycline Resistance in Staphylococcus aureus in the Absence of Lipid Synthesis

“…The characteristics of plasmid-mediated tetracycline resistance in these bacteria are similar, in that resistance is usually inducible (Izaki, Kiuchi & Arima, 1966;Franklin, 1967;Sompolinsky et al 1970a Asheshov, 1975), and appears to result from decreased uptake of the antibiotic (Izaki et al 1966;Franklin, 1967;De Zeeuw, 1968;Sompolinsky et al 1g7oa;Avtalion et al 1971; Kuck & Forbes, 1973;Shipley & Olsen, 1974).…”

Occurrence of a nonplasmid-located determinant for gentamicin resistance in strains ofStaphylococcus aureus

“…In contrast to this, other chromosomally located resistance determinants in S. aureus are obviously bound to definite strains such as the determinants for resistance to oxytetracycline-minocycline (Asheshov, 1975;Witte & Diinnhaupt, 1982) and for methicillin resistance (Lacey, 1975). The spread of the chromosomal determinant for resistance to gentamicin is probably due to a special mechanism of a transductional transfer.…”

The Effect of Membrane-bound -Lactamase on Linoleic Acid Sensitivity in Staphylococcus aureus

“…However, the genetic determinants for tetracycline resistance can have a plasmid or chromosomal location in S . aureus (Lacey, 1973;Asheshov, 1975). The resistances are qualitatively different, since the plasmid gene confers inducible resistance to tetracycline but not to minocycline, whereas the chromosomal gene controls non-inducible resistance to both antibiotics.…”

“…Both these strains were originally isolated by Richmond (1963) after EMS mutagenesis of 8325(p15,,). Staphylococcus uureurr 31 10 and phage 85 were very kindly given by Dr E. H. Asheshov,and 8325Tet5,lo(N) was constructed by transduction of tetracycline resistance from strain 31 10 (chromosomal tetracycline resistance) into 8325(N) using phage 85 (Asheshov, 1975). The kinetics of this transduction were typical for a chromosomal gene in that the frequency was low with unirradiated phage but was stimulated by small doses of UV light (Arber, 1960;Asheshov, 1975).…”

“…Tetracycline could have caused sufficient damage to the tetracycline-resistant bacteria to produce the small increase in linoleic acid sensitivity, especially since there was a slight increase in the mean generation time of the tetracycline-treated cultures. Since the tetracycline resistance determined by chromosomal genes would appear to be noninducible (Lacey, 1973;Asheshov, 1975), it should be possible to use a chromosomal tetracycline-resistant mutant in an experiment to control for any deleterious effects of tetracycline exposure upon subsequent linoleic acid sensitivity. The genes determining the tetracycline resistance of S .…”