Bacteria can resist macrolide, lincosamide, and streptogramin (MLS) antibiotics enzymically by alteration of the target site or detoxification of the antibiotic. N6-dimethylation of adenine in 23 S ribosomal RNA confers resistance to M, L, and S B-type (MLSB) antibiotics. Investigation, by DNA annealing, of the relationship between the genes specifying this resistance mechanism from Streptococcus (groups A,B,D, and H, and pneumoniae), Staphylococcus aureus, Bacillus licheniformis, Bacteroides fragilis, Lactobacillus casei, and Streptomyces erythreus indicated substantial sequence diversity among the MLSB resistance (R) determinants. A minimum of four distinct classes of MLSB R determinants could be defined: classes A and B for the Gram-positive cocci (streptococci pmeumococci and staphylococci), class C for B. licheniformis, and class D for Bact. fragilis. These data do not support the hypothesis that the R determinants were acquired recently from a single common origin and suggest an easy exchange of genetic information among the Gram-positive cocci. The genetic classes do not correlate with differences in phenotypic expression or in regulation (inducibility or constitutivity) of resistance towards MLSB antibiotics. Inactivation of the drug confers resistance to M and/or L and/or S or SA or SB antibiotics and has been detected in strains of Streptococcus, Staph. aureus, Lactobacillus, C. perfringens, Streptomyces, and recently in the Gram-negative organism Escherichia coli. We have cloned and sequenced a DNA fragment conferring high level resistance (MIC greater than 2 g/l) to erythromycin by hydrolysis of the antibiotic. The distribution of this 'new' character in enterobacteria isolated from human faeces was studied by colony hybridization using an intragenic probe. The gene for the erythromycin esterase was detected in numerous strains of E. coli belonging to various biotypes, in Klebsiella pneumoniae, Enterobacter agglomerans, and in one 'coliform'. Moreover, our results indicated the existence of at least two classes of genes specifying resistance to erythromycin by inactivation of the antibiotic in enterobacteria.
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