Nature and Interactions of the Genetic Elements Governing Penicillinase Synthesis in Staphylococcus aureus

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Novick, Richard P. (The Rockefeller Institute, New York, N.Y.), and Mark H. Richmond. Nature and interactions of the genetic elements governing penicillinase synthesis in Staphylococcus aureus. J. Bacteriol. 90:467–480. 1965.—It has been found previously that penicillinase-producing strains of Staphylococcus aureus each harbor an extrachromosomal element, or plasmid, which apparently carries all the genetic information necessary for penicillinase synthesis. These plasmids behave in a manner consistent with their being small chromosomelike structures in that they comprise linkage groups containing several markers and in that they undergo such genetic events as mutation, segregation, and recombination. There is currently no evidence for conjugal cell-cell transfer of the plasmids or for a state of stable integration into the staphylococcal chromosome. A certain amount of variability has been encountered among the penicillinase plasmids harbored by different staphylococcal strains. It has been found that: (i) there are at least three molecular variants of the enzyme itself; (ii) most, but not all, of the penicillinase plasmids carry a genetic determinant of resistance to mercuric ion; (iii) plasmids carried by a very small number of the strains bear a determinant of resistance to erythromycin; (iv) the plasmids determine the fraction of penicillinase excreted into the medium during growth, and this also varies from strain to strain. The penicillinase plasmids appear to behave as integral genetic structures. The entire known linkage group is transduced intact, and is occasionally lost completely as a spontaneous occurrence during the growth of the organisms. Rarely, the plasmid markers dissociate during transduction, resulting in transduced clones which have inherited only a part of the plasmid linkage group. Similarly, dissociation occurs as a spontaneous event during normal growth, also resulting in rare clones which appear to have lost one or more but not all of the plasmid markers. When crosses are performed between two plasmid-harboring strains, a plasmid heterozygote is formed. In most cases, this persists for only one or a few cell divisions before segregating, with or without the formation of recombinant plasmids. In two instances thus far observed, the heterozygote persists as a stable plasmid heterodiploid, in which the continued presence of both plasmids can be readily demonstrated. The fate of the heterozygote, i.e., early segregation or persistence as a heterodiploid, depends upon which particular pair of plasmids is involved in the cross. This observation has led to the hypothesis of a plasmid-linked determinant of plasmid compatibility. A pair of plasmids is considered compatible if it can form a stable heterodiploid, incompatible if it cannot.

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