Plasmid-mediated resistance to β-lactam antibiotics in Gram-negative bacteria: the role of in-vivo recyclization reactions in plasmid evolution

Over 20 different plasmid-encoded β-lactamases have so far been discovered. This paper considers genetic mechanisms by which β-lactamase genes encoded by Plasmids are disseminated across generic boundaries. Particular emphasis is placed on the evolution of plasmids carrying all or part of Tn3 and encoding TEM-1 β-lactamase in Haemophilus and Neisseria species. Examples of the acquisition of broad host range plasmids carrying Tn3 sequences and of rescue of transposon sequences to indigenous plasmids or to the host chromosome have been found in these two genera. Studies on nonconjugative β-lactamase plasmids in Neisseria and Haemophilus are consistent with the evolution of a family of plasmids originating from the insertion of Tn3 into an indigenous progenitor plasmid. A series of subsequent insertional and deletional events, most probably occurring as a consequence of genetic transfer, have given rise to the existing group of small, closely related ampicillin-resistance plasmids found currently in these genera. A general model for deletional and other rearrangements caused by recombinational recyclization during the evolution of resistance plasmids is described.