Tn916 family conjugative transposons and dissemination of antimicrobial resistance determinants.

Abstract

The widespread use of broad-spectrum antimicrobial agents poses a significant challenge to bacteria pathogenic for humans, a challenge that has been answered by the acquisition and spread of a variety of antimicrobial resistance determinants. Bacterial resistance to antibiotics results from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. Resistance to some antimicrobials or classes of antimicrobials, notably, rifampin or the fluoroquinolones, occurs primarily through point mutations and is not transferable. Other forms of resistance, such as multiple antibiotic resistance efflux systems and inducible β-lactamase-mediated resistance, result from regulatory mutations in normal cellular processes and are also not transferable. For many bacteria-antibiotic combinations, however, such intrinsic mechanisms of resistance are not available, so resistance genes must be imported. To accomplish this end, bacteria use a complex array of mechanisms to share and disseminate useful resistance determinants. Mechanisms frequently cited as potentially important for the dissemination of antibacterial resistance determinants include natural transformation (penicillin resistance in Streptococcus pneumoniae and Neisseria spp.) (16, 60), bacteriophage-mediated transduction (β-lactamase-mediated penicillin resistance in staphylococci) (33), and plasmid- or transposon-mediated conjugation (ampicillin resistance in members of the family Enterobacteriaceae, tetracycline resistance in enterococci, and many others) (3, 20). With the widespread availability of techniques for analyzing the molecular genetics of bacterial pathogens, understanding of the role of transposons in the dissemination of antimicrobial resistance has expanded significantly. Among the more interesting and important classes of transposons are the conjugative transposons. As their name implies, conjugative transposons are mobile elements that possess the genetic machinery to facilitate their own transfer between bacterial cells. Several prototypes of conjugative transposons have been described. Conjugative transposons encoding the tet(Q) tetracycline resistance determinants are widespread in clinical Bacteroides isolates and have been the subject of several recent reviews (54, 55). Tn5276-like transposons are large (70- to 80-kb) elements that encode genes for nisin production (44, 45). These elements have not been shown to encode antimicrobial resistance determinants, appear to be restricted to lactococci, and will not be addressed further in this minireview. The present minireview focuses on the Tn916 and Tn1545 family of conjugative transposons that predominates in clinically important gram-positive bacteria. The basic mechanisms of movement of these transposons have recently been reviewed (57). The present work focuses on recent developments in the basic science of conjugative transposons and more specifically on the actual and potential role of these elements in the dissemination of important resistance determinants in pathogenic bacteria.