Conjugative transfer in the dissemination of beta-lactam and aminoglycoside resistance

Abstract

The dissemination of antibiotic resistance among pathogenic bacteria can be attributed largely to conjugative DNA transfer. The general category of conjugative transfer includes both bacterial plasmid conjugation and the transfer of nonreplicative conjugative transposons. Prototypes for these two systems are the plasmid RK2 and the conjugative transposon Tn916. To address the long-term problem of the increasing prevalence and severity of antibiotic resistance, strategies aimed against conjugative transfer are needed, but their development will require a greater understanding of conjugative resistance gene acquisition. Overviews of the two conjugative transfer systems are presented, to summarize and compare current concepts. Observations regarding transfer of conjugative transposons is consistent with the prevailing model for plasmid conjugation, that is, by the transfer of a single-stranded DNA molecule from the donor to the recipient bacterium, and the generation of the single strand by rolling circle DNA replication. The relevance of vegetative plasmid replication and host range to the spread of multiple drug resistance is discussed, and clinical examples of conjugative transfer of multiple antibiotic resistance illustrate the severity of the current situation. Possible directions, traditional and innovative, are offered to address the conjugative transfer problem in drug resistance, and potentially to break the cycle of antibiotic development followed by the bacterial resistance gene acquisition.

Aminoglycosides: Mechanisms of Action and Resistance

“…Since the report of the fi rst β-lactamase-producing organism in 1983, β-lactam resistance is often associated with high-level resistance to aminoglycosides. In fact, genes encoding β-lactamases are usually carried on transferable plasmids that often also contain aminoglycoside resistance genes (119,121,133,134). The resulting cross-resistance can make serious enteroccocal infections, such as endocarditis, extremely diffi cult to treat.…”

“…The rapid dissemination of aminoglycoside resistance among pathogenic organisms has been largely attributed to conjugation of plasmids and non-replicative transposons among bacteria (119,120,123,124). A clinical example of the ongoing importance of conjugative plasmid transfer on resistance to aminoglycosides is the shocking case of untreatable and fatal neonatal septicemia mediated by Klebsiella pneumonia EK105, which carries a mobile plasmid encoding resistance to amikacin, ampicillin chloramphenicol, kanamycin, streptomycin, tobramycin, netilmicin, oxacillin, gentamicin, and mezlocillin (125).…”

“…The rapid spread of drug resistance among pathogenic bacteria is usually attributed to horizontal gene transfer since the development of antimicrobial resistance by mutational changes is a relatively slow process (119,120).…”

Transformation of isolated mammalian mitochondria by bacterial conjugation

“…Because conjugation is a relatively gentle process, we reasoned that this type of procedure would enable us to transfer large DNA constructs into mitochondria without damaging the structural integrity of the mitochondria. Although conjugation typically involves bacterium-to-bacterium DNA transfer via pili, the conjugation process is driven entirely by molecular machinery in the donor cell (13) and so an amazingly broad range of cell types can serve as the DNA recipient, including yeast (14,15), plants (16) and mammalian cells (17,18). …”

Autoinhibitory Regulation of TrwK, an Essential VirB4 ATPase in Type IV Secretion Systems

“…Conjugative T4SSs are used by bacteria to mediate the transfer of DNA and proteins to conjugation recipient cells, resulting in the widespread transmission of antibiotic resistance genes among pathogenic bacteria (3,4). Other T4SSs are used by several plant and human pathogens, such as Agrobacterium tumefaciens, Helicobacter pylori, Bordetella pertusis, Brucella suis, etc., to deliver virulence-related effectors to eukaryotic target cells (5)(6)(7).…”