Spread and Persistence of Virulence and Antibiotic Resistance Genes: A Ride on the F Plasmid Conjugation Module

Abstract

The F plasmid or F-factor is a large, 100-kbp, circular conjugative plasmid of and was originally described as a vector for horizontal gene transfer and gene recombination in the late 1940s. Since then, F and related F-like plasmids have served as role models for bacterial conjugation. At present, more than 200 different F-like plasmids with highly related DNA transfer genes, including those for the assembly of a type IV secretion apparatus, are completely sequenced. They belong to the phylogenetically related MOBA group. F-like plasmids are present in enterobacterial hosts isolated from clinical as well as environmental samples all over the world. As conjugative plasmids, F-like plasmids carry genetic modules enabling plasmid replication, stable maintenance, and DNA transfer. In this plasmid backbone of approximately 60 kbp, the DNA transfer genes occupy the largest and mostly conserved part. Subgroups of MOBA plasmids can be defined based on the similarity of TraJ, a protein required for DNA transfer gene expression. In addition, F-like plasmids harbor accessory cargo genes, frequently embedded within transposons and/or integrons, which harness their host bacteria with antibiotic resistance and virulence genes, causing increasingly severe problems for the treatment of infectious diseases. Here, I focus on key genetic elements and their encoded proteins present on the F-factor and other typical F-like plasmids belonging to the MOBA group of conjugative plasmids.

Structural bases for F plasmid conjugation and F pilus biogenesis in Escherichia coli

“…cryoelectron tomography | DNA conjugation | type IV secretion | pilus | protein transport I n the 1940s, Lederberg and Tatum ushered in the era of bacterial genetics with reports of sexual "mating" orchestrated by the Escherichia coli F "fertility" factor (1). Bacterial sex, now termed conjugation, is widely recognized as a predominant mechanism underlying the rapid and widespread transmission of antibiotic resistance genes and the evolution of untreatable "superbugs" (2). Over the past seven decades, researchers have described many of the underlying regulatory and mechanistic features associated with horizontal gene transfer (3,4).…”

Phenotypic and genotypic profile of Enterobacteria resistant to beta-lactams

“…Drug resistance genes can be spread from one bacterium to another through various mechanisms such as plasmids, bacteriophages, naked DNA or transposons. Some transposons contain integronsmore complex transposons that contain a site for integrating different antibiotic resistance genes and other gene cassettes in tandem for expression from a single promoter (8).Bacterial conjugation is the most sophisticated form of horizontal gene transfer (HGT) in bacteria and provides a platform for the spread and persistence of antibiotic resistance and virulence genes (9). Beta-lactams are preferred because of their clinical efficacy and safety by virtue of their high selective toxicity (10).…”

Potentiation of curing by a broad-host-range self-transmissible vector for displacing resistance plasmids to tackle AMR

“…Therefore, the binding sites for the replication protein TrfA and binding of KorB protein to RK2 DNA may need to be configured correctly to achieve a level of supercoiling sufficient to activate key loci of the anti-F and anti-K cassettes. Since the anti-K cassette is basically the antisense RNA regulatory elements of the IncK replicon from R387 [31], if there is just one part of the anti-F cassette that needs to be potentiated, it seems most likely to be the FII replicon [10,11], since this has the greatest similarity to the IncK replication control region. This in turn points to the possibility that the different components of a plasmid's backbone maintenance functions may interact in a synergistic way to create the right genomic environment for optimal function of the plasmid's regulatory circuits, a general point about plasmid organisation not previously recognised [6].…”

“…Since F-like plasmids are the commonest plasmid types encountered among multi-resistant Enterobacteriaceae and can also carry virulence functions [10,11], it is important that anti-F pCURE plasmids can be adapted to displace all possible targets. To test this we chose pEK499 [36] which we found was not displaced by the anti-F cassette in pCURE2 and pCURE-F-307 (Table 1).…”

“…The work described here therefore uses a related, unidirectional approach where a reproductively unrelated vector displaces the target plasmid because it carries genetic regions which block all replication and addiction systems the target plasmid encodes. This is a complex task when target plasmids carry multiple replicons and PSK systems, as in the very common F-like plasmids of Enterobacteriaceae (Fig 2) [10,11,12]. Efficient displacement of the F-like plasmids pO157 [13,14], p1658/97 [15] and pKDSC50 [16], as well as F 0 prolac [17] was previously achieved using a high-copy number vector compatible with the target plasmid [12].…”