Different Pathways to Acquiring Resistance Genes Illustrated by the Recent Evolution of IncW Plasmids

Departamento de Biología Molecular e Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC-IDICAN, C. Herrera Oria s/n, 39011 Santander, Spain.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 05/2008; 52(4):1472-80. DOI: 10.1128/AAC.00982-07
Source: PubMed


DNA sequence analysis of five IncW plasmids (R388, pSa, R7K, pIE321, and pIE522) demonstrated that they share a considerable
portion of their genomes and allowed us to define the IncW backbone. Among these plasmids, the backbone is stable and seems
to have diverged recently, since the overall identity among its members is higher than 95%. The only gene in which significant
variation was observed was trwA; the changes in the coding sequence correlated with parallel changes in the corresponding TrwA binding sites at oriT, suggesting a functional connection between both sets of changes. The present IncW plasmid diversity is shaped by the acquisition
of antibiotic resistance genes as a consequence of the pressure exerted by antibiotic usage. Sequence comparisons pinpointed
the insertion events that differentiated the five plasmids analyzed. Of greatest interest is that a single acquisition of
a class I integron platform, into which different gene cassettes were later incorporated, gave rise to plasmids R388, pIE522,
and pSa, while plasmids R7K and pIE321 do not contain the integron platform and arose in the antibiotic world because of the
insertion of several antibiotic resistance transposons.

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Available from: Christopher M Thomas, Dec 13, 2013
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    • "Integrons possess a site-specific recombination system able to integrate, rearrange, and express adaptive genes, including antibiotic resistance genes (Mazel, 2006; Partridge, 2011; Stokes and Gillings, 2011; Moura et al., 2012). These genetic platforms are ancient structures (several hundred million years old) that were already involved in the initial outbreaks of antibiotic resistance in the 1950s (Liebert et al., 1999; Mazel, 2006; Revilla et al., 2008). The same type of integrons, now carrying a diversity of antibiotic resistance genes, are preserved in the current bacterial world, and have installed themselves in natural environments along extended periods of time (Petrova et al., 2011; Stokes and Gillings, 2011; Stalder et al., 2012). "
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    ABSTRACT: Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level population biology of bacteria. Antibiotics produced by natural organisms play a role in their interactions shaping the lifestyle and homeostasis of bacterial pop-ulations and communities (Waksman, 1961; Davies, 2006; Fajardo and Martínez, 2008; Aminov, 2009). Such interactions might be of antagonistic nature as the production of antibiotics serves to inhibit other bacterial populations. Inhibition does not necessarily intend to kill competitive bacterial organisms, but rather prevent undesirable local overgrowth of partners in shared ecosystems. The diffusion of antibiotics in the environment assures an "exclu-sive zone" at a certain distance from the producer population. At the borders of such a zone, the potentially competing organisms are confronted with very low antibiotic concentrations, proba-bly sufficient to decrease their growth rate, but not to kill the competing neighbor. In this sense, it is highly possible that the production of antagonistic (allelopathic) substances by microor-ganisms has more a defensive than offensive nature (Chao and Levin, 1981). In addition, mutual inhibition is frequently desir-able for the maintenance of healthy species diversity in a particular ecosystem (Czárán et al., 2002; Becker et al., 2012; Cordero et al., 2012). It is of note that natural antibiotic production, decreasing the growth rate of the competing population, not only restricts its local predominance, but also assures that this population is preserved, as antibiotic-promoted cessation of growth is a highly effective system to avoid antibiotic killing. However, the production of natural antibiotics might only have functions unrelated with inter-bacterial antagonisms. Antagonism might arise in particular contexts as a side-effect of cell-to-cell signaling effects resulting in self-regulation of growth, viru-lence, sporulation, motility, mutagenesis, SOS stress response, phage induction, transformation, lateral gene transfer, intra-chromosomal recombination, or biofilm formation (Goh et al., 2002; Ubeda et al., 2005; Linares et al., 2006; Yim et al., 2007; Martínez, 2008; Couce and Blázquez, 2009; Kohanski et al., 2010; Allen et al., 2011; Baharoglu and Mazel, 2011; Pedró et al., 2011; Looft and Allen, 2012; Looft et al., 2012). Natural antibiotic resistance modulates the effect of the natural production of antibiotics, so antibiotic production and antibiotic resistance act as two complementary sides of the same process
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    • "All putative plasmids were compared to each other using MUMmer. In order to determine whether our confirmed plasmids or previously sequenced Providencia plasmids [25-27] were present but undetected in the remaining sequences from this study, we constructed a BLAST database of all of the reads from the Roche/454 sequencing of each individual species and searched for reads matching each Providencia plasmid using BLAST+ (version 2.2.25). Four previously identified Providencia plasmids were used as query sequences: pDIJ09-518a [GenBank:HQ834472.1], "
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    ABSTRACT: Background Comparative genomics can be an initial step in finding the genetic basis for phenotypic differences among bacterial strains and species. Bacteria belonging to the genus Providencia have been isolated from numerous and varied environments. We sequenced, annotated and compared draft genomes of P. rettgeri, P. sneebia, P. alcalifaciens, and P. burhodogranariea. These bacterial species that were all originally isolated as infections of wild Drosophila melanogaster and have been previously shown to vary in virulence to experimentally infected flies. Results We found that these Providencia species share a large core genome, but also possess distinct sets of genes that are unique to each isolate. We compared the genomes of these isolates to draft genomes of four Providencia isolated from the human gut and found that the core genome size does not substantially change upon inclusion of the human isolates. We found many adhesion related genes among those genes that were unique to each genome. We also found that each isolate has at least one type 3 secretion system (T3SS), a known virulence factor, though not all identified T3SS belong to the same family nor are they in syntenic genomic locations. Conclusions The Providencia species examined here are characterized by high degree of genomic similarity which will likely extend to other species and isolates within this genus. The presence of T3SS islands in all of the genomes reveal that their presence is not sufficient to indicate virulence towards D. melanogaster, since some of the T3SS-bearing isolates are known to cause little mortality. The variation in adhesion genes and the presence of T3SSs indicates that host cell adhesion is likely an important aspect of Providencia virulence.
    BMC Genomics 11/2012; 13(1):612. DOI:10.1186/1471-2164-13-612 · 3.99 Impact Factor
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    • "The propagation module (coding for the genes involved in conjugation) is divided into two colors, because it contains a module for conjugative DNA processing (MOB, for plasmid mobilization) and a second one responsible for the synthesis of the type IV secretion system that constitutes the conjugation channel (MPF, for mating pair formation). Further details of the genetic constitution of these plasmids can be found in Fernandez-Lopez et al. (2006) and Revilla et al. (2008) "
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    ABSTRACT: Plasmids contain a backbone of core genes that remains relatively stable for long evolutionary periods, making sense to speak about plasmid species. The identification and characterization of the core genes of a plasmid species has a special relevance in the study of its epidemiology and modes of transmission. Besides, this knowledge will help to unveil the main routes that genes, for example antibiotic resistance (AbR) genes, use to travel from environmental reservoirs to human pathogens. Global dissemination of multiple antibiotic resistances and virulence traits by plasmids is an increasing threat for the treatment of many bacterial infectious diseases. To follow the dissemination of virulence and AbR genes, we need to identify the causative plasmids and follow their path from reservoirs to pathogens. In this review, we discuss how the existing diversity in plasmid genetic structures gives rise to a large diversity in propagation strategies. We would like to propose that, using an identification methodology based on plasmid mobility types, we can follow the propagation routes of most plasmids in Gammaproteobacteria, as well as their cargo genes, in complex ecosystems. Once the dissemination routes are known, designing antidissemination drugs and testing their efficacy will become feasible. We discuss in this review how the existing diversity in plasmid genetic structures gives rise to a large diversity in propagation strategies. We would like to propose that, by using an identification methodology based on plasmid mobility types, we can follow the propagation routes of most plasmids in ?-proteobacteria, as well as their cargo genes, in complex ecosystems.
    FEMS microbiology reviews 06/2011; 35(5):936-56. DOI:10.1111/j.1574-6976.2011.00291.x · 13.24 Impact Factor
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