scholarly journals Evolution of satellite plasmids can stabilize the maintenance of newly acquired accessory genes in bacteria

2019 ◽  
Author(s):  
Xue Zhang ◽  
Daniel E. Deatherage ◽  
Hao Zheng ◽  
Stratton J. Georgoulis ◽  
Jeffrey E. Barrick
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Antibiotic Resistance Genes ◽  
New Host ◽  
Bacterial Populations ◽  
Evolutionary Pathway ◽  
Bacterial Gene ◽  
Accessory Genes ◽  
A Cell ◽  
Incq Plasmids

AbstractPlasmids play a principal role in the spread of antibiotic resistance and other traits by horizontal gene transfer in bacteria. However, newly acquired plasmids generally impose a fitness burden on a cell, and they are lost from a population rapidly if there is not selection to maintain a unique function encoded on the plasmid. Mutations that ameliorate this fitness cost can sometimes eventually stabilize a plasmid in a new host, but they typically do so by inactivating some of its novel accessory genes. In this study, we identified an additional evolutionary pathway that can prolong the maintenance of newly acquired genes encoded on a plasmid. We discovered that propagation of an RSF1010-based IncQ plasmid inEscherichia colioften generated ‘satellite plasmids’ with spontaneous deletions of accessory genes and genes required for plasmid replication. These smaller plasmid variants are nonautonomous genetic parasites. Their presence in a cell drives down the copy number of full-length plasmids, which reduces the burden from the accessory genes without eliminating them entirely. The evolution of satellite plasmids may be favored relative to other plasmid fates because they give a more immediate fitness advantage to a cell’s progeny and because the organization of IncQ plasmids makes them particularly prone to certain deletions during replication. Satellite plasmids also evolved inSnodgrassella alvicolonizing the honey bee gut, suggesting that this mechanism may broadly contribute to the importance of IncQ plasmids as agents of bacterial gene transfer in nature.Significance StatementPlasmids are multicopy DNA elements found in bacteria that replicate independently of a cell’s chromosome. The spread of plasmids carrying antibiotic-resistance genes to new bacterial pathogens is a challenge for treating life-threatening infections. Often plasmids or their accessory genes encoding unique functions are lost soon after transfer into a new cell because they impose a fitness burden. We report that a family of transmissible plasmids can rapidly evolve ‘satellite plasmids’ that replicate as genetic parasites of the original plasmid. Satellite plasmid formation reduces the burden from the newly acquired genes, which may enable them to survive intact for longer after transfer into a new cell and thereby contribute to the spread of antibiotic resistance and other traits within bacterial populations.

scholarly journals Identification of a Novel Conjugative Plasmid in Mycobacteria That Requires Both Type IV and Type VII Secretion

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Roy Ummels ◽  
Abdallah M. Abdallah ◽  
Vincent Kuiper ◽  
Anouar Aâjoud ◽  
Marion Sparrius ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Antibiotic Resistance Genes ◽  
Conjugative Plasmid ◽  
Content Type ◽  
Conjugative Plasmids ◽  
Type Vii Secretion ◽  
Type Iv ◽  
Slow Growing

ABSTRACTConjugative plasmids have been identified in a wide variety of different bacteria, ranging from proteobacteria to firmicutes, and conjugation is one of the most efficient routes for horizontal gene transfer. The most widespread mechanism of plasmid conjugation relies on different variants of the type IV secretion pathway. Here, we describe the identification of a novel type of conjugative plasmid that seems to be unique for mycobacteria. Interestingly, while this plasmid is efficiently exchanged between different species of slow-growing mycobacteria, includingMycobacterium tuberculosis, it could not be transferred to any of the fast-growing mycobacteria tested. Genetic analysis of the conjugative plasmid showed the presence of a locus containing homologues of three type IV secretion system components and a relaxase. In addition, a new type VII secretion locus was present. Using transposon insertion mutagenesis, we show that in fact both these secretion systems are essential for conjugation, indicating that this plasmid represents a new class of conjugative plasmids requiring two secretion machineries. This plasmid could form a useful new tool to exchange or introduce DNA in slow-growing mycobacteria.IMPORTANCEConjugative plasmids play an important role in horizontal gene transfer between different bacteria and, as such, in their adaptation and evolution. This effect is most obvious in the spread of antibiotic resistance genes. Thus far, conjugation of natural plasmids has been described only rarely for mycobacterial species. In fact, it is generally accepted thatM. tuberculosisdoes not show any recent sign of horizontal gene transfer. In this study, we describe the identification of a new widespread conjugative plasmid that can also be efficiently transferred toM. tuberculosis. This plasmid therefore poses both a threat and an opportunity. The threat is that, through the acquisition of antibiotic resistance markers, this plasmid could start a rapid spread of antibiotic resistance genes between pathogenic mycobacteria. The opportunity is that we could use this plasmid to generate new tools for the efficient introduction of foreign DNA in slow-growing mycobacteria.

scholarly journals Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
María Getino ◽  
David J. Sanabria-Ríos ◽  
Raúl Fernández-López ◽  
Javier Campos-Gómez ◽  
José M. Sánchez-López ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Aliphatic Chain ◽  
Bacterial Conjugation ◽  
Human Pathogens

ABSTRACT Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.

scholarly journals The Comprehensive Antibiotic Resistance Database

2013 ◽  
Vol 57 (7) ◽  
pp. 3348-3357 ◽  
Author(s):  
Andrew G. McArthur ◽  
Nicholas Waglechner ◽  
Fazmin Nizam ◽  
Austin Yan ◽  
Marisa A. Azad ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Sequence Data ◽  
Antibiotic Resistance Genes ◽  
Research Database ◽  
Free Living ◽  
Bacterial Populations ◽  
Bioinformatic Tools ◽  
Antibiotic Drug ◽  
Genetics And Genomics ◽  
Living Organisms

ABSTRACTThe field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD;http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.

scholarly journals Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance

2017 ◽  
Vol 114 (32) ◽  
pp. E6526-E6535 ◽  
Author(s):  
Radoslaw Pluta ◽  
D. Roeland Boer ◽  
Fabián Lorenzo-Díaz ◽  
Silvia Russi ◽  
Hansel Gómez ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Multidrug Resistant ◽  
High Energy ◽  
Structural Basis ◽  
Main Process ◽  
Bacterial Gene ◽  
Gram Positive Bacteria ◽  
Dna Nicking ◽  
Cell To Cell Transfer

Relaxases are metal-dependent nucleases that break and join DNA for the initiation and completion of conjugative bacterial gene transfer. Conjugation is the main process through which antibiotic resistance spreads among bacteria, with multidrug-resistant staphylococci and streptococci infections posing major threats to human health. The MOBV family of relaxases accounts for approximately 85% of all relaxases found in Staphylococcus aureus isolates. Here, we present six structures of the MOBV relaxase MobM from the promiscuous plasmid pMV158 in complex with several origin of transfer DNA fragments. A combined structural, biochemical, and computational approach reveals that MobM follows a previously uncharacterized histidine/metal-dependent DNA processing mechanism, which involves the formation of a covalent phosphoramidate histidine-DNA adduct for cell-to-cell transfer. We discuss how the chemical features of the high-energy phosphorus-nitrogen bond shape the dominant position of MOBV histidine relaxases among small promiscuous plasmids and their preference toward Gram-positive bacteria.

scholarly journals Non-antibiotic pharmaceuticals can enhance the spread of antibiotic resistance via conjugation

2019 ◽  
Author(s):  
Yue Wang ◽  
Ji Lu ◽  
Shuai Zhang ◽  
Jie Li ◽  
Likai Mao ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Cell Membrane ◽  
Membrane Permeability ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Protein Sequencing ◽  
Cell Membrane Permeability ◽  
Lipid Lowering ◽  
Potential Contribution

AbstractAntibiotic resistance is a global threat for public health. It is widely acknowledged that antibiotics at sub-inhibitory concentrations are important in disseminating antibiotic resistance via horizontal gene transfer. While there is high use of non-antibiotic human-targeted pharmaceuticals in our societies, the potential contribution of these on the spread of antibiotic resistance has been overlooked so far. Here, we report that commonly consumed non-antibiotic pharmaceuticals, including nonsteroidal anti-inflammatories (ibuprofen, naproxen, diclofenac), a lipid-lowering drug (gemfibrozil), and a β-blocker (propanolol), at clinically and environmentally relevant concentrations, significantly accelerated the conjugation of plasmid-borne antibiotic resistance genes. We looked at the response to these drugs by the bacteria involved in the gene transfer through various analyses that included monitoring reactive oxygen species (ROS) and cell membrane permeability by flow cytometry, cell arrangement, and whole-genome RNA and protein sequencing. We found the enhanced conjugation correlated well with increased production of ROS and cell membrane permeability. We also detected closer cell-to-cell contact and upregulated conjugal genes. Additionally, these non-antibiotic pharmaceuticals caused the bacteria to have responses similar to those detected when exposed to antibiotics, such as inducing the SOS response, and enhancing efflux pumps. The findings advance our understanding of the bacterial transfer of antibiotic resistance genes, and importantly emphasize concerns of non-antibiotic human-targeted pharmaceuticals for enhancing the spread of antibiotic resistance.

scholarly journals Compensatory evolution facilitates the acquisition of multiple plasmids in bacteria

2017 ◽  
Author(s):  
Alfonso Santos-Lopez ◽  
Cristina Bernabe-Balas ◽  
Alvaro San Millan ◽  
Rafael Ortega-Huedo ◽  
Andreas Hoefer ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Animal Health ◽  
Antibiotic Resistance Genes ◽  
Multicopy Plasmid ◽  
Bacterial Populations ◽  
Compensatory Evolution ◽  
Evolutionary Forces ◽  
Antimicrobial Resistance Genes ◽  
Biological Cost

AbstractThe coexistence of multicopy plasmids is a common phenomenon. However, the evolutionary forces promoting these genotypes are poorly understood. In this study, we have analyzed multiple ColE1 plasmids (pB1000, pB1005 and pB1006) coexisting within Haemophilus influenzae RdKW20 in all possible combinations. When transformed into the naïve host, each plasmid type presented a particular copy number and produced a specific resistance profile and biological cost, whether alone or coexisting with the other plasmids. Therefore, there was no fitness advantage associated with plasmid coexistence that could explain these common plasmid associations in nature. Using experimental evolution, we showed how H. influenzae Rd was able to completely compensate the fitness cost produced by any of these plasmids. Crucially, once the bacterium has compensated for a first plasmid, the acquisition of new multicopy plasmid(s) did not produced any extra biological cost. We argue therefore that compensatory adaptation pave the way for the acquisition of multiple coexisting ColE1 plasmids.ImportanceAntibiotic resistance is a major concern for human and animal health. Plasmids play a major role in the acquisition and dissemination of antimicrobial resistance genes. In this report we investigate, for the first time, how plasmids are capable to cohabit stably in populations. This coexistence of plasmids is driven by compensatory evolution alleviating the cost of a first plasmid, which potentiates the acquisition of further plasmids at no extra cost. This phenomenon explains the high prevalence of plasmids coexistance in wild type bacteria, which generates multiresistant clones and contributes to the maintenance and spread of antibiotic resistance genes within bacterial populations.

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