scholarly journals Plasmid carriage can limit bacteria–phage coevolution

2015 ◽  
Vol 11 (8) ◽  
pp. 20150361 ◽  
Author(s):  
Ellie Harrison ◽  
Julie Truman ◽  
Rosanna Wright ◽  
Andrew J. Spiers ◽  
Steve Paterson ◽  
...  
Keyword(s):  
Conjugative Plasmid ◽  
Phage Resistance ◽  
Resistance Mutations ◽  
Accessory Gene ◽  
Bacterial Populations ◽  
High Frequencies ◽  
Qualitative Resistance ◽  
Selection For ◽  
Evolutionary Consequences ◽  
Plasmid Carriage

Coevolution with bacteriophages is a major selective force shaping bacterial populations and communities. A variety of both environmental and genetic factors has been shown to influence the mode and tempo of bacteria–phage coevolution. Here, we test the effects that carriage of a large conjugative plasmid, pQBR103, had on antagonistic coevolution between the bacterium Pseudomonas fluorescens and its phage, SBW25 ϕ 2. Plasmid carriage limited bacteria–phage coevolution; bacteria evolved lower phage-resistance and phages evolved lower infectivity in plasmid-carrying compared with plasmid-free populations. These differences were not explained by effects of plasmid carriage on the costs of phage resistance mutations. Surprisingly, in the presence of phages, plasmid carriage resulted in the evolution of high frequencies of mucoid bacterial colonies. Mucoidy can provide weak partial resistance against SBW25 ϕ 2, which may have limited selection for qualitative resistance mutations in our experiments. Taken together, our results suggest that plasmids can have evolutionary consequences for bacteria that go beyond the direct phenotypic effects of their accessory gene cargo.

scholarly journals Bacteriophages Limit the Existence Conditions for Conjugative Plasmids

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Ellie Harrison ◽  
A. Jamie Wood ◽  
Calvin Dytham ◽  
Jonathan W. Pitchford ◽  
Julie Truman ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Experimental Evolution ◽  
Phage Resistance ◽  
Bacterial Cells ◽  
Resistance Mutations ◽  
Weak Selection ◽  
Bacterial Populations ◽  
Conjugative Plasmids ◽  
Existence Conditions ◽  
Selection For

ABSTRACTBacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome.IMPORTANCEConjugative plasmids are infectious loops of DNA capable of transmitting DNA between bacterial cells and between species. Because plasmids often carry extra genes that allow bacteria to live in otherwise-inhospitable environments, their dynamics are central to understanding bacterial adaptive evolution. The plasmid-bacterium interaction has typically been studied in isolation, but in natural bacterial communities, bacteriophages, viruses that infect bacteria, are ubiquitous. Using experiments, mathematical models, and computer simulations we show that bacteriophages drive plasmid dynamics through their ecological and evolutionary effects on bacteria and ultimately limit the conditions allowing plasmid existence. These results advance our understanding of bacterial adaptation and show that bacteriophages could be used to select against plasmids carrying undesirable traits, such as antibiotic resistance.

scholarly journals High relatedness selects against hypermutability in bacterial metapopulations

2007 ◽  
Vol 274 (1615) ◽  
pp. 1341-1347 ◽  
Author(s):  
Freya Harrison ◽  
Angus Buckling
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Kin Selection ◽  
Model Organism ◽  
Wild Type ◽  
Dense Population ◽  
High Frequencies ◽  
Pathogen Virulence ◽  
Potential Disadvantage ◽  
Selection For ◽  
Evolutionary Consequences

Mutation rate and cooperation have important ecological and evolutionary consequences and, moreover, can affect pathogen virulence. While hypermutability accelerates adaptation to novel environments, hypermutable lineages (‘mutators’) are selected against in well-adapted populations. Using the model organism Pseudomonas aeruginosa , we previously demonstrated a further potential disadvantage to hypermutability, namely, that it can accelerate the breakdown of cooperation. We now investigate how this property of mutators can affect their persistence in metapopulations. Mutator and wild-type bacteria were competed for 250 generations in globally competing metapopulations, imposing conditions of high or low intra-deme relatedness. High relatedness favours cooperating groups, so we predicted that mutators should achieve lower equilibrium frequencies under high relatedness than under low relatedness. This was observed in our study. Consistent with our hypothesis, there was a positive correlation between mean mutator and cheat frequencies. We conclude that when dense population growth requires cooperation, and when cooperation is favoured (high relatedness), demes containing high frequencies of mutators are likely to be selected against because they also contain high frequencies of non-cooperating cheats. We have also identified conditions where mutator lineages are likely to dominate metapopulations; namely, when low relatedness reduces kin selection for cooperation. These results may help to explain clinical distributions of mutator bacteria.

scholarly journals Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria

2017 ◽  
Author(s):  
Antoine Frénoy ◽  
Sebastian Bonhoeffer
Keyword(s):  
Population Dynamics ◽  
Mutation Rate ◽  
Death Rate ◽  
Mutation Rates ◽  
Resistance Mutations ◽  
Bacterial Populations ◽  
Plasmid Segregation ◽  
Genome Wide ◽  
Response To Stress ◽  
Induced Mutagenesis

AbstractThe stress-induced mutagenesis paradigm postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to withstand the stress. This has implications for antibiotic treatment: exposure to sub-inhibitory doses of antibiotics has been reported to increase bacterial mutation rates, and thus probably the rate at which resistance mutations appear and lead to treatment failure.Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet sub-inhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus giving more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress.We developed a system using plasmid segregation to measure death and growth rates simultaneously in bacterial populations. We use it to replicate classical experiments reporting antibiotic-induced mutagenesis. We found that a substantial death rate occurs at the tested sub-inhibitory concentrations, and taking this death into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover even when antibiotics increase mutation rate, sub-inhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics.Beside showing that population dynamic is a crucial but neglected parameter affecting evolvability, we provide better experimental and computational tools to study evolvability under stress, leading to a re-assessment of the magnitude and significance of the stress-induced mutagenesis paradigm.

scholarly journals Broadscale phage therapy is unlikely to select for widespread evolution of bacterial resistance to virus infection

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Frederick M Cohan ◽  
Matthew Zandi ◽  
Paul E Turner
Keyword(s):  
Bacterial Resistance ◽  
Phage Therapy ◽  
Patient Treatment ◽  
Resistant Bacteria ◽  
Bacterial Populations ◽  
Recent Success ◽  
Adaptive Value ◽  
Global Spread ◽  
Classic Approach ◽  
Selection For

Abstract Multi-drug resistant bacterial pathogens are alarmingly on the rise, signaling that the golden age of antibiotics may be over. Phage therapy is a classic approach that often employs strictly lytic bacteriophages (bacteria-specific viruses that kill cells) to combat infections. Recent success in using phages in patient treatment stimulates greater interest in phage therapy among Western physicians. But there is concern that widespread use of phage therapy would eventually lead to global spread of phage-resistant bacteria and widespread failure of the approach. Here, we argue that various mechanisms of horizontal genetic transfer (HGT) have largely contributed to broad acquisition of antibiotic resistance in bacterial populations and species, whereas similar evolution of broad resistance to therapeutic phages is unlikely. The tendency for phages to infect only particular bacterial genotypes limits their broad use in therapy, in turn reducing the likelihood that bacteria could acquire beneficial resistance genes from distant relatives via HGT. We additionally consider whether HGT of clustered regularly interspaced short palindromic repeats (CRISPR) immunity would thwart generalized use of phages in therapy, and argue that phage-specific CRISPR spacer regions from one taxon are unlikely to provide adaptive value if horizontally-transferred to other taxa. For these reasons, we conclude that broadscale phage therapy efforts are unlikely to produce widespread selection for evolution of bacterial resistance.

scholarly journals Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations

2012 ◽  
Vol 205 (12) ◽  
pp. 1821-1829 ◽  
Author(s):  
A. N. Kunz ◽  
A. A. Begum ◽  
H. Wu ◽  
J. A. D'Ambrozio ◽  
J. M. Robinson ◽  
...  
Keyword(s):  
Fluoroquinolone Resistance ◽  
Resistance Mutations ◽  
In Vivo Selection ◽  
Compensatory Mutations ◽  
Selection For

scholarly journals Macroevolutionary consequences of sexual conflict

2018 ◽  
Vol 14 (6) ◽  
pp. 20180186
Author(s):  
Jo S. Hermansen ◽  
Jostein Starrfelt ◽  
Kjetil L. Voje ◽  
Nils C. Stenseth
Keyword(s):  
Sexual Selection ◽  
Genetic Architecture ◽  
Time Frame ◽  
Sexual Conflicts ◽  
Males And Females ◽  
Selection For ◽  
Evolutionary Consequences ◽  
Future Work ◽  
Shared Genetic

Intralocus sexual conflicts arise whenever the fitness optima for a trait expressed in both males and females differ between the sexes and shared genetic architecture constrains the sexes from evolving independently towards their respective optima. Such sexual conflicts are commonplace in nature, yet their long-term evolutionary consequences remain unexplored. Using a Bayesian phylogenetic comparative framework, we studied the macroevolutionary dynamics of intersexual trait integration in stalk-eyed flies (Diopsidae) spanning a time frame of more than 25 Myr. We report that increased intensity of sexual selection on male eyestalks is associated with reduced intersexual eyestalk integration, as well as sex-specific rates of eyestalk evolution. Despite this, lineages where males have been under strong sexual selection for millions of years still exhibit high levels of intersexual trait integration. This low level of decoupling between the sexes may indicate that exaggerated female eyestalks are in fact adaptive—or alternatively, that there are strong constraints on reducing trait integration between the sexes. Future work should seek to clarify the relative roles of constraints and selection in contributing to the varying levels of intersexual trait integration in stalk-eyed flies, and in this way clarify whether sexual conflicts can act as constraints on adaptive evolution even on macroevolutionary time scales.

scholarly journals The effect of phage genetic diversity on bacterial resistance evolution

2020 ◽  
Vol 14 (3) ◽  
pp. 828-836 ◽  
Author(s):  
Jenny M. Broniewski ◽  
Sean Meaden ◽  
Steve Paterson ◽  
Angus Buckling ◽  
Edze R. Westra
Keyword(s):  
Bacterial Resistance ◽  
Minor Role ◽  
Bacterial Populations ◽  
Immune Systems ◽  
Resistance Evolution ◽  
Adaptive Immune ◽  
Rapid Extinction ◽  
Selection For ◽  
Adaptive Immune Systems ◽  
Over Time

AbstractCRISPR-Cas adaptive immune systems are found in bacteria and archaea and provide defence against phage by inserting phage-derived sequences into CRISPR loci on the host genome to provide sequence specific immunological memory against re-infection. Under laboratory conditions the bacterium Pseudomonas aeruginosa readily evolves the high levels of CRISPR-based immunity against clonal populations of its phage DMS3vir, which in turn causes rapid extinction of the phage. However, in nature phage populations are likely to be more genetically diverse, which could theoretically impact the frequency at which CRISPR-based immunity evolves which in turn can alter phage persistence over time. Here we experimentally test these ideas and found that a smaller proportion of infected bacterial populations evolved CRISPR-based immunity against more genetically diverse phage populations, with the majority of the population evolving a sm preventing phage adsorption and providing generalised defence against a broader range of phage genotypes. However, those cells that do evolve CRISPR-based immunity in response to infection with more genetically diverse phage acquire greater numbers of CRISPR memory sequences in order to resist a wider range of phage genotypes. Despite differences in bacterial resistance evolution, the rates of phage extinction were similar in the context of clonal and diverse phage infections suggesting selection for CRISPR-based immunity or sm-based resistance plays a relatively minor role in the ecological dynamics in this study. Collectively, these data help to understand the drivers of CRISPR-based immunity and their consequences for bacteria-phage coexistence, and, more broadly, when generalised defences will be favoured over more specific defences.

scholarly journals Horizontal Spread of Rhodococcus equi Macrolide Resistance Plasmid pRErm46 across Environmental Actinobacteria

2020 ◽  
Vol 86 (9) ◽  
Author(s):  
Sonsiray Álvarez-Narváez ◽  
Steeve Giguère ◽  
Londa J. Berghaus ◽  
Cody Dailey ◽  
José A. Vázquez-Boland
Keyword(s):  
Bacterial Species ◽  
Low Frequency ◽  
Rhodococcus Equi ◽  
Macrolide Resistance ◽  
Conjugative Plasmid ◽  
Bacterial Populations ◽  
Prolonged Incubation ◽  
Content Type ◽  
Host Restriction

ABSTRACT Conjugation is one of the main mechanisms involved in the spread and maintenance of antibiotic resistance in bacterial populations. We recently showed that the emerging macrolide resistance in the soilborne equine and zoonotic pathogen Rhodococcus equi is conferred by the erm(46) gene carried on the 87-kb conjugative plasmid pRErm46. Here, we investigated the conjugal transferability of pRErm46 to 14 representative bacteria likely encountered by R. equi in the environmental habitat. In vitro mating experiments demonstrated conjugation to different members of the genus Rhodococcus as well as to Nocardia and Arthrobacter spp. at frequencies ranging from ∼10−2 to 10−6. pRErm46 transfer was also observed in mating experiments in soil and horse manure, albeit at a low frequency and after prolonged incubation at 22 to 30°C (environmental temperatures), not 37°C. All transconjugants were able to transfer pRErm46 back to R. equi. Conjugation could not be detected with Mycobacterium or Corynebacterium spp. or several members of the more distant phylum Firmicutes such as Enterococcus, Streptococcus, or Staphylococcus. Thus, the pRErm46 host range appears to span several actinobacterial orders with certain host restriction within the Corynebacteriales. All bacterial species that acquired pRErm46 expressed increased macrolide resistance with no significant deleterious impact on fitness, except in the case of Rhodococcus rhodnii. Our results indicate that actinobacterial members of the environmental microbiota can both acquire and transmit the R. equi pRErm46 plasmid and thus potentially contribute to the maintenance and spread of erm(46)-mediated macrolide resistance in equine farms. IMPORTANCE This study demonstrates the efficient horizontal transfer of the Rhodococcus equi conjugative plasmid pRErm46, recently identified as the cause of the emerging macrolide resistance among equine isolates of this pathogen, to and from different environmental Actinobacteria, including a variety of rhodococci as well as Nocardia and Arthrobacter spp. The reported data support the notion that environmental microbiotas may act as reservoirs for the endemic maintenance of antimicrobial resistance in an antibiotic pressurized farm habitat.

scholarly journals The evolution of bacterial mutation rates under simultaneous selection by interspecific and social parasitism

2013 ◽  
Vol 280 (1773) ◽  
pp. 20131913 ◽  
Author(s):  
Siobhán O'Brien ◽  
Antonio M. M. Rodrigues ◽  
Angus Buckling
Keyword(s):  
Mutation Rate ◽  
Social Parasitism ◽  
Mutation Rates ◽  
Bacterial Populations ◽  
Simultaneous Selection ◽  
Bacterial Mutation ◽  
Selection For ◽  
Intraspecific Parasitism ◽  
Theory And Experiments ◽  
Mutation Rate Evolution

Many bacterial populations harbour substantial numbers of hypermutable bacteria, in spite of hypermutation being associated with deleterious mutations. One reason for the persistence of hypermutators is the provision of novel mutations, enabling rapid adaptation to continually changing environments, for example coevolving virulent parasites. However, hypermutation also increases the rate at which intraspecific parasites (social cheats) are generated. Interspecific and intraspecific parasitism are therefore likely to impose conflicting selection pressure on mutation rate. Here, we combine theory and experiments to investigate how simultaneous selection from inter- and intraspecific parasitism affects the evolution of bacterial mutation rates in the plant-colonizing bacterium Pseudomonas fluorescens. Both our theoretical and experimental results suggest that phage presence increases and selection for public goods cooperation (the production of iron-scavenging siderophores) decreases selection for mutator bacteria. Moreover, phages imposed a much greater growth cost than social cheating, and when both selection pressures were imposed simultaneously, selection for cooperation did not affect mutation rate evolution. Given the ubiquity of infectious phages in the natural environment and clinical infections, our results suggest that phages are likely to be more important than social interactions in determining mutation rate evolution.

scholarly journals Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance

2002 ◽  
Vol 15 (4) ◽  
pp. 647-679 ◽  
Author(s):  
José L. Martínez ◽  
Fernando Baquero
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Virulence ◽  
Human Populations ◽  
Genetic Determinants ◽  
Bacterial Populations ◽  
Antibiotic Resistant ◽  
Regulatory Circuits ◽  
The Future ◽  
History Of ◽  
Evolutionary Consequences

SUMMARY Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.

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