scholarly journals The population and evolutionary dynamics of bacteriophage: Why be temperate revisited

2019 ◽  
Author(s):  
Waqas Chaudhry ◽  
Nicole Vega ◽  
Adithi Govindan ◽  
Rodrigo Garcia ◽  
Esther Lee ◽  
...  
Keyword(s):  
Natural Selection ◽  
Evolutionary Dynamics ◽  
Natural Populations ◽  
Lytic Phage ◽  
Temperate Bacteriophage ◽  
Serial Transfer ◽  
Virulent Phage ◽  
E Coli ◽  
Resistant Refractory

AbstractBacteriophages are deemed either lytic (virulent) or temperate, respectively depending on whether their genomes are transmitted solely horizontally, or both horizontally and vertically. To elucidate the ecological and evolutionary conditions under which natural selection will favor the evolution and maintenance of lytic or temperate modes of phage replication and transmission, we use a comprehensive mathematical model of the dynamics of temperate and virulent phage in populations of bacteria sensitive and resistant to these viruses. For our numerical analysis of the properties of this model, we use parameters estimated with the temperate bacteriophage Lambda, λ, it’s clear and virulent mutants, andE. colisensitive and resistant - refractory to these phages. Using batch and serial transfer population dynamic and reconstruction experiments, we test the hypotheses generated from this theoretical analysis. Based on the results of this jointly theoretical and experimental study, we postulate the conditions under which natural selection will favor the evolution and maintenance of lytic and temperate modes of phage replication and transmission. A compelling and novel prediction thisin silico,in vitro, andin plasticostudy makes is lysogenic bacteria from natural populations will be resistant-refractory to the phage for which they are lysogenic as well as lytic phage sharing the same receptors as these temperate viruses.

scholarly journals An experimental study of the population and evolutionary dynamics of Vibrio cholerae O1 and the bacteriophage JSF4

2010 ◽  
Vol 277 (1698) ◽  
pp. 3247-3254 ◽  
Author(s):  
Yan Wei ◽  
Paolo Ocampo ◽  
Bruce R. Levin
Keyword(s):  
Vibrio Cholerae ◽  
Evolutionary Dynamics ◽  
Natural Habitat ◽  
Natural Populations ◽  
Resistant Bacteria ◽  
Lytic Phage ◽  
Lytic Bacteriophage ◽  
El Tor ◽  
Short Time

Studies of Vibrio cholerae in the environment and infected patients suggest that the waning of cholera outbreaks is associated with rise in the density of lytic bacteriophage. In accordance with mathematical models, there are seemingly realistic conditions where phage predation could be responsible for declines in the incidence of cholera. Here, we present the results of experiments with the El Tor strain of V. cholerae (N16961) and a naturally occurring lytic phage (JSF4), exploring the validity of the main premise of this model: that phage predation limits the density of V. cholerae populations. At one level, the results of our experiments are inconsistent with this hypothesis. JSF4-resistant V. cholerae evolve within a short time following their confrontation with these viruses and their populations become limited by resources rather than phage predation. At a larger scale, however, the results of our experiments are not inconsistent with the hypothesis that bacteriophage modulate outbreaks of cholera. We postulate that the resistant bacteria that evolved play an insignificant role in the ecology or pathogenicity of V. cholerae . Relative to the phage-sensitive cells from whence they are derived, the evolved JSF4-resistant V. cholerae have fitness costs and other characters that are likely to impair their ability to compete with the sensitive cells in their natural habitat and may be avirulent in human hosts. The results of this in vitro study make predictions that can be tested in natural populations of V. cholerae and cholera-infected patients.

scholarly journals Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus

2020 ◽  
Author(s):  
Kaho H. Tisthammer ◽  
Weiyan Dong ◽  
Jeffrey B. Joy ◽  
Pleuni S. Pennings
Keyword(s):  
Drug Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Evolutionary Dynamics ◽  
Rna Virus ◽  
Natural Populations ◽  
Fitness Costs ◽  
Genome Wide

AbstractStudying in vivo fitness costs of mutations in viruses provides important insights into their evolutionary dynamics, which can help decipher how they adapt to host immune systems and develop drug resistance. However, studying fitness costs in natural populations is difficult, and is often conducted in vitro where evolutionary dynamics differ from in vivo. We aimed to understand in vivo fitness costs of mutations in Hepatitis C virus using next generation sequencing data. Hepatitis C virus is a positive-sense single-stranded RNA virus, and like many RNA viruses, has extremely high mutation and replication rates, making it ideal for studying mutational fitness costs. Using the ‘frequency-based approach’, we estimated genome-wide in vivo mutation frequencies at mutation-selection equilibrium, and inferred fitness costs (selection coefficients) at every genomic position using data from 195 patients. We applied a beta regression model to estimate the effects and the magnitudes of different factors on fitness costs. We generated a high-resolution genome-wide map of fitness costs in Hepatitis C virus for the first time. Our results revealed that costs of nonsynonymous mutations are three times higher than those of synonymous mutations, and mutations at nucleotides A/T have higher costs than those at C/G. Genome location had a modest effect, which is a clear contrast from previously reported in vitro findings, and highlights host immune selection. We inferred the strongest negative selection on the Core and NS5B proteins. We also found widespread natural prevalence of known drug resistance-associated variants in treatment naive patients, despite high fitness costs of these resistance sites. Our results indicate that in vivo evolutionary patterns and associated mutational costs are dynamic and can be virus specific, reinforcing the utility of constructing in vivo fitness cost maps of viral genomes.Author SummaryUnderstanding how viruses evolve within patients is important for combatting viral diseases, yet studying viruses within patients is difficult. Laboratory experiments are often used to understand the evolution of viruses, in place of assessing the evolution in natural populations (patients), but the dynamics will be different. In this study, we aimed to understand the within-patient evolution of Hepatitis C virus, which is an RNA virus that replicates and mutates extremely quickly, by taking advantage of high-throughput next generation sequencing. Here, we describe the evolutionary patterns of Hepatitis C virus from 195 patients: We analyzed mutation frequencies and estimated how costly each mutation was. We also assessed what factors made a mutation more costly, including the costs associated with drug resistance mutations. We were able to create a genome-wide fitness map of within-patient mutations in Hepatitis C virus which proves that, with technological advances, we can deepen our understanding of within-patient viral evolution, which can contribute to develop better treatments and vaccines.

scholarly journals Evaluation of a Cocktail of Three Bacteriophages for Biocontrol of Escherichia coli O157:H7

2004 ◽  
Vol 70 (6) ◽  
pp. 3417-3424 ◽  
Author(s):  
G. O'Flynn ◽  
R. P. Ross ◽  
G. F. Fitzgerald ◽  
A. Coffey
Keyword(s):  
Escherichia Coli ◽  
Biocontrol Agents ◽  
Lytic Phage ◽  
O157 Strain ◽  
E Coli ◽  
Phage Cocktail ◽  
Phage Sensitivity ◽  
Unit Reduction

ABSTRACT Escherichia coli O157:H7 is an endemic pathogen causing a variety of human diseases including mild diarrhea, hemorrhagic colitis, hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura. This study concerns the exploitation of bacteriophages as biocontrol agents to eliminate the pathogen E. coli O157:H7. Two distinct lytic phages (e11/2 and e4/1c) isolated against a human strain of E. coli O157:H7, a previously isolated lytic phage (pp01), and a cocktail of all three phages were evaluated for their ability to lyse the bacterium in vivo and in vitro. Phage e11/2, pp01, and the cocktail of all three virulent phages resulted in a 5-log-unit reduction of pathogen numbers in 1 h at 37�C. However, bacteriophage-insensitive mutants (BIMs) emerged following the challenge. All tested BIMs had a growth rate which approximated that of the parental O157 strain, although many of these BIMs had a smaller, more coccoid cellular morphology. The frequency of BIM formation (10−6 CFU) was similar for e11/2, pp01, and the phage cocktail, while BIMs insensitive to e4/1c occurred at the higher frequency (10−4 CFU). In addition, BIMs commonly reverted to phage sensitivity within 50 generations. In an initial meat trial experiment, the phage cocktail completely eliminated E. coli O157:H7 from the beef meat surface in seven of nine cases. Given that the frequency of BIM formation is low (10−6 CFU) for two of the phages, allied to the propensity of these mutants to revert to phage sensitivity, we expect that BIM formation should not hinder the use of these phages as biocontrol agents, particularly since low levels of the pathogen are typically encountered in the environment.

scholarly journals Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria

2020 ◽  
Vol 96 (10) ◽  
Author(s):  
Waqas Chaudhry ◽  
Esther Lee ◽  
Andrew Worthy ◽  
Zoe Weiss ◽  
Marcin Grabowicz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Genomic Analysis ◽  
High Rate ◽  
General Mechanism ◽  
Lytic Phage ◽  
Total Density ◽  
Serial Transfer ◽  
E Coli ◽  
General Answer ◽  
Mucoid Cells

ABSTRACT We present evidence that phage resistance resulting from overproduction of exopolysaccharides, mucoidy, provides a general answer to the longstanding question of how lytic viruses are maintained in populations dominated by bacteria upon which they cannot replicate. In serial transfer culture, populations of mucoid Escherichia coli MG1655 that are resistant to lytic phages with different receptors, and thereby requiring independent mutations for surface resistance, are capable of maintaining these phages with little effect on their total density. Based on the results of our analysis of a mathematical model, we postulate that the maintenance of phage in populations dominated by mucoid cells can be attributed primarily to high rates of transition from the resistant mucoid states to susceptible non-mucoid states. Our tests with both population dynamic and single cell experiments as well as genomic analysis are consistent with this hypothesis. We discuss reasons for the generalized resistance of these mucoid E. coli, and the genetic and molecular mechanisms responsible for the high rate of transition from mucoid to sensitive states responsible for the maintenance of lytic phage in mucoid populations of E. coli.

scholarly journals Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria

2019 ◽  
Author(s):  
Waqas Chaudhry ◽  
Esther Lee ◽  
Andrew Worthy ◽  
Zoe Weiss ◽  
Marcin Grabowicz ◽  
...  
Keyword(s):  
Surface Resistance ◽  
Molecular Mechanisms ◽  
High Rate ◽  
General Mechanism ◽  
Lytic Phage ◽  
Total Density ◽  
Serial Transfer ◽  
E Coli ◽  
General Answer ◽  
Mucoid Cells

AbstractWe present evidence that phage resistance resulting from overproduction of exopolysaccharides, mucoidy, provides a general answer to the longstanding question of how lytic viruses are maintained in populations dominated by bacteria upon which they cannot replicate. In serial transfer culture, populations of mucoid E. coli MG1655 that are resistant to lytic phages with different receptors, and thereby requiring independent mutations for surface resistance, are capable of maintaining these phages with little effect on their total density. Based on the results of our analysis of a mathematical model, we postulate that the maintenance of phage in populations dominated by mucoid cells can be attributed primarily to high rates of transition from the resistant mucoid states to susceptible non-mucoid states. Our tests with both population dynamic and single cell experiments as well as DNA sequence analysis are consistent with this hypothesis. We discuss reasons for the generalized resistance of these mucoid E. coli, and the genetic and molecular mechanisms responsible for the high rate of transition from mucoid to sensitive states responsible for the maintenance of lytic phage in mucoid populations of E. coli.

scholarly journals The effect of an intronic polymorphism on alcohol dehydrogenase expression in Drosophila melanogaster.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 379-385 ◽  
Author(s):  
C C Laurie ◽  
L F Stam
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Selection ◽  
Alcohol Dehydrogenase ◽  
Evolutionary Dynamics ◽  
In Vitro Mutagenesis ◽  
Allozyme Polymorphism ◽  
Selection Models ◽  
Intronic Polymorphism ◽  
Lines Of Evidence

Abstract Several lines of evidence indicate that natural selection controls the frequencies of an allozyme polymorphism at the alcohol dehydrogenase (Adh) locus in Drosophila melanogaster. However, because of associations among sequence polymorphisms in the Adh region, it is not clear whether selection acts directly (or solely) on the allozymic site. This problem has been approached by using in vitro mutagenesis to distinguish among the effects on Adh expression of individual polymorphisms. This study shows that a polymorphism within the first Adh intron (delta 1) has a significant effect on the level of ADH protein. Like the allozyme, delta 1 shows a geographic cline in frequency, indicating that it may also be a target of natural selection. These results suggest that multisite selection models may be required to understand the evolutionary dynamics of individual loci.

Local bacteriophage isolates showed anti-Escherichia coliO157:H7 potency in an experimental ligated rabbit ileal loop model

2011 ◽  
Vol 57 (5) ◽  
pp. 408-415 ◽  
Author(s):  
Muntasir Alam ◽  
Marufa Zerin Akhter ◽  
Mahmuda Yasmin ◽  
Chowdhury Rafiqul Ahsan ◽  
Jamalun Nessa
Keyword(s):  
Bacterial Growth ◽  
Lytic Phage ◽  
Loop Model ◽  
Ileal Loop ◽  
E Coli ◽  
Combined Application ◽  
Food Borne ◽  
In Vivo Testing

Escherichia coli O157:H7 is considered among the most important recently emerged food-borne bacteria causing severe hemorrhagic diarrhea. Antibiotic treatment is not recommended as a prospective curative agent against this pathogen. Therefore, potency assessment of the local lytic phage isolates infecting E. coli O157:H7 as an alternate remedy to antibiotics was the principal concern of this study. Phage isolates against E. coli O157:H7 were checked by polymerase chain reaction for the presence of the virulence genes stx1 and stx2, and the safe phages were further screened in vitro for their capacity as biocontrol agents. Two bacteriophage strains, namely PAH6 and P2BH2, that had expressed potential antibacterial activity (P < 0.05) in vitro were selected for in vivo testing in ligated rabbit ileal loop models. Both phage isolates were capable of decreasing fluid accumulation in rabbit ileal loops along with reducing bacterial growth (r = 0.992). Combined application of the phages was found most satisfactory, reducing seven log cycles of bacterial growth. Consistent results in both in vivo and in vitro experiments demonstrate the applicability of bacteriophages as a rapid response tool against E. coli O157:H7. To our knowledge, this is the first successful application of the rabbit ileal loop test for therapeutic evaluation of bacteriophages.

scholarly journals SELECTIVE NEUTRALITY OF 6PGD ALLOZYMES IN E. COLI AND THE EFFECTS OF GENETIC BACKGROUND

Genetics ◽  
1980 ◽  
Vol 96 (4) ◽  
pp. 801-817 ◽  
Author(s):  
Daniel Dykhuizen ◽  
Daniel L Hartl
Keyword(s):  
Natural Selection ◽  
Genetic Background ◽  
Natural Populations ◽  
Regulatory Elements ◽  
E Coli ◽  
Phosphogluconate Dehydrogenase ◽  
Selective Neutrality ◽  
Metabolic Route ◽  
Bacteriophage T5 ◽  
Direct Use

ABSTRACT We have used gluconate-limited chemostats to study selective differences between isogenic strains of Escherichia coli K12 into which four naturally occurring alleles coding for allozymes of 6-phosphogluconate dehydrogenase (6PGD) had been transferred. The limit of detectability of selection with our procedures is a selection coefficient of 0.5%. In the normal E. coli K12 genetic background, all alleles are selectively neutral or nearly neutral. The absence of detectable selection does, however, depend on genetic background and on such environmental factors as cell density. In a genetic background containing a mutation that cuts off the alternative metabolic route for 6-phosphogluconate, selection between allozymes can be detected, and the selection is in the direction expected from the measured apparent Km values of the allozymes. Even when the alternative metabolic route is not blocked by mutation, one of the 6PGD allozymes has a detrimental, but density-dependent, interaction with a mutation conferring resistance to bacteriophage T5. In all cases, the observed selection is due to the allozymes themselves (or to associated regulatory elements), as the selection disappears when the chemostats are limited by a different carbon source (ribose plus succinate). Nevertheless, the four alleles do seem to be selectively neutral or nearly neutral in the normal E. coli K12 genetic background. Moreover, the distribution of allele frequencies in natural populations of E. coli is in accord with the expectations of selective neutrality. I am inclined to suspect that we see, at least in some [cases], variations which are of no service to the species, and which consequently have not been seized on and rendered definite by natural selection…. Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed…. We may easily err in attributing importance to characters, and in believing that they have been developed through natural selection;… many structures are now of no direct use to their possessors, and may never have been of any use to their progenitors…. [On the other hand,] we are much too ignorant in regard to the whole economy of any organic being to say what slight modifications would be of importance or not.

Dwindling status of Epimedium Elatum (Morren & Decne) and its geographical distribution in Kashmir Himalaya, India

2018 ◽  
pp. 47-52
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Conservation Status ◽  
Natural Populations ◽  
Culture Techniques ◽  
Kashmir Himalayas ◽  
Near Future ◽  
First Time ◽  
Tissue Culture Techniques

Epimedium elatum (Morren & Decne) of family Berberidaceace is a rare perennial medicinal plant, endemic to high altitude forests of Northwestern Himalayas in India. Ethnobotanically, it has been used as an ingredient for treatment of bone-joint disorders, impotence and kidney disorders in Kashmir Himalayas. Phytochemically, it is rich in Epimedin ABC and Icariin; all of these have been demonstrated to possess remarkable biological activities like PDE-5 inhibition (treatment of erectile dysfunction), anticancer, antiosteoporosis antioxidant and antiviral properties. The present investigation reports its traditional usage, comprehensive distribution and conservation status from twenty ecogeographical regions in Kashmir Himalayas, India. The species was reported from Gurez valley for the first time. Numerous threats like excessive grazing, deforestration, habitat fragmentation, tourism encroachment, landslides and excessive exploitation have decreased its natural populations in most of the surveyed habitats. Consequently, its existence may become threatened in near future if timely conservation steps are not taken immediately by concerned stakeholders involved in medicinal plant research. Moreover, use of plant tissue culture techniques is recommended for development of its in vitro propagation protocols. Therefore, introduction of this medicinal plant in botanical gardens, protected sites and development of monitoring programmes are needed for its immediate conservation in Northwestern Himalayas, India.

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