Plasmids and Evolutionary Rescue by Drug Resistance

Tazzyman, Samuel J.; Bonhoeffer, Sebastian

doi:10.1111/evo.12423

Cited by 28 publications

(46 citation statements)

References 42 publications

(55 reference statements)

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“…Since the initial cell population is large, we describe the dynamics of wild-type homozygous cells deterministically (cf. Orr and Unckless, 2008; Tazzyman and Bonhoeffer, 2014; Uecker et al ., 2014; Uecker and Hermisson, 2016; Uecker, 2017). Hence: …”

Section: Analysis and Resultsmentioning

confidence: 99%

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Evolutionary rescue and drug resistance on multicopy plasmids

Santer

Uecker

2019

Preprint

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1Bacteria often carry "extra DNA" in form of plasmids in addition to their chro-2 mosome. Many plasmids have a copy number greater than one such that the genes 3 encoded on these plasmids are present in multiple copies per cell. This has evo-4 lutionary consequences by increasing the mutational target size, by prompting the 5 (transitory) co-occurrence of mutant and wild-type alleles within the same cell, and 6 by allowing for gene dosage effects. We develop and analyze a mathematical model for 7 bacterial adaptation to harsh environmental change if adaptation is driven by benefi-8 cial alleles on multicopy plasmids. Successful adaptation depends on the availability 9 of advantageous alleles and on their establishment probability. The establishment 10 process involves the segregation of mutant and wild-type plasmids to the two daugh-11 ter cells, allowing for the emergence of mutant-homozygous cells over the course of 12 several generations. To model this process, we use the theory of multi-type branch-13 ing processes, where a type is defined by the genetic composition of the cell. Both 14 factors -the number of adaptive alleles and their establishment probability -depend 15 on the plasmid copy number, and they often do so antagonistically. We find that 16 in the interplay of various effects, a lower or higher copy number may maximize the 17 probability of evolutionary rescue. The decisive factor is the dominance relationship 18 between mutant and wild-type plasmids and potential gene dosage effects. Results 19 from a simple model of antibiotic degradation indicate that the optimal plasmid copy 20 number may depend on the specific environment encountered by the population. 21 157 vidual establishes a permanent lineage of offspring. We provide an expression for p hom est in 158 Eq. (A.6). 159 Mathematical approach 160Whether the bacterial population successfully adapts or goes extinct depends on two factors: 161 the mutational supply and the establishment probability of the resistance mutation once 162

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Section: Analysis and Resultsmentioning

confidence: 99%

“…(see Orr and Unckless, 2008; Martin et al ., 2013; Tazzyman and Bonhoeffer, 2014; Uecker et al ., 2014; Uecker and Hermisson, 2016; Uecker, 2017; Anciaux et al ., 2018). The exponential function is the zeroth term of a Poisson distribution and gives the probability that no successful resistance mutation appears in time, i.e.…”

Section: Analysis and Resultsmentioning

confidence: 99%

Evolutionary rescue and drug resistance on multicopy plasmids

Santer

Uecker

2019

Preprint

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“…We account for this by concentrating on the appearance of rescue mutations, rather than simply phage-resistance mutations. [t] is the survival probability of a lineage of aP individuals descending from a single individual at time t (that is, the fixation probability for a new phage-resistant mutant on an a background) (Alexander and Bonhoeffer, 2012;Parzen, 1999 section 4.2, Tazzyman andBonhoeffer, 2014). The probability-generating function for the number of rescue mutations that have arisen at time t on an a background is then…”

Section: Modelmentioning

confidence: 99%

“…We use a birth-death approach (Parzen, 1999;Alexander andBonhoeffer, 2012 section 7.5, Tazzyman andBonhoeffer, 2014 …”

Section: Modelmentioning

confidence: 99%

“…To model the appearance of phage-resistance mutations, we used stochastic processes (Parzen, 1999) that have been used elsewhere to determine the probability of a population under strong selection being rescued from extinction by mutation (Alexander and Bonhoeffer, 2012;Martin et al, 2013;Tazzyman and Bonhoeffer, 2014). Our model and assumptions are as follows.…”

Section: Introductionmentioning

confidence: 99%

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Lytic phages obscure the cost of antibiotic resistance in Escherichia coli

Tazzyman

Hall

2014

The ISME Journal

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The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods.

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Livestock and Poultry: Other Colonists Who Changed the Food System of the Chesapeake Bay

Cuker

2020

Diet for a Sustainable Ecosystem

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The introduction of domesticated animals into the Chesapeake Bay regions’ food system had profound consequences for the health of the ecosystem and its people. Draft animals provided the labor to clear and cultivate the majority of the Chesapeake Bay Watershed by 1900. Pigs brought by English colonists became important sources of food for both the settlers and native peoples. Initially, introduced chickens played a persistent but minor role in the food system. This changed with the development of the chicken for meat (broiler) industry on the Bay’s Delmarva Peninsula in the 1920s. The broiler industry pioneered the use of concentrated animal feeding operations (CAFOs) and vertical integration of all aspects of production, a model now dominating the entire livestock enterprise. This propelled a 50% rise in per capita consumption of animal-based foods and attendant rise in human diseases, particularly coronary artery disease. Industrialization of chicken also increased its share of the animal products market sevenfold. The broiler industry pioneered the use of antibiotics as growth promoters, resulting in development of antibiotic-resistant pathogens. Poultry workers face various health problems, including increased rates of respiratory disease and certain cancers. The poultry industry is the major source of Salmonella poisoning. Broiler chickens suffer crowded and polluted conditions in CAFOs. These CAFOs dominate the landscape of the Delmarva, producing air and water pollution. Nitrogen as a waste product from the industry reaches the Bay and is a major source of eutrophication.

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Plasmids and Evolutionary Rescue by Drug Resistance

Cited by 28 publications

References 42 publications

Evolutionary rescue and drug resistance on multicopy plasmids

Evolutionary rescue and drug resistance on multicopy plasmids

Lytic phages obscure the cost of antibiotic resistance in Escherichia coli

Livestock and Poultry: Other Colonists Who Changed the Food System of the Chesapeake Bay

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