Biology subjects

Pleska, M.

Publications and source records attributed to Pleska, M..

4 recordsLinked to original sources

bioRxiv2023

Bacterial toxin-antitoxin system MazEF as a native defense mechanism against RNA phages in Escherichia coli

Bacteria have evolved a wide range of defense strategies to protect themselves against bacterial viruses (phages). However, the known mechanisms almost exclusively target phages with DNA genomes. While several bacterial toxin-antitoxin systems have been considered to cleave single-stranded bacterial RNA in response to stressful conditions, their role in protecting bacteria against phages with single-stranded RNA genomes has not been studied. Here we investigate the role of a representative toxin-antitoxin system, MazEF, in protecting Escherichia coli against two RNA phages - MS2 and Q{beta}. Our population-level experiments revealed that a mazEF deletion strain is more susceptible to RNA phage infection than the wild-type. At the single-cell level, deletion of the mazEF locus significantly shortened the time to lysis of individual bacteria challenged with RNA phage. At the genomic level, we found that the adenine-cytosine-adenine sequence, directly recognized and cleaved by the MazF toxin, is systematically underrepresented in the genomes of RNA phages that are known to infect E. coli, indicating selection for decreased probability of cleavage. These results suggest that in addition to other physiological roles, RNA-degrading toxin-antitoxin modules can function as a primitive immune system against RNA phages.

microbiology↗

bioRxiv2020

Population dynamics of decision making in temperate bacteriophages

Due to their ability to choose between lysis and lysogeny, temperate bacteriophages represent a classic model system to study the molecular basis of decision making. The coinfection of individual bacteria by multiple, genetically identical phages is known to alter the infection outcome and favor lysogeny over lytic development. However, it is not clear what role the ability of individual phages to sense and respond to coinfections plays in the phage-host infection dynamics at the population level. To address this question, we developed a full-stochastic model to capture the interaction dynamics between billions of bacteria and phages with single-cell and -phage resolution. While, at the level of individual bacteria, the probability of coinfections depends mainly on the phage concentration at the time of infection, the average number of coinfections at the population level is primarily determined by the relative growth rate of phage. Because the maximum attainable phage growth rate is constrained by basic life history parameters, the average number of coinfections has an upper bound of around two. However, for a broad range of conditions, the average number of coinfections stays well below this value. Consequently, we find that coinfections provide only very limited information to individual phages about the state of the infection at the population level. Nevertheless, this information can still provide a strong competitive advantage for phages that base fate decisions on the number of coinfections.

evolutionary biology↗

bioRxiv2018

Why Put-Up with Immunity when there is Resistance: An Excursion into the Population and Evolutionary Dynamics of Restriction-Modification and CRISPR-Cas

Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction-modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions, under which selection mediated by lytic phage will favor such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the length of the co-evolutionary arms race between the bacteria acquiring spacers and the phage generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered.\n\nSummaryThe two most widely used tools for manipulating and editing DNA restriction and Cas9 endonucleases both originate from studies of mechanisms that provide bacteria with immunity to infections with lytic bacteriophage (phage): restriction modification and CRISPR-Cas. Using mathematical and computer simulations, we explore the a priori conditions under which selection mediated by lytic phage will favor the evolution and maintenance of restriction-modification and CRISPR-Cas immunity in bacteria that, by mutation, can generate envelope resistance to these phage. The results of our analysis make predictions and raise testable-hypotheses about the genetic and ecological conditions under which these immune systems, rather than envelope resistance, will evolve and be maintained as the dominant mechanism of protecting bacteria from succumbing to infections with these viruses.

evolutionary biology↗

bioRxiv2018

Molecular noise shapes bacteria-phage ecologies

Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their steady state population size, with the first strategy favoring simple and the second strategy favoring complex bacterial innate immunity.

biophysics↗