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Avrani, S.

Publications and source records attributed to Avrani, S..

6 recordsLinked to original sources

A jumbo cyanophage encodes the most complete ribosomal protein set in the known virosphere

Viruses encode ribosomal proteins (RPs), but their genomes usually harbor a single RP-coding gene. Here, we reannotate the genome of the jumbo cyanophage PhiMa05 and show that it encodes six RPs, an RP acetyltransferase, and a ribosome biogenesis protein. Evolutionary analyses suggest that these viral RP-coding genes may have been horizontally transferred to certain members of the Vampirovibrionia, a non-photosynthetic basal lineage of Cyanobacteriota, via integration of the viral genome.

microbiology↗

Tradeoffs between phage resistance and nitrogen fixation drive the evolution of genes essential for cyanobacterial heterocyst functionality

Harmful blooms caused by diazotrophic (nitrogen-fixing) cyanobacteria are becoming increasingly frequent and negatively impact aquatic environments worldwide. Cyanophages (viruses infecting cyanobacteria) can potentially regulate cyanobacterial blooms, yet cyanobacteria can rapidly acquire mutations that provide protection against phage infection. Here, we provide novel insights into cyanophage:cyanobacteria interactions by characterizing the resistance to phages in two species of diazotrophic cyanobacteria: Nostoc sp. and Cylindrospermopsis raciborskii. Our results demonstrate that phage resistance is associated with a fitness tradeoff by which resistant cyanobacteria have reduced ability to fix nitrogen and/or to survive nitrogen starvation. Furthermore, we use whole genome sequence analysis of 58 Nostoc resistant strains to identify several mutations associated with phage resistance, including in cell surface-related genes, and regulatory genes involved in development and function of heterocysts (cells specialized in nitrogen fixation). Finally, we employ phylogenetic analyses to show that most of these resistance genes are accessory genes whose evolution is impacted by lateral gene transfer events. Together, these results further our understanding of the interplay between diazotrophic cyanobacteria and their phages, and suggest that a tradeoff between phage resistance and nitrogen fixation affects the evolution of cell surface-related genes and of genes involved in heterocyst differentiation and nitrogen fixation.

evolutionary biology↗

Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance

The evolution of antibiotic resistant bacteria threatens to become the leading cause of worldwide mortality. This crisis has renewed interest in the practice of phage therapy. Yet, bacterias capacity to evolve resistance is likely to debilitate this therapy as well. To combat the evolution of phage resistance and improve treatment outcomes, many have suggested leveraging phages ability to counter resistance by evolving phages on target hosts before using them in therapy (phage training). We found that during in vitro experiments, a phage trained for 28 days suppressed bacteria [~]1000-fold for 3-8 times longer than its untrained ancestor. This extension was due to a delay in the evolution of resistance. Several factors contributed to this prolonged suppression. Mutations that confer resistance to trained phages are [~]100x less common and, while the target bacterium can evolve complete resistance to the untrained phage in a single step, multiple mutations are required to evolve complete resistance to trained phages. Mutations that confer resistance to trained phages are more costly than mutations for untrained phage resistance. And when resistance does evolve, trained phages are better able to suppress these forms of resistance. One way the trained phage improved was through recombination with a gene in a defunct prophage in the host genome, which doubled phage fitness. This direct transfer of information encoded by the host but originating from a relict phage provides a previously unconsidered mode of training phage. Overall, we provide a case study for successful phage training and uncover mechanisms underlying its efficacy. Significance StatementThe evolution of antibiotic resistant bacteria threatens to claim over 10 million lives annually by 2050. This crisis has renewed interest in phage therapy, the use of bacterial viruses to treat infections. A major barrier to successful phage therapy is that bacteria readily evolve phage resistance. One idea proposed to combat resistance is "training" phages by using their natural capacity to evolve to counter resistance. Here, we show that training phages by coevolving them with their host for one month enhanced their capacity for suppressing bacterial growth and delayed the emergence of resistance. Enhanced suppression was caused by several mechanisms, suggesting that the coevolutionary training protocol produces a robust therapeutic that employs complementary modes of action.

evolutionary biology↗

Culture volume influences the dynamics of adaptation under long-term stationary phase

Escherichia coli and many other bacterial species, which are incapable of sporulation, can nevertheless survive within resource exhausted media by entering a state termed long-term stationary phase (LTSP). We have previously shown that E. coli populations adapt genetically under LTSP in an extremely convergent manner. Here we examine how the dynamics of LTSP genetic adaptation are influenced by varying a single parameter of the experiment - culture volume. We find that culture volume affects survival under LTSP, with viable counts decreasing as volumes increase. Across all volumes, mutations accumulate with time, and the majority of mutations accumulated demonstrate signals of being adaptive. However, positive selection appears to affect mutation accumulation more strongly at higher, compared to lower volumes. Finally, we find that several similar genes are likely involved in adaptation across volumes. However, the specific mutations within these genes that contribute to adaptation can vary in a consistent manner. Combined, our results demonstrate how varying a single parameter of an evolutionary experiment can substantially influence the dynamics of observed adaptation.

evolutionary biology↗

Dynamics of mutation accumulation and adaptation during three years of evolution under long-term stationary phase

Many bacterial species that cannot sporulate, such as the model bacterium Escherichia coli, can nevertheless survive for years under resource exhaustion, in a state termed long-term stationary phase (LTSP). Here we describe the dynamics of E. coli adaptation during the first three years spent under LTSP. We show that during this time E. coli continuously adapts genetically, through the accumulation of mutations. For non-mutator clones, the majority of mutations accumulated appear to be adaptive under LTSP, reflected in an extremely convergent pattern of mutation accumulation. Despite the rapid and convergent manner in which populations adapt under LTSP, they continue to harbor extensive genetic variation. The dynamics of evolution of mutation rates under LTSP are particularly interesting. The emergence of mutators, affects overall mutation accumulation rates as well as the mutational spectra and the ultimate spectrum of adaptive alleles acquired under LTSP. With time, mutators can evolve even higher mutation rates, through the acquisition of additional mutation-rate enhancing mutations. Different mutator and non-mutator clones within a single population and time point can display extreme variation in their mutation rates, resulting in differences in both the dynamics of adaptation and their associated deleterious burdens. Despite these differences, clones that vary greatly in their mutation rates tend to co-exist within their populations for many years, under LTSP.

evolutionary biology↗

Adaptations accumulated under prolonged resource exhaustion are highly transient

Many non-sproulating bacterial species can survive for years within exhausted growth media in a state termed long-term stationary phase (LTSP). We have been carrying out evolutionary experiments aimed at elucidating the dynamics of genetic adaptation under LTSP. We showed that Escherichia coli adapts to prolonged resource exhaustion through the highly convergent acquisition of mutations. In the most striking example of such convergent adaptation, we observed that across all independently evolving LTSP populations, over 90% of E. coli cells carry mutations to one of three specific sites of the RNA polymerase core enzyme (RNAPC). These LTSP adaptations reduce the ability of the cells carrying them to grow once fresh resources are again provided. Here, we examine how LTSP populations recover from costs associated with their adaptation, once resources are again provided to them. We demonstrate that due to the ability of LTSP populations to maintain high levels of standing genetic variation during adaptation, costly adaptations are very rapidly purged from the population once they are provided with fresh resources. We further demonstrate that recovery from costs acquired during adaptation under LTSP occurs much more rapidly than would be possible if LTSP adaptations had fixed during the time populations spent under resource exhaustion. Finally, we previously reported that under LTSP, some clones develop a mutator phenotype, greatly increasing their mutation accumulation rates. Here, we show that the mechanisms, by which populations recover from costs associated with fixed adaptations, may depend on mutator status.

evolutionary biology↗