Biology subjects

Sousa, J. M. d.

Publications and source records attributed to Sousa, J. M. d..

3 recordsLinked to original sources

bioRxiv2021

To catch a hijacker: abundance, evolution and genetic diversity of P4-like bacteriophage satellites

Bacteriophages (phages) are bacterial parasites that can themselves be parasitized by phage satellites. The molecular mechanisms used by satellites to hijack phages are sometimes understood in great detail, but the origins, abundance, distribution, and composition of these elements are poorly known. Here, we show that P4-like elements are present in more than 10% of the genomes of Enterobacterales, and in almost half of those of Escherichia coli, sometimes in multiple distinct copies. We identified over 1000 P4-like elements with very conserved genetic organization of the core genome and a few hotspots with highly variable genes. These elements are never found in plasmids and have very little homology to known phages, suggesting an independent evolutionary origin. Instead, they are scattered across chromosomes, possibly because their integrases are often exchanged with other elements. The rooted phylogenies of hijacking functions are correlated and suggest longstanding co-evolution. They also reveal broad host ranges in P4-like elements, since almost identical elements can be found in distinct bacterial genuses. Our results show that P4-like phage satellites constitute a very distinct, widespread and ancient family of mobile genetic elements. They pave the way for studying the molecular evolution of antagonistic interactions between phages and their satellites.

microbiology↗

bioRxiv2020

Genome diversification via genetic exchanges between temperate and virulent bacteriophages

Bacteriophages (phages) evolve rapidly by acquiring genes from other phages leading to mosaic genomes. Here, we identify numerous genetic transfers between distantly related phages and aim at understanding their frequency, consequences and the conditions favoring them. Gene flow tends to occur between phages that are enriched for recombinases, transposases and non-homologous end joining, suggesting that both homologous and illegitimate recombination contribute to gene flow. Phage family and host phyla are strong barriers to gene exchange, but phage lifestyle is not. We observe more exchanges between temperate phages even if they tend to have smaller genomes. These acquisitions often include transcription regulators and lysins. Yet, there is also extensive gene flow between temperate and virulent phages, or between the latter. These predominantly involve virulent phages with large genomes previously classed as low gene flux, and lead to the preferential transfer of genes encoding functions involved in cell energetics, nucleotide metabolism, DNA packaging and injection, and virion assembly. Such exchanges may explain the acquisition of genes in virulent phages, which tend to have the largest genomes. We used genetic transfers, which occur upon co-infection of a host, to compare phage host range. We found that virulent phages have broader host ranges and mediate genetic exchanges between narrow host range temperate phages infecting distant bacterial hosts, thus contributing to gene flow between virulent phages, as well as between temperate phages. This gene flow drastically expands the gene repertoires available for phage and bacterial evolution, including the transfer of functional innovations across taxa.

microbiology↗

bioRxiv2018

Modelling bacteria-phage interactions driving predation and horizontal gene transfer

Bacteriophages shape microbial communities by predating on them and by accelerating their adaptation through horizontal gene transfer. The former is the basis of phage therapy, whereas the latter drives the evolution of numerous bacterial pathogens. We present a novel computational approach (eVIVALDI - eco-eVolutionary mIcrobial indiViduAL-baseD sImulations) to study phage-bacteria ecological interactions that integrates a large number of processes, including population dynamics, environmental structure, genome evolution, and phage-mediated horizontal transfer. We validate and illustrate the relevance of the model by focusing on three specific questions: the ecological interactions between bacteria and virulent phage during phage and antibiotic therapy, the role of prophages as competitive weapons, and how autotransduction facilitates bacterial acquisition of antibiotic resistance genes upon lysis of antibiotic resistant competitors. Our model recapitulates experimental and theoretical observations and provides novel insights. In particular, we find that environmental structure has a strong effect on community dynamics and evolutionary outcomes in all three case studies. Strong environmental structure, relative to well-mixed environments and especially if antibiotics are heterogeneously distributed, enhances the rate of acquisition of resistance to both phages and antibiotics, and leads to more accurate predictions of the dynamics of lysogen invasion in the gastrointestinal tract. We predicted the co-existence of invaders and resident lysogens in autotransduction under a range of parameters, and validated this key prediction experimentally. By linking ecological and evolutionary dynamics, our modelling approach sheds light on the factors that influence the dynamics of phage-bacteria interactions. It can also be expanded to put forward novel hypotheses, facilitating the design of phage therapy treatments and the assessment of the role of phages in the spread of antibiotic resistance.\n\nAUTHOR SUMMARYIn the face of a growing threat of antibiotic resistant bacteria, bacteriophages have re-emerged as a potential alternative to clinical treatments of infections, as they are efficient bacterial predators. However, bacteriophages can also promote, through a mechanism called transduction, the dissemination of adaptive traits between bacteria, including antibiotic resistance genes. Importantly, these two types of interactions (predation and transduction) can co-occur, which creates difficulties in predicting their outcome. We have developed eVIVALDI (eco-eVolutionary mIcrobial indiViduAL-baseD sImulations), a computational model that allows the simulation of microbial communities with a focus on the mechanisms involved in phage-bacteria interactions, across time and in different types of environments. eVIVALDI can be used to understand the conditions where phages are more likely to be successfully used to eliminate bacteria or, in the other hand, the conditions where they increase the probability of dissemination of adaptive traits. Our research highlights the importance of considering the diverse ways that phage and bacteria interact, and the relevant ecological conditions where these interactions take place, to understand how bacteriophages shape microbial communities and how they can be used as a clinical tool.

microbiology↗