Biology subjects

Benler, S.

Publications and source records attributed to Benler, S..

5 recordsLinked to original sources

bioRxiv2021

Cargo genes of Tn7-like transposons comprise an enormous diversity of defense systems, mobile genetic elements and antibiotic resistance genes

Transposition is a major mechanism of horizontal gene mobility in prokaryotes. However, exploration of the genes mobilized by transposons (cargo) is hampered by the difficulty in delineating integrated transposons from their surrounding genetic context. Here, we present a computational approach that allowed us to identify the boundaries of 6,549 Tn7-like transposons at base pair resolution. We found that 96% of these transposons carry at least one cargo gene. Delineation of distinct communities in a gene-sharing network demonstrates how transposons function as a conduit of genes between phylogenetically distant hosts. Comparative analysis of the cargo genes reveals significant enrichment of mobile genetic elements (MGEs) nested within Tn7-like transposons, such as insertion sequences and toxin-antitoxin modules, genes involved in recombination and anti-MGE defense, and in antibiotic resistance. More unexpectedly, cargo also includes genes encoding central carbon metabolism enzymes. Twenty- two Tn7-like transposons carry both an anti-MGE defense system and antibiotic resistance genes, illustrating how bacteria can overcome these combined pressures upon acquisition of a single transposon. This work substantially expands the distribution of Tn7-like transposons, defines their evolutionary relationships and provides a large-scale functional classification of prokaryotic genes mobilized by transposition. SignificanceTransposons are major vehicles of horizontal gene transfer that, in addition to genes directly involved in transposition, carry cargo genes. However, characterization of these genes is hampered by the difficulty of identification of transposon boundaries. We developed a computational approach for detecting transposon ends and applied it to perform a comprehensive census of the cargo genes of Tn7-like transposons, a large class of bacterial mobile genetic elements (MGE), many of which employ a unique, CRISPR-mediated mechanism of site- specific transposition. The cargo genes encompass a striking diversity of MGE, defense and antibiotic resistance systems. Unexpectedly, we also identified cargo genes encoding metabolic enzymes. Thus, Tn7-like transposons mobilize a vast repertoire of genes that can have multiple effects on the host bacteria.

genomics↗

bioRxiv2021

Alternating lysis and lysogeny is a winning strategy in bacteriophages due to Parrondo's Paradox

Temperate bacteriophages lyse or lysogenize the host cells depending on various parameters of infection, a key one being the host population density. However, the effect of different propensities of phages for lysis and lysogeny on phage fitness is an open problem. We explore a nonlinear dynamic evolution model of competition between two phages, one of which is disadvantaged in both the lytic and lysogenic phases. We show that the disadvantaged phage can win the competition by alternating between the lytic and lysogenic phases, each of which individually is a "loser". This counter-intuitive result recapitulates Parrondos paradox in game theory, whereby individually losing strategies can combine to produce a winning outcome. The results suggest that evolution of phages optimizes the ratio between the lysis and lysogeny propensities rather than the phage reproduction rate in any individual phase. These findings are expected to broadly apply to the evolution of host-parasite interactions.

bioinformatics↗

bioRxiv2020

Thousands of previously unknown phages discovered in whole-community human gut metagenomes

BackgroundDouble-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut phageome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut. ResultsA search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3,738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, "Flandersviridae" and "Quimbyviridae", include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides and Prevotella. The third proposed family, "Gratiaviridae", consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some "Quimbyviridae" phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several "Flandersviridae" phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The "Gratiaviridae" phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species. ConclusionsAnalysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.

microbiology↗

bioRxiv2020

Unique genomic features of crAss-like phages, the dominant component of the human gut virome

CrAssphage is the most abundant virus identified in the human gut virome and the founding member of a large group of bacteriophages that infect bacteria of the phylum Bacteroidetes and have been discovered by metagenomics of both animal-associated and environmental habitats. By analysis of circular contigs from human gut microbiomes, we identified nearly 600 genomes of crAss-like phages. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, which can be expected to become a new order of viruses, and of 5 distinct branches, likely, families within that order. Two of these putative families have not been identified previously. The phages in one of these groups have large genomes (145-192 kilobases) and contain an unprecedented high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable readthrough of UGA or UAG stop-codons, mostly, in late phage genes, which could represent a distinct anti-defense strategy. Another putative anti-defense mechanism that might target an unknown defense system in Bacteroidetes inhibiting phage DNA replication involves multiple switches of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals several unusual features of genome architecture and expression as well as phage biology that were not apparent from the previous crAssphage analyses.

microbiology↗

bioRxiv2019

A Distinct Contractile Injection System Found in a Majority of Adult Human Microbiomes

An imbalance of normal bacterial groups such as Bacteroidales within the human gut is correlated with diseases like obesity. A current grand challenge in the microbiome field is to identify factors produced by normal microbiome bacteria that cause these observed health and disease correlations. While identifying factors like a bacterial injection system could provide a missing explanation for why Bacteroidales correlates with host health, no such factor has been identified to date. The lack of knowledge about these factors is a significant barrier to improving therapies like fecal transplants that promote a healthy microbiome. Here we show that a previously ill-defined Contractile Injection System is carried in the gut microbiome of 99% of individuals from the United States and Europe. This type of Contractile Injection System, we name here Bacteroidales Injection System (BIS), is related to the contractile tails of bacteriophage (viruses of bacteria) and have been described to mediate interactions between bacteria and diverse eukaryotes like amoeba, insects and tubeworms. Our findings that BIS are ubiquitous within adult human microbiomes suggest that they shape host health by mediating interactions between Bacteroidales bacteria and the human host or its microbiome.

microbiology↗