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Ghoul, M.

Publications and source records attributed to Ghoul, M..

6 recordsLinked to original sources

SOCfinder: a genomic tool for identifying cooperative genes in bacteria

Bacteria cooperate by working collaboratively to defend their colonies, share nutrients, and resist antibiotics. Nevertheless, our understanding of these remarkable behaviours primarily comes from studying a few well-characterized species. Consequently, there is a significant gap in our understanding of microbial cooperation, particularly in natural environments. To address this gap, we can use bioinformatic tools to identify cooperative traits and their underlying genes across diverse species. Existing tools address this challenge through two approaches. One approach is to identify genes that encode extracellular proteins, which can provide benefits to neighbouring cells. An alternative approach is to predict gene function using annotation tools. However, these tools have several limitations. Not all extracellular proteins are cooperative, and not all cooperative behaviours are controlled by extracellular proteins. Furthermore, existing functional annotation methods frequently miss known cooperative genes. Here, we introduce SOCfinder as a new tool to find cooperative genes in bacterial genomes. SOCfinder combines information from several methods, considering if a gene is likely to (1) code for an extracellular protein, (2) have a cooperative functional annotation, or (3) be part of the biosynthesis of a cooperative secondary metabolite. We use data on two extensively-studied species (P. aeruginosa & B. subtilis) to show that SOCfinder is better at finding known cooperative genes than existing tools. We also use theory from population genetics to identify a signature of kin selection in SOCfinder cooperative genes, which is lacking in genes identified by existing tools. SOCfinder opens up a number of exciting directions for future research, and is available to download from https://github.com/lauriebelch/SOCfinder. Data SummaryAll code and associated files are available at https://github.com/lauriebelch/SOCfinder. Impact StatementBacteria cooperate by secreting many molecules outside the cell, where they can provide benefits to other cells. While we know much about how bacteria cooperate in the lab, we know much less about bacterial cooperation in nature. Is cooperation equally important in all species? Are all cooperations equally vulnerable to cheating? To answer these questions, we need a way of identifying cooperative genes across a wide range of genomes. Here, we provide such a method - which we name SOCfinder. SOCfinder allows users to find cooperative genes in any bacterial genome. SOCfinder opens up a number of exciting directions for future research. It will allow detailed studies of non-model species, as well as broad comparative studies across species. These studies will allow cooperation in the wild to be studied in new ways.

evolutionary biology↗

Signatures of kin selection in a natural population of the bacteria Bacillus subtilis

Laboratory experiments have suggested that bacteria perform a range of cooperative behaviours, which are favoured because they are directed towards relatives (kin selection). However, there is a lack of evidence for cooperation and kin selection in natural bacterial populations. Molecular population genetics offers a promising method to study natural populations, because theory predicts that kin selection will lead to relaxed selection, which will result in increased polymorphism and divergence at cooperative genes. Examining a natural population of Bacillus subtilis, we found consistent evidence that putatively cooperative traits have higher polymorphism and greater divergence than putatively private traits expressed at the same rate. In addition, we were able to eliminate alternative explanations for these patterns, and found more deleterious mutations in genes controlling putatively cooperative traits. Overall, our results suggest cooperation favoured by kin selection, with an average relatedness of r=0.77 between interacting individuals.

evolutionary biology↗

Core and accessory effectors of type VI secretion systems contribute differently to the intraspecific diversity of Pseudomonas aeruginosa

Bacteria use type VI secretion systems (T6SSs) to deliver effector proteins into other cells or the extracellular space. Those effectors kill microbes1, manipulate eukaryotic cells2, and sequester nutrients3. Which T6SS-mediated functions are generalisable across bacteria of a species or are specific to particular strains is little known. Here, we use genomics to test for the intraspecific diversity of T6SS effectors in the opportunistic pathogen Pseudomonas aeruginosa. We found effectors that are omnipresent and conserved across strains acting as core effectors, while additional accessory effectors vary. In vitro and in vivo experiments demonstrate different roles of the two types of effectors in bacterial killing and virulence. Further, effectors compose various effector combinations. Within one local population of clinical isolates, we observed 36 combinations among 52 bacterial lineages. These findings show the distinct contribution of T6SS effectors to strain-level variation of a bacterial pathogen and might reveal conserved targets for novel antibiotics.

microbiology↗

An essential function for autocrine Hedgehog signaling in epithelial proliferation and differentiation in the trachea

The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (Hh) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a new, autocrine function of Hh signaling in airway epithelial cells. Epithelial cell depletion of the ligand Sonic hedgehog (SHH) or its effector Smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, Hh signaling inhibition also hampers cell proliferation and differentiation. Epithelial Hh function is mediated, at least in part, through transcriptional activation as Hh signaling inhibition leads to downregulation of cell-type specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of Hh signaling in epithelial cell proliferation and differentiation during airway development.

developmental biology↗

Long-term evolution of antibiotic persistence in P. aeruginosa lung infections

Pathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as persistence. While a variety of resistance mechanisms and underlying genetics are well characterised in vitro and in vivo, the evolution of persistence, and how it interacts with resistance in situ is less well understood. We assayed for persistence and resistance with three clinically relevant antibiotics: meropenem, ciprofloxacin and tobramycin, in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to forty years of evolution. We find evidence that persistence is under positive selection in the lung and that it can particularly act as an evolutionary stepping stone to resistance. However, this pattern is not universal and depends on the bacterial clone type and antibiotic used, indicating an important role for antibiotic mode of action.

evolutionary biology↗

Privatisation rescues function following loss of cooperation

A single cheating mutant can lead to the invasion and eventual eradication of cooperation from a population. Consequently, cheat invasion is often considered as \"game over\" in empirical and theoretical studies of cooperator-cheat dynamics, especially when cooperation is necessary for fulfilling an essential function. But is cheat invasion necessarily \"game over\" in nature? By following a population of bacteria through loss of cooperation and beyond, we observed that individuals evolved to replace cooperation with a selfish, or \"private\" behaviour. Specifically, we show that when cheating caused the loss of cooperative iron acquisition in a collection of Pseudomonas aeruginosa isolates from cystic fibrosis patients, a private uptake system that only benefits the focal individual was upregulated. This observation highlights the importance of social dynamics of natural populations and emphasizes the potential impact of past social interaction on the evolution of private traits.

evolutionary biology↗