Type 3 secretion (T3S) is the only secretion system in Biology known to switch from a given set of secretion substrates to a completely different set of protein secretion substrates. We devised a simple genetic selection that revealed the presence of a protein lock, a gatekeeper, that holds the apparatus into "early" secretion mode. Upon completion of an intermediate flagellum assembly...
Pyoverdin is a water-soluble metal-chelator synthesized by members of the genus Pseudomonas and used for the acquisition of insoluble ferric iron. Although freely diffusible in aqueous environments, preferential dissemination of pyoverdin among adjacent cells, fine-tuning of intracellular siderophore concentrations, and fitness advantages to pyoverdin-producing versus nonproducing cells,...
Bacillus subtilis sporulation entails a dramatic transformation of the two cells required to assemble a dormant spore, with the larger mother cell engulfing the smaller forespore to produce the cell-within-a-cell structure that is a hallmark of endospore formation. Sporulation also entails metabolic differentiation, whereby key metabolic enzymes are depleted from the forespore but maintained...
Patients with cystic fibrosis (CF) face chronic antibiotic-resistant bacterial infections in their airways, lungs, other mucosal surfaces, and in some cases, bloodstream. Over the patients’ lifetime, these infections become exceedingly difficult to treat. Despite the profound benefits of corrector and modulator drugs that restore some function to the CFTR on quality of life and lifespan, ~10%...
Recent studies have demonstrated that the catabolism of germinant amino acids, such as alanine and valine, is crucial for preventing the premature germination of spores within their mother cells or shortly after their release into spent sporulation medium (1), (2). In Bacillus subtilis, mutants lacking alanine dehydrogenase (Ald) are unable to catabolize alanine, leading to its accumulation in...
As genetic analysis increasingly moves from one dimension (genotype-phenotype) to the second dimension (interactions between genotype-phenotype pairs) and even third dimension (additional mutations modifying the two-gene interactions), a better understanding of the complex effects is required to use this powerful tool intelligently. Of the four general types of genetic interactions (epistasis,...
Translation termination involves the recognition of stop codons by release factors (RFs). In bacteria, RF2 recognizes UGA and UAA stop codons and is encoded by the prfB gene. The translation of prfB is interrupted by an internal UGA stop codon on its coding sequence, resulting in negative autoregulation controlled by RF2 concentration. Complete translation can only occur when the internal stop...
Natural selection is the non-random differential reproduction of individuals in a population. Selection occurs upon a pool of already exiting variation. Thus, the outcome of selection depends on available phenotypic variation. Although mutations in the genome are random, generation of variant types is not random because of constraints and redundancy. Therefore, from all possible genotypes,...
Bacteria acquire new genes by horizontal gene transfer (HGT). Acquisition is typically mediated by mobile genetic elements (MGEs), however, beyond plasmids, bacteriophages and certain integrative conjugative elements (ICEs), the nature and diversity of MGEs is poorly understood. The bacterium Pseudomonas fluorescens SBW25 was propagated by serial transfer in the presence of filtrate obtained...
Successful recruitment, colonisation and stability of plant-associated microbial communities depends on the microbes’ ability to successfully interpret and appropriately respond to environmental signals. We have made considerable progress towards understanding soil community signalling and plant colonisation. However, the central role of mobile genetic elements (MGEs) – bacteriophages,...
Microbial proteome allocation has been introduced as a useful concept to rationalize metabolic switching and ribosome biology in fast microorganisms such as E. coli. When utilizing aerobically glucose at higher growth rates, E. coli initiates an overflow metabolism resulting in inefficient glucose utilization to accommodate the increased demand for ribosomes in the cellular proteome. Our work...
The ability to modulate translation capacity, which resides greatly on a number of ribosomes, provides robustness in fluctuating environments. Because translation is energetically the most expensive process in cells, cells must constantly adapt the rate of ribosome production to resource availability. This is primarily achieved by regulating ribosomal RNA (rRNA) synthesis, to which ribosomal...
Hybridization has shaped the evolutionary history of every kingdom of life. Hybridization inherently forces genomes that are not optimized to function together into the same cell. Remarkably, despite in some cases extreme sequence divergence upwards of 30%, cells can survive this challenge and even exploit it to rapidly evolve to new environments and create novelty. However, much of what we...
Horizontal gene transfer (HGT) is a fundamental process in bacterial evolution and is typically driven by mobile genetic elements, with conjugative plasmids one of the most significant sources of bacterial HGT. In addition to functional traits such as antibiotic resistance, plasmids also frequently encode homologs of bacterial regulators that can dramatically change the expression of...
Reproductive isolation is central to speciation, and hybrid sterility in Mus musculus subspecies provides a powerful model to study its genetic basis. A key player in this process is the HstX2 locus on the X chromosome, which in tandem with the only known hybrid sterility gene in vertebrates PRDM9, intriguingly regulates both meiotic recombination rate variation and hybrid male sterility, two...
Mutation rates vary within genomes, leading to biases in the genetic change that fuels evolution. Some regions have extreme rates of mutation and are referred to as mutational ‘hotspots’. Understanding the causes of hotspots are important if evolutionary biology is to become a more predictive science. We have taken advantage of a chance observation to show that genetic regulation can influence...
We will honor the memory of our dear friends and mentors, Pepe Casadesús and Rolf Menzel.
Talk: Roberto Balbontin, The legacy of Pepe Casadesús
Free-living bacteria often harbor multiple prophages integrated into their genomes, where these elements can cooperate to provide beneficial functions to their host. However, the peaceful coexistence among prophages ends if the host experiences genotoxic stress or other conditions that trigger the phage lytic cycle. Upon induction, prophages enter a competitive state. Phage competition comes...
MuC, along with core RNAP and σ70, is required for transcription of late genes of phage Mu. We observed that overexpression of MuC is lethal in E. coli and that host replication was over-initiating under these conditions. Suppressors of MuC lethality occurred in dnaA, diaA, and dnaX, genes involved in initiation of DNA replication. We hypothesized that lethality was likely due to increase in...
The life of phage Lambda (λ) has been extensively studied and has led to the current paradigmatic bifurcation of temperate phage life cycles along either lytic or lysogenic reproduction strategies. However, infection dynamics have long been studied using classical plating techniques that inevitably capture the more stable infection outcomes and tend to neglect the more transient phage-host...
Experimental evolution strategies to modulate bacteriophage life-history traits Manuela Reuter, Michael Sieber1, Octavio Reyes-Matte1, Christina Vasileiou1, Jordan Romeyer-Dherbey2, Christopher Böhmker1, Javier Lopez-Garrido1, Frederic Bertels1 1Max Planck Institute for Evolutionary Biology, Plön, Germany 2University of Cambridge, Cambridge, United Kingdom Bacteriophage’s life-history traits...
We resolved hundreds of bacteriophage genomes into distinct structural components through high-resolution assembly graph analysis of metagenomic datasets. We uncovered extensive genomic variation and quasispecies dynamics. Our analyses revealed a striking anti-correlation between genome plasticity and dominance, suggesting that phage populations balance genetic variability and selective...
The nucleoid-structuring protein H-NS silences segments of the enterobacterial genomes by binding to AT-rich nucleation sites and forming nucleoprotein filaments that block transcription over extended regions. H-NS:DNA filaments assemble on negatively supercoiled DNA and are stabilized by this DNA topology. In Salmonella, H-NS silences all major pathogenicity islands when the bacteria are...
Insertion sequence elements (ISEs) are small integrative genetic elements and abundant in bacterial genomes. ISE integration is a frequent cause of both pseudogenisation and promoter capture. Additionally, ISEs are recombination hotspots that stimulate spontaneous gene duplications amplifications and deletions. To study the hypothesised key role of ISEs in bacterial gene expression flexibility...
Interactions between microbes and vertebrate host is hypothesized to be regulated through the mucus, therefore, host associated microbiomes will have genes to utilize the carbohydrates that are produced in the host mucus. Therefore, we quantified the carbohydrate (monosaccharide) composition of the mucus from four sharks and rays (Elasmobranchii) and investigate the genomic machinery of the...
Chronic disease states are the most challenging to address, in part because they are not understood at a basic mechanistic level. Genetics has been a powerful tool to understanding the most intractable pathologies, but I will discuss why combining genetics with pharmacology is essential, using chronic pain as one specific example.
Fatty acids determine structural flexibility and thickness of membrane phospholipids, and changes in their composition necessarily affect cell function. While fatty acid composition would expectedly be strictly controlled, it is not: various cells incorporate environmental fatty acids directly into phospholipids, such that they ‘lose control’ of their membrane lipid composition. We are...
I will discuss the hypothesis that life may have evolved to evolve — a provocative idea given that it appears to require foresight on the part of natural selection. The controversy arises because evolvability is a property of lineages, not individuals, and thus implies that selection can operate at levels above single entities. To probe the mechanisms underlying evolvability, I will describe...
