56 research outputs found
Bacterial protein interaction networks: connectivity is ruled by gene conservation, essentiality and function
Protein-protein interaction (PPI) networks are the backbone of all processes
in living cells. In this work we relate conservation, essentiality and
functional repertoire of a gene to the connectivity of the corresponding
protein in the PPI networks. Focusing on a set of 42 bacterial species with
reasonably separated evolutionary trajectories, we investigate three issues: i)
whether the distribution of connectivity values changes between PPI subnetworks
of essential and nonessential genes; ii) how gene conservation, measured both
by the evolutionary retention index (ERI) and by evolutionary pressures
(evaluated through the ratio and ENC plots) is related to the the
connectivity of the corresponding protein; iii) how PPI connectivities are
modulated by evolutionary and functional relationships, as represented by the
Clusters of Orthologous Proteins (COGs). We show that conservation,
essentiality and functional specialization of genes control in a quite
universal way the topology of the emerging bacterial PPI networks. Noteworthy,
a structural transition in the network is observed such that, for
connectivities , bacterial PPI networks are mostly populated by genes
that are conserved, essential and which, in most cases, belong to the COG
cluster J, related to ribosomal functions and to the processing of genetic
information
Codon Bias Patterns of 's Interacting Proteins
Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino
acid, are used differently across the variety of living organisms. The
biological meaning of this phenomenon, known as codon usage bias, is still
controversial. In order to shed light on this point, we propose a new codon
bias index, , that is based on the competition between cognate and
near-cognate tRNAs during translation, without being tuned to the usage bias of
highly expressed genes. We perform a genome-wide evaluation of codon bias for
, comparing with other widely used indices: , , and
. We show that and capture similar information by being
positively correlated with gene conservation, measured by ERI, and
essentiality, whereas, and appear to be less sensitive to
evolutionary-functional parameters. Notably, the rate of variation of and
with ERI allows to obtain sets of genes that consistently belong to
specific clusters of orthologous genes (COGs). We also investigate the
correlation of codon bias at the genomic level with the network features of
protein-protein interactions in . We find that the most densely
connected communities of the network share a similar level of codon bias (as
measured by and ). Conversely, a small difference in codon bias
between two genes is, statistically, a prerequisite for the corresponding
proteins to interact. Importantly, among all codon bias indices, turns
out to have the most coherent distribution over the communities of the
interactome, pointing to the significance of competition among cognate and
near-cognate tRNAs for explaining codon usage adaptation
Essentiality, conservation, evolutionary pressure and codon bias in bacterial genes
Essential genes constitute the core of genes which cannot be mutated too much nor lost along the adaptive evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bacterial species, each one characterised by its own codon usage bias. Confirming previous results on E- Coli, we show the existence of a universal exponential correlation between gene essentiality and conservation in bacteria. Moreover, we show that, within each bacterial genome, there are at least two groups of functionally distinct genes, characterised by different levels of conservation and codon bias: i) a core of essential genes, mainly related to cellular information processing; ii) a set of less conserved genes with prevalent functions related to metabolism. The genes in the first group are more retained among species, are subject to a relatively purifying conservative selection and display a more selected choice of synonymous codons.The core of essential genes is close to the minimal bacterial genome, which is in the focus of recent studies in synthetic biology, though we confirm that othologues of genes that are essential in one species are not necessarily essential in other species. We also list a set of highly shared genes, which could constitute a reservoir of targets for new anti-microbial drugs
Co-evolution between Codon Usage and Protein-Protein Interaction in Bacteria
We study the correlation between the codon usage bias of genetic sequences
and the network features of protein-protein interaction (PPI) in bacterial
species. We use PCA techniques in the space of codon bias indices to show that
genes with similar patterns of codon usage have a significantly higher
probability that their encoded proteins are functionally connected and
interacting. Importantly, this signal emerges when multiple aspects of codon
bias are taken into account at the same time. The present study extends our
previous observations on E.Coli over a wide set of 34 bacteria. These findings
could allow for future investigations on the possible effects of codon bias on
the topology of the PPI network, with the aim of improving existing
bioinformatics methods for predicting protein interactions
Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria
The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling
The Role of Interferon-Inducible Guanylate-Binding Proteins (GBPs) in Non-Canonical Inflammasome Activation
Caspase-4 Activation and Recruitment to Intracellular Gram-Negative Bacteria
The non-canonical inflammasome pathway functions as the primary cytosolic innate immune detection mechanism for Gram-negative bacterial lipopolysaccharide (LPS) in human and mouse cells and controls the proteolytic activation of the cell death executor gasdermin D (GSDMD). The main effectors of this pathways are the inflammatory proteases caspase-11 in mice and caspase-4/caspase-5 in humans. These caspases have been shown to bind LPS directly; however, the interaction between LPS and caspase-4/caspase-11 requires a set of interferon (IFN)-inducible GTPases, known as guanylate-binding proteins (GBPs). These GBPs assemble to form coatomers on cytosolic Gram-negative bacteria, which function as recruitment and activation platforms for caspase-11/caspase-4. Here we describe an assay to monitor caspase-4 activation in human cells by immunoblotting and its recruitment to intracellular bacteria using the model pathogen Burkholderia thailandensis
Codon usage bias and environmental adaptation in microbial organisms
In each genome, synonymous codons are used with different frequencies; this general phenomenon is known as codon usage bias. It has been previously recognised that codon usage bias could affect the cellular fitness and might be associated with the ecology of microbial organisms. In this exploratory study, we investigated the relationship between codon usage bias, lifestyles (thermophiles vs. mesophiles; pathogenic vs. non-pathogenic; halophilic vs. non-halophilic; aerobic vs. anaerobic and facultative) and habitats (aquatic, terrestrial, host-associated, specialised, multiple) of 615 microbial organisms (544 bacteria and 71 archaea). Principal component analysis revealed that species with given phenotypic traits and living in similar environmental conditions have similar codon preferences, as represented by the relative synonymous codon usage (RSCU) index, and similar spectra of tRNA availability, as gauged by the tRNA gene copy number (tGCN). Moreover, by measuring the average tRNA adaptation index (tAI) for each genome, an index that can be associated with translational efficiency, we observed that organisms able to live in multiple habitats, including facultative organisms, mesophiles and pathogenic bacteria, are characterised by a reduced translational efficiency, consistently with their need to adapt to different environments. Our results show that synonymous codon choices might be under strong translational selection, which modulates the choice of the codons to differently match tRNA availability, depending on the organism’s lifestyle needs. To our knowledge, this is the first large-scale study that examines the role of codon bias and translational efficiency in the adaptation of microbial organisms to the environment in which they live
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