Biology subjects

Garzon, A.

Publications and source records attributed to Garzon, A..

5 recordsLinked to original sources

bioRxiv2026

Evolutionary expansion of the bacterial ompW gene family enables functional diversification during host adaptation

The outer membrane protein W (OmpW) family comprises minor porins essential for environmental adaptation and host interactions in Gram-negative bacteria. However, ompW is conventionally treated as a ubiquitous single-copy gene, masking its true evolutionary complexity. Through comprehensive phylogenetic analysis across thousands of reference genomes, we reveal that ompW is present in nearly half of Gram-negative lineages, exhibiting a patchy distribution governed by a birth-and-death model of evolution with recurrent duplications and horizontal transfer. Notably, copy number expansions concentrate in lineages associated with eukaryotic hosts, linking paralog accumulation to niche adaptation. Experimental validation in Acinetobacter baumannii reveals four distinct loci that maintain high structural conservation despite sequence divergence, yet undergo profound functional specialization spanning from baseline physiological maintenance to modulating host colonization and persistence in vitro and in vivo. These findings dismantle the single-copy paradigm, demonstrating that widespread gene family expansion and paralog diversification drive the phenotypic plasticity required for bacteria to colonize hostile host environments.

microbiology↗

bioRxiv2024

The defensome of Acinetobacter baumannii reveals two genome groups according to their innate defense systems and phage profile

Phages are guilty of killing daily almost half of bacterial cells, while bacteria have developed defense mechanisms that number in the dozens. Individual defense systems are gained and lost by genomes of the same species, depending on their fitness advantage. Thus, some genomes have a certain combination of defense systems, while other genomes act as a reservoir for the rest of the systems, thus constituting the so-called pan-immune system of the species. Here we have analyzed thousands of genomes of the bacterium Acinetobacter baumannii, an opportunistic pathogen of humans of great clinical concern, and we have found 81 different defense systems heterogeneously distributed. By analyzing how these systems combine, we have found that more than half of the genomes lack the universal DNA-methylating restriction-modification systems (R-M) and harbor an alternative innate SspBCDE system that performs a DNA phosphorothioate modification. In addition, the adaptive CRISPR-Cas systems could act synergistically to the R-M systems, based on their frequency of co-appearance. The presence of one or the other innate system could modulate the evolution of the genomes of this species, causing them to present a different profile of phages integrated into the bacterial genome. We have also observed that the presence of many defense systems is associated with the presence of a higher number of prophages, which could be due to the fact that the prophage carries the system, or that the bacterium would not need these systems in environments where the phage is absent.

microbiology↗

bioRxiv2023

A biological warfare between two bacterial viruses in a particular genomic region using a CRISPR-Cas system as a weapon

CRISPR-Cas systems are acquired immunity systems of bacteria and archaea that prevent infection by phages and other mobile genetic elements. It is currently known that this defense system has also been co-opted by viruses. These viruses could use CRISPR-Cas systems to compete against other rival viruses. We have discovered a virus in the bacterium Acinetobacter baumannii that incorporates a CRISPR-Cas system into an integration hotspot of the host genome. Once integrated, this could prevent the infection of the most frequent viruses in this bacterial species, especially one that competes with the CRISPR-Cas system itself for the same integration site. This latter virus is prevalent in strains of the species belonging to the so-called Global Clone 2, which causes the most frequent outbreaks worldwide. Knowledge of this new viral warfare using CRISPR-Cas systems, known to limit the entry of antibiotic resistance genes into bacteria, could be useful in the fight against the infections they cause. But it would also shed light on the way in which these defense systems expand in bacteria.

bioinformatics↗

bioRxiv2022

An outstanding bacterial membranome requires CRISPR-Cas systems to avoid the intervention of phages

Antimicrobial resistance is widely recognized as a serious global public health problem. To combat this threat, a thorough understanding of bacterial genomes is necessary. The current wide availability of bacterial genomes provides us with an in-depth understanding of the great variability of dispensable genes and their relationship with antimicrobials. Some of these accessory genes are those involved in CRISPR-Cas systems, which are acquired immunity systems that are present in part of bacterial genomes. They prevent viral infections through small DNA fragments called spacers. But the vast majority of these spacers have not yet been associated with the virus they recognize, and this has been named CRISPR dark matter. By analyzing the spacers of tens of thousands of genomes from six bacterial species highly resistant to antibiotics, we have been able to reduce the CRISPR dark matter from 80-90% to as low as 15% in some of the species. In addition, we have observed that, when a genome presents CRISPR-Cas systems, this is accompanied by particular collections of membrane proteins. Our results suggest that when a bacterium presents membrane proteins that make it compete better in its environment, and these proteins are in turn receptors for specific phages, it would be forced to acquire CRISPR-Cas immunity systems to avoid infection by these phages.

bioinformatics↗

bioRxiv2020

Serial co-expression analysis of host factors from SARS-CoV viruses highly converges with former high-throughput screenings and proposes key regulators and co-option of cellular pathways

The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data now allows the design of secondary analyses that take advantage of this information to create new knowledge through specific computational approaches. One of these feasible analyses is the evaluation of the expression level for a gene through a series of different conditions or cell types. Based on this idea, we have developed ASACO, Automatic and Serial Analysis of CO-expression, which performs expression profiles for a given gene along hundreds of normalized and heterogeneous transcriptomics experiments and discover other genes that show either a similar or an inverse behavior. It might help to discover co-regulated genes, and even common transcriptional regulators in any biological model, including human diseases or microbial infections. The present SARS-CoV-2 pandemic is an opportunity to test this novel approach due to the wealth of data that is being generated, which could be used for validating results. In addition, new cell mechanisms identified could become new therapeutic targets. Thus, we have identified 35 host factors in the literature putatively involved in the infectious cycle of SARS-CoV and/or SARS-CoV-2 and searched for genes tightly co-expressed with them. We have found around 1900 co-expressed genes whose assigned functions are strongly related to viral cycles. Moreover, this set of genes heavily overlap with those identified by former laboratory high-throughput screenings (with p-value near 0). Some of these genes aim to cellular structures such as the stress granules, which could be essential for the virus replication and thereby could constitute potential targets in the current fight against the virus. Additionally, our results reveal a series of common transcription regulators, involved in immune and inflammatory responses, that might be key virus targets to induce the coordinated expression of SARS-CoV-2 host factors. All of this proves that ASACO can discover gene co-regulation networks with potential for proposing new genes, pathways and regulators participating in particular biological systems. HighlightsO_LIASACO identifies regulatory associations of genes using public transcriptomics data. C_LIO_LIASACO highlights new cell functions likely involved in the infection of coronavirus. C_LIO_LIComparison with high-throughput screenings validates candidates proposed by ASACO. C_LIO_LIGenes co-expressed with hosts genes used by SARS-CoV-2 are related to stress granules. C_LI

bioinformatics↗