Biology subjects

Dionisio, F.

Publications and source records attributed to Dionisio, F..

6 recordsLinked to original sources

bioRxiv2025

The Rare Plasmid Biosphere: A Hidden Reservoir of Genetic Diversity

Bacterial communities typically display highly uneven abundance patterns, with a few dominant taxa and many low-abundance ones contributing to extensive genetic diversity 1-4. Notably, this rare biosphere 5 includes species performing critical ecological functions, such as biogeochemical cycling and resisting invasions 6-9. While bacterial abundance patterns have been extensively studied, the distribution of plasmids-extrachromosomal, self-replicating genetic elements ubiquitous in prokaryotes-- remains poorly understood. Using a dataset of 52,909 plasmids from isolates of bacteria and archaea 10, we found that their 16,547 Plasmid Taxonomic Units (PTUs) 11,12 exhibit a distribution with a fat tail, whether in rank abundance or relative abundance distributions: a few highly prevalent PTUs and many rare. The relative abundance distributions are well described by a Poisson log-normal distribution, consistent with recent findings for species abundance distributions across several taxonomic groups 13. The host distribution also presents a heavy tail; however, we show that rare PTUs are not necessarily associated with rare bacterial species, nor are common PTUs exclusively found in common hosts. This indicates that PTUs distribution is not a direct consequence of hosts distribution. Per plasmid, the host range of rare PTUs is higher than that of common PTUs, at all taxa levels, from species to phyla. Yet, plasmids from common PTUs are more mobile, likely explaining their success. The large group of rare PTUs constitutes a much more diverse reservoir of genetic material than the group of common PTUs. Under appropriate selective pressures, some of these rare plasmids could spread not only by hitchhiking with their hosts but also through horizontal transfer. Therefore, this work opens new paths into plasmid research.

microbiology↗

bioRxiv2025

Conjugative Plasmids Rarely Confer Antibiotic Resistance or Virulence

Plasmids are autonomous DNA molecules that can replicate independently and transfer horizontally between bacterial cells. They play a key role in disseminating adaptive traits, such as antimicrobial resistance and virulence. Understanding plasmid mobility and its association with these traits is crucial to microbial ecology, public health and genomic surveillance. Several databases have been developed to catalogue plasmids assembled from bacterial isolates and metagenomic samples. However, differences in database construction and curation can introduce biases that affect subsequent analyses. In this study, we compare three distinct plasmid genome datasets -- the NCBI Reference Sequence Database (RefSeq), the Integrated Microbial Genomes & Microbiomes system (IMG/PR) from bacterial isolates (I) and microbiomes (M) -- to assess the influence of data origin on inferences about plasmid mobility types, antimicrobial resistance genes (ARGs), virulence genes (VGs) and host taxonomy. Our analysis reveals that plasmids assembled from metagenomes tend to be smaller than those assembled from isolates. RefSeq plasmids are enriched in conjugative plasmids (pCONJ) and display a higher frequency of ARGs and VGs. In contrast, regardless of whether they originate from isolates or metagenomes, IMG/PR plasmids are enriched in mobilizable plasmids (pMOB). Furthermore, ARGs are more frequently associated with highly mobile plasmids, particularly pCONJ. These findings highlight the importance of database selection in studies of plasmid epidemiology, functional potential and mobility. Standardised curation practices and cross-database comparisons are essential to ensure robust and reproducible insights into plasmid-mediated gene flow. ImportancePlasmids are DNA molecules that can replicate and transfer between bacteria, thereby helping to spread genes that enable bacteria to survive and adapt in different environments. This gene exchange plays a significant part in bacterial evolution. Researchers study these processes using plasmid databases, but the way these databases are constructed can influence the conclusions that are drawn. In this study, we found that key traits, such as those involved in antibiotic resistance and the ability to cause disease, are more often linked to plasmids with greater mobility, particularly in databases containing more clinical samples. However, our results demonstrate that the choice of dataset can significantly impact our understanding of the dissemination of critical genes among bacteria. These findings are valuable for tracking and controlling antibiotic resistance and disease, and highlight the need for carefully constructed, representative databases to support accurate research into how bacteria share genes.

genomics↗

bioRxiv2021

Follicular helper T cell signature of replicative exhaustion, apoptosis and senescence in common variable immunodeficiency

BackgroundCommon variable immunodeficiency (CVID) is the most frequent primary antibody deficiency. A significant number of CVID patients are affected by various manifestations of immune dysregulation such as autoimmunity. Follicular T cells cells are thought to support the development of CVID by providing inappropriate signals to B cells during the germinal center (GC) response. ObjectivesWe determined the possible role of follicular helper (Tfh) and follicular regulatory T (Tfr) cells in patients with CVID by phenotypic, molecular, and functional studies. MethodsWe analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh cells in the peripheral blood of 27 CVID patients (11 pediatric and 16 adult) displaying autoimmunity as additional phenotype and compared them to 106 (39 pediatric and 67 adult) age-matched healthy controls. We applied Whole Exome Sequencing (WES) and Sanger sequencing to identify mutations that could account for the development of CVID and associate with Tfh alterations. ResultsA group of CVID patients (n=9) showed super-physiological frequency of Tfh1 cells and a prominent expression of PD-1 and ICOS, as well as a Tfh RNA signature consistent with highly active, but exhausted and apoptotic cells. Plasmatic CXCL13 levels were elevated in these patients and positively correlated with Tfh1 cell frequency, PD-1 levels, and an elevated frequency of CD21loCD38lo autoreactive B cells. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were ideintified in four patients belonging to this group. Lymphocytes with highly shortened telomeres, and a Tfh signature enriched in genes involved in telomere elongation and response to DNA damage were seen. Histopathological analysis of the spleen in one patient showed reduced amount and size of the GC that, unexpectedly, contained an increased number of Tfh cells. ConclusionThese data point toward a novel pathogenetic mechanism in a group of patients with CVID, whereby alterations in DNA repair and telomere elongation might be involved in GC B cells, and acquisition of a Th1, highly activated but exhausted and apoptotic phenotype by Tfh cells.

immunology↗

bioRxiv2021

The power of dying slowly - persistence as unintentional dormancy

Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of -2. Studying persisters decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to -2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs. Author SummaryPersistence, a form of bacterial dormancy, was discovered in the early days of the antibiotic era. Thanks to dormancy, these cells often evade antibiotic therapy and the immune system. However, despite its clinical importance, this phenotypes nature is still under debate. Arguably, the prevailing view is that persistence is an evolved (selected for) bet-hedging mechanism to survive in the presence of cytotoxic agents such as antibiotics. In that case, the persister population should decay exponentially, although at a much slower pace than the non-persister population. A few authors recently advanced an alternative hypothesis: bacterial persistence results from many malfunctions and cell division errors. In this case, persistent populations should decay according to a power-law with exponent of -2, that is, according to 1/t2. Here we simulated the fate of susceptible bacterial cells in the presence of bactericidal antibiotics in the context of indirect resistance based on laboratory experiments performed earlier. By showing that the dynamics of persister cells is consistent with 1/t2, our results corroborate the hypothesis that the phenomenon of bacterial persistence is an accidental consequence of inadvertent cell problems and errors. If confirmed, this conclusion should impact the research strategies of anti-persistent drugs. O_QD"The following day, no one died. This fact, being absolutely contrary to lifes rules, provoked enormous and, in the circumstances, perfectly justifiable anxiety in peoples minds, for we have only to consider that in the entire forty volumes of universal history there is no mention, not even one exemplary case, of such a phenomenon ever having occurred..." Death with interruptions Jose Saramago (2005) Nobel Prize for Literature 1998 C_QD

microbiology↗

bioRxiv2020

Gene transmission and antibiotic usage are the key factors responsible for the positive correlation between antibiotic resistance gene diversity and virulence gene diversity in human metagenomes

1.This study aims to understand the cause of the recent observation that humans with a higher diversity of virulence genes in their metagenomes tend to be precisely those with higher diversity of antibiotic-resistance genes. We simulated the transferring of virulence and antibiotic-resistance genes in a community of interacting people where some take antibiotics. The diversities of the two genes types became positively correlated whenever the contagion probability between two people was higher than the probability of losing resistant genes. However, no such positive correlations arise if no one takes antibiotics. This finding holds even under changes of several simulations parameters, such as the relative or total diversity of virulence and resistance genes, the contagion probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the contagion between people and antibiotic usage is the leading cause of establishing the positive correlation mentioned above. Therefore, antibiotic use and something as prosaic as the contagion between people may facilitate the emergence of virulent and multi-resistant bacteria in peoples metagenomes with a high diversity of both gene types. These superbugs may then circulate in the community.

microbiology↗

bioRxiv2018

Correlation among antibiotic resistance and virulence traits in human gut microbiomes

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of non-pathogenic bacterial species are affected as well. Therefore, both pathogenic and non-pathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still co-occurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes issuing from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (ARd) and virulence factors (VFd) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut there are less ARd and VFd than in more diversified environments, and yet correlations between the ARd and VFd are stronger. They can vary from very high in Malawi, where antibiotic consumption is unattended, to non-existent in the uncontacted Amerindians. We conclude that there is co-occurrence of resistance and virulence determinants, suggesting a possible co-selective mechanism. For example, by selecting for resistant bacteria, we may be selecting for more virulent strains as a side effect of antimicrobial therapy.

genomics↗