Biology subjects

Brilli, M.

Publications and source records attributed to Brilli, M..

11 recordsLinked to original sources

bioRxiv2026

Modeling mosquito control strategies and their effect on pathogen transmission

The mosquito Aedes albopictus is a competent vector for the transmission of several arboviruses and is currently spreading across many continents. Since conventional control methods, like insecticides, often lead to environmental problems and the emergence of resistance, scientists developed alternative mosquito control strategies. One of the most used is the Sterile Insect Technique (SIT), which involves the mass release of males sterilized through irradiation. The Toxic Male Technique (TMT) is instead based on the release of genetically modified males expressing toxic proteins that kill females when they mate. Control strategies are often intended as methods to eradicate mosquito populations, yet a less ambitious and more cost-effective task is to reduce them such that the probability of transmission of viruses to humans becomes negligible. To compare the efficacy of these control strategies, we develop a mathematical model with two communicating compartments: a mosquito population and epidemiological model coupled with a human epidemiological model. As a proof-of-concept, we test the model using meteorological and entomological data for the Emilia-Romagna region. Our results indicate that the TMT strategy is more effective in lowering the probability of transmission and provides indication for the deployment of control strategies.

ecology↗

bioRxiv2026

The gut bacterial community of black soldier fly larvae is a reservoir of antibiotic resistance and virulence genes

1.Antimicrobial resistance (AMR) is a serious threat to global health. Agricultural practices that have contributed greatly to AMR spread urgently require innovation to address this issue, and more broadly challenges of sustainability and environmental concern. The larvae of black soldier fly (BSFL), Hermetia illucens, are considered a promising resource for advancing sustainable and circular agri-food systems given their ability to bioconvert organic waste streams into protein-and lipid-rich biomass suitable for feed applications and the use of the rearing residues (i.e., frass) as organic fertilisers. However, despite their emerging industrial applications, the risks of antibiotic resistance spread through their use remain underexplored. To elucidate this aspect, the profiles of antibiotic resistance genes (ARGs) and virulence factors (VFs), and their occurrence on plasmids were predicted from the midgut bacterial community of BSFL. Shotgun metagenomics revealed candidate resistance genes for 26 classes of antibiotics, and virulence via 9 mechanisms (with mobility and biofilm formation as major ones), with taxa belonging to the Pseudomonadota phylum as the dominant contributors. Highly relevant to public health was the identification of genes encoding resistance to carbapenem class antibiotics in bacterial genomes and mobile plasmids. Reconstruction of metagenomes enabled more precise taxonomic resolution and revealed taxa harbouring multiple resistance and virulence genes, including a Pseudomonas species with 42 VFs and 7 ARGs. Notably, for the first time antibiotic resistant bacterial species were isolated from the gut microbiota of BSFL, validating and complementing the results obtained in silico. Together, this work represents a comprehensive profile of the BSFL midgut bacterial resistome, while also providing relevant context on virulence and mobility. Importantly, it emphasises the urgent need to adopt strategies to mitigate potential risks arising from the development of emerging technologies related to the use of insect-mediated bioconversion and derived products.

genomics↗

bioRxiv2024

DO ORGANIC, CONVENTIONAL, AND INTENSIVE APPROACHES IN LIVESTOCK FARMING HAVE AN IMPACT ON THE CIRCULATION OF INFECTIOUS AGENTS? A SYSTEMATIC REVIEW, FOCUSED ON DAIRY CATTLE

A common thought is that extensive and organic breeding systems are associated with lower prevalence of infections in livestock animals, compared to intensive ones. In addition, organic systems limit the use of antimicrobial drugs, which may lead to lower emergence of antimicrobial resistances (AMR). To examine these issues, avoiding any a priori bias, we carried out a systematic literature search on dairy cattle breeding. Search was targeted to publications that compared different types of livestock farming (intensive, extensive, conventional, organic) in terms of the circulation of infectious diseases and AMR. A total of 101 papers were finally selected. These papers did not show any trend in the circulation of the infections in the four types of breeding systems. However, AMR was more prevalent on conventional dairy farms compared to organic ones. The prevalence of specific pathogens and types of resistances were frequently associated with specific risk factors that were not strictly related to the type of farming system. In conclusion, we did not find any evidence suggesting that extensive and organic dairy farming bears any advantage over the intensive and conventional ones, in terms of the circulation of infectious agents.

microbiology↗

bioRxiv2024

How to measure bacterial genome plasticity? A novel time-integrated index helps gather insights on pathogens

Genome plasticity can be defined as the capacity of a bacterial population to swiftly gain or lose genes. The time factor plays a fundamental role for the evolutionary success of microbes, particularly when considering pathogens and their tendency to gain antimicrobial resistance factors under the pressure of the extensive use of antibiotics. Multiple metrics have been proposed to provide insights into the gene content repertoire, yet they overlook the temporal component, which has a critical role in determining the adaptation and survival of a bacterial strain. In this study, we introduce a novel index that incorporates the time dimension to assess the rate at which bacteria exchange genes, thus fitting the definition of plasticity. Opposite to available indexes, our method also takes into account the possibility of contiguous genes being transferred together in one single event. We applied our novel index to measure plasticity in three widely studied bacterial species: Klebsiella pneumoniae, Staphylococcus aureus, and Escherichia coli. Our results highlight distinctive plasticity patterns in specific sequence types and clusters, suggesting a possible correlation between heightened genome plasticity and globally recognized high-risk clones. Our approach holds promise as an index for predicting the emergence of strains of potential clinical concern, possibly allowing for timely and more effective interventions. Impact statementHow quickly bacterial populations can acquire new functions is the key to their evolutionary success. This speed, called genome plasticity, is particularly relevant for human pathogens, especially when considering the acquisition of antimicrobial resistance. Today, the availability of large numbers of genomes from public databases makes it possible to develop a way to measure plasticity. However, none is currently available, besides indexes of gene content variability, which do not take into account the rate at which such gene content changes. In this work, we developed a plasticity index, called Flux Of Gene Segments (FOGS), and we tested it on large datasets of bacterial pathogen genomes. Interestingly, the subpopulations of the selected species that showed higher FOGS correspond to globally emerging high-risk clones. Therefore, we suggest that our index might be used not only to detect but also to predict emerging strains of human health concern. Data summaryThe authors confirm that all supporting data, code and protocols have been provided within the article or through supplementary data files.

genomics↗

bioRxiv2023

On the interactions of DNA replication and transcriptional regulation

DNA replication introduces a gradient of gene copy numbers, and in Bacteria it affects gene expression accordingly. In E. coli and other species, the slope of the gradient averaged over the population can be predicted on the basis of its relationship with growth rate. In this work we integrated this growth- and position-dependent gradient into a classical transcriptional regulation model, to highlight their interaction. The theoretical treatment of our model highlights that the sensitivity to transcription factor-mediated regulations acquires an additional dimension related to the position of a locus on the oriter axis and to division time. This reinforces the idea of replication as an additional layer in gene regulation. We highlight here that replication- and transcription factor-mediated regulations can in theory work in concert or counteract each other, and we discuss why this is important from an evolutionary point of view with respect to both steady state transcript abundance and its variance across conditions. Finally, we note that this treatment may improve the estimation of kinetic parameters for transcription factor activity using RNA-seq data, and the estimation of the dispersion factor in differential gene expression analysis when division time across conditions changes significantly.

systems biology↗

bioRxiv2023

Sinorhizobium meliloti FcrX coordinates cell cycle and division during free-living growth and symbiosis

Sinorhizobium meliloti is a soil bacterium that establishes a symbiosis within root nodules of legumes (Medicago sativa, for example) where it fixes atmospheric nitrogen into ammonia and obtains in return carbon sources and other nutrients. In this symbiosis, S. meliloti undergoes a drastic cellular change leading to a terminal differentiated form (called bacteroid) characterized by genome endoreduplication, increase of cell size and high membrane permeability. The bacterial cell cycle (mis)regulation is at the heart of this differentiation process. In free-living cells, the master regulator CtrA ensures the progression of cell cycle by activating cell division (controlled by the tubulin-like protein FtsZ) and simultaneously inhibiting supernumerary DNA replication, while on the other hand the downregulation of CtrA and FtsZ is essential for bacteroid differentiation during symbiosis, preventing endosymbiont division and permitting genome endoreduplication. Little is known in S. meliloti about regulators of CtrA and FtsZ, as well as the processes that control bacteroid development. Here, we combine cell biology, biochemistry and bacterial genetics approaches to understand the function(s) of FcrX, a new factor that controls both CtrA and FtsZ, in free-living growth and in symbiosis. Depletion of the essential gene fcrX led to abnormally high levels of FtsZ and CtrA and minicell formation. Using multiple complementary techniques, we showed that FcrX is able to interact physically with FtsZ and CtrA. Moreover, its transcription is controlled by CtrA itself and displays an oscillatory pattern in the cell cycle. We further showed that, despite a weak homology with FliJ-like proteins, only FcrX proteins from closely-related species are able to complement S. meliloti fcrX function. Finally, deregulation of FcrX showed abnormal symbiotic behaviors in plants suggesting a putative role of this factor during bacteroid differentiation. In conclusion, FcrX is the first known cell cycle regulator that acts directly on both, CtrA and FtsZ, thereby controlling cell cycle, division and symbiotic differentiation.

microbiology↗

bioRxiv2022

The selective force driving metabolic operon assembly

The evolution of operons has puzzled evolutionary biologists since their discovery and many theories exist to explain their emergence and spreading. The presence of several plausible hypotheses dealing with operon emergence/evolution/spreading is indicative of the absence of a universal causal factor for this evolutionary process. Here, we argue that the way in which DNA replication and cell division are coupled in microbial species introduces an additional selective force that may be responsible for the clustering of functionally related genes on chromosomes. We interpret this as a preliminary and necessary step in operon formation. Specifically, we start from the observation that during DNA replication differences in copy number of genes that are found at distant loci on the same chromosome arm exist. We provide theoretical considerations suggesting that, when genes of the same metabolic process are far away on the chromosome, this results in perturbations to metabolic homeostasis. By formalizing the effect of DNA replication on metabolic homeostasis based on Metabolic Control Analysis, we show that the above situation provides a selective force that can drive the formation of gene clusters and operons. Finally, we confirmed that, in present-day genomes, this force is significantly stronger in those species where the average number of active replication forks is larger and quantify the theoretical contribution of this feature on the distribution of extant gene clusters and operons.

systems biology↗

bioRxiv2020

Identification of variable sites in Sars-CoV-2 and their abundance profiles in time

The SARS-CoV-2 pandemic that we are currently experiencing is exerting a massive toll both in human lives and economic impact. One of the challenges we must face is to try to understand if and how different variants of the virus emerge and change their frequency in time. Such information can be extremely valuable as it may indicate shifts in aggressiveness, and it could provide useful information to trace the spread of the virus in the population. In this work we identified and traced over time 7 amino acid variants that are present with high frequency in Italy and Europe, but that were absent or present at very low frequencies during the first stages of the epidemic in China and the initial reports in Europe. The analysis of these variants helps defining 6 phylogenetic clades that are currently spreading throughout the world with changes in frequency that are sometimes very fast and dramatic. In the absence of conclusive data at the time of writing, we discuss whether the spread of the variants may be due to a prominent founder effect or if it indicates an adaptive advantage.

bioinformatics↗

bioRxiv2019

CcnA, a novel non-coding RNA regulating the bacterial cell cycle

Bacteria are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus, a cascade of essential master regulators supervises the correct and sequential activation of DNA replication, cell division and development of different cell types. Among them, the response regulator CtrA plays a crucial role coordinating all those functions. Here, for the first time we describe the role of a novel factor named CcnA, a cell cycle regulated ncRNA located at the origin of replication, presumably activated by CtrA and responsible for the accumulation of CtrA itself. In addition, CcnA may be also involved in the inhibition of translation of the S-phase regulator, GcrA, by interacting with its 5 untranslated region (5-UTR). Performing in vitro experiments and mutagenesis, we propose a mechanism of action of CcnA based on liberation (ctrA) or sequestration (gcrA) of their ribosome-binding site (RBS). Finally, its role may be conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a potentially conserved process modulating cell cycle in Caulobacterales and Rhizobiales.

microbiology↗

bioRxiv2018

Mutational likeliness and entropy help to identify driver mutations and their functional role in cancer

Alterations in cancer genomes originate from mutational processes taking place throughout oncogenesis and cancer progression. We show that likeliness and entropy are two properties of somatic mutations crucial in cancer evolution, as cancer-driver mutations stand out, with respect to both of these properties, as being distinct from the bulk of passenger mutations. Our analysis can identify novel cancer driver genes and differentiate between gain and loss of function mutations.

cancer biology↗

bioRxiv2017

The nucleoid as a scaffold for the assembly of bacterial signaling complexes

The FrzCD chemoreceptor from the gliding bacterium Myxococcus xanthus forms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas. This organization might be required for cooperative interactions between clustered receptors as observed in membrane-bound chemosensory arrays.\n\nAUTHOR SUMMARYIn this work, we show that the cytoplasmic chemoreceptor of the Frz chemosensory system, FrzCD, does not bind the cytoplasmic membrane like most MCPs but bind the bacterial nucleoid directly, thus forming distributed protein clusters also containing the Frz kinase. In vitro and in vivo experiments show that DNA-binding is not sequence-specific and is mediated by a basic aminoacid sequence of the FrzCD N-terminal domain. The deletion of this motif abolishes FrzCD DNA-binding and cooperativity in the response to signals. This work shows the importance of the nucleoid in the organization and functioning of cytoplasmic signaling systems in bacteria.

microbiology↗