Biology subjects

Dottorini, T.

Publications and source records attributed to Dottorini, T..

4 recordsLinked to original sources

bioRxiv2023

Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China

Sharing among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 E. coli and S. enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance in Escherichia coli and susceptibility in Salmonella enterica. Many of these genes were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

genomics↗

bioRxiv2022

Predicting bioactivity of antibiotic metabolites by molecular docking and dynamics

Antibiotics enter the environment through waste streams, where they can exert selective pressure for antimicrobial resistance in bacteria. However, many antibiotics are excreted as partly metabolized forms, or can be subject to partial breakdown in wastewater treatment, soil, or through natural processes in the environment. If a metabolite is bioactive, even at sub-lethal levels, and also stable in the environment, then it could provide selection pressure for resistance. (5S)-penicilloic acid of piperacillin has previously been found complexed to the binding pocket of penicillin binding protein 3 (PBP3) of Pseudomonas aeruginosa. Here, we predicted the affinities of all potentially relevant antibiotic metabolites of ten different penicillins to that target protein, using molecular docking and molecular dynamics simulations. Docking predicts that, in addition to penicilloic acid, pseudopenicillin derivatives of these penicillins, as well as 6-aminopenicillanic acid (6APA), could also bind to this target. Molecular dynamics simulations further confirmed that (5R)-pseudopenicillin and 6APA bind the target protein, in addition to (5S)-penicilloic acid. Thus, it is possible that these metabolites are bioactive, and, if stable in the environment, could be contaminants selective for antibiotic resistance. This could have considerable significance for environmental surveillance for antibiotics as a means to reduce antimicrobial resistance, because targeted mass spectrometry could be required for relevant metabolites as well as the native antibiotics.

microbiology↗

bioRxiv2021

Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control.

DNA sequences that are exactly conserved over long evolutionary time scales have been observed in a variety of taxa. Such sequences are likely under strong functional constraint and they have been useful in the field of comparative genomics for identifying genome regions with regulatory function. A potential new application for these ultra-conserved elements has emerged in the development of gene drives to control mosquito populations. Many gene drives work by recognising and inserting at a specific target sequence in the genome, often imposing a reproductive load as a consequence. They can therefore select for target sequence variants that provide resistance to the drive. Focusing on highly conserved, highly constrained sequences lowers the probability that variant, gene drive-resistant alleles can be tolerated. Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were found across the alignment, with a maximum length of 164 bp. Length-corrected gene ontology analysis revealed that genes containing Anopheles ultra-conserved elements were over-represented in categories with structural or nucleotide binding functions. Known insect transcription factor binding sites were found in 48% of intergenic Anopheles ultra-conserved elements. When we looked at the genome sequences of 1142 wild-caught mosquitoes we found that 15% of the Anopheles ultra-conserved elements contained no polymorphisms. Our list of Anopheles ultra-conserved elements should provide a valuable starting point for the selection and testing of new targets for gene-drive modification in the mosquitoes that transmit malaria.

genomics↗

bioRxiv2017

Differential and defective expression of Koala Retrovirus reveal complexity of host and virus evolution

Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus free or to have only exogenous variants of KoRV with low rates of KoRV induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV induced disease such as lymphoma. This paper uses a combination of sequencing technologies, Illumina RNA sequencing of "southern" (south Australian) and "northern" (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of "southern" (South Australian and Victorian animals) to retrieve full length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication competent KoRV, are not in fact KoRV free but harbour defective, presumably endogenous, "RecKoRV" variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV induced disease.

microbiology↗