ORCID Profile
0000-0002-4395-060X
Current Organisations
University of Maryland at College Park
,
Flinders University
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Publisher: Microbiology Society
Date: 04-09-2023
Publisher: Center for Open Science
Date: 26-09-2022
Abstract: The gut virome is an incredibly complex part of the gut ecosystem. Gut viruses play a role in many disease 9 states, but it is not yet known to what extent the gut virome impacts everyday human health. New 10 experimental and bioinformatic approaches are required to address this knowledge gap. Gut virome 11 colonisation begins at birth, becoming temporally stable over a 30-month period. The stable virome is highly 12 specific to each in idual and is modulated by varying factors such as age, gender, diet, and disease state. 13 The gut virome is primarily composed of bacteriophages—predominantly crAssphage, and other 14 Caudovirales. The stability of the virome’s regular constituents is disrupted by disease. Transferring the 15 faecal microbiome and its viruses from a healthy in idual can restore the functionality of the gut, and 16 alleviates the symptoms of some chronic illnesses. Investigation of the virome is a relatively novel field with 17 new genetic sequences being published at an increasing rate. Many of these present with a large percentage 18 of unknown proteins, this ‘viral dark matter’ is one of the major questions facing virologists and 19 bioinformaticians. Bioinformatics tools can be used to explore both new and existing publicly available viral 20 sequence datasets to quantify and classify viral species, but not all these tools are created equal, with some 21 being more precise, effective, and efficient than others. Here, we review the literature surrounding the gut 22 virome, how it is established, how it impacts human health, the methods used to investigate it, and the viral 23 dark matter veiling the understanding of the gut virome.
Publisher: Oxford University Press (OUP)
Date: 21-09-2023
Publisher: Cold Spring Harbor Laboratory
Date: 04-04-2023
DOI: 10.1101/2023.04.04.535632
Abstract: Microbial communities found within the human gut have a strong influence on human health. Intestinal bacteria and viruses influence gastrointestinal diseases such as inflammatory bowel disease. Viruses infecting bacteria, known as bacteriophages, play a key role in modulating bacterial communities within the human gut. However, the identification and characterisation of novel bacteriophages remain a challenge. Available tools use similarities between sequences, nucleotide composition, and the presence of viral genes roteins. Most available tools consider in idual contigs to determine whether they are of viral origin. As a result of the challenges in viral assembly, fragmentation of viral genomes can occur, leading to the need for new approaches in viral identification. We introduce Phables, a new computational method to resolve bacteriophage genomes from fragmented viral metagenomic assemblies. Phables identifies bacteriophage-like components in the assembly graph, models each component as a flow network, and uses graph algorithms and flow decomposition techniques to identify genomic paths. Experimental results of viral metagenomic s les obtained from different environments show that over 80% of the bacteriophage genomes resolved by Phables have high quality and are longer than the in idual contigs identified by existing viral identification tools. Phables is available on GitHub at github.com/Vini2 hables (DOI: 10.5281/zenodo.7645166). vijini.mallawaarachchi@flinders.edu.au
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2021
DOI: 10.1101/2021.06.03.446868
Abstract: Most bacterial genomes contain integrated bacteriophages—prophages—in various states of decay. Many are active and able to excise from the genome and replicate, while others are cryptic prophages, remnants of their former selves. Over the last two decades, many computational tools have been developed to identify the prophage components of bacterial genomes, and it is a particularly active area for the application of machine learning approaches. However, progress is hindered and comparisons thwarted because there are no manually curated bacterial genomes that can be used to test new prophage prediction algorithms. Here, we present a library of gold-standard bacterial genome annotations that include manually curated prophage annotations, and a computational framework to compare the predictions from different algorithms. We use this suite to compare all extant stand-alone prophage prediction algorithms to identify their strengths and weaknesses. We provide a FAIR dataset for prophage identification, and demonstrate the accuracy, precision, recall, and f 1 score from the analysis of seven different algorithms for the prediction of prophages. We discuss caveats and concerns in this analysis and how those concerns may be mitigated.
Publisher: Cold Spring Harbor Laboratory
Date: 26-06-2022
DOI: 10.1101/2022.06.23.497420
Abstract: Flow cytometry is an established method for the detection and enumeration of viruses. However, the technique is unable to target specific viral species. Here, we present OligoFlow, a novel method for the rapid detection and enumeration of viruses by incorporating flow cytometry with species specific oligonucleotide hybridization. Using Ostried herpesvirus and dengue virus as model organisms, we demonstrate high-level detection and specificity. Our results represent a significant advancement in viral flow cytometry, opening the possibilities for the rapid identification of viruses in time critical settings.
Publisher: MDPI AG
Date: 08-05-2022
DOI: 10.3390/MICROORGANISMS10050985
Abstract: Acinetobacter baumannii is an opportunistic human pathogen responsible for numerous severe nosocomial infections. Genome analysis on the A. baumannii clinical isolate 04117201 revealed the presence of 13 two-component signal transduction systems (TCS). Of these, we examined the putative TCS named here as StkSR. The stkR response regulator was deleted via homologous recombination and its progeny, ΔstkR, was phenotypically characterized. Antibiogram analyses of ΔstkR cells revealed a two-fold increase in resistance to the clinically relevant polymyxins, colistin and polymyxin B, compared to wildtype. PAGE-separation of silver stained purified lipooligosaccharide isolated from ΔstkR and wildtype cells ruled out the complete loss of lipooligosaccharide as the mechanism of colistin resistance identified for ΔstkR. Hydrophobicity analysis identified a phenotypical change of the bacterial cells when exposed to colistin. Transcriptional profiling revealed a significant up-regulation of the pmrCAB operon in ΔstkR compared to the parent, associating these two TCS and colistin resistance. These results reveal that there are multiple levels of regulation affecting colistin resistance the suggested ‘cross-talk’ between the StkSR and PmrAB two-component systems highlights the complexity of these systems.
Publisher: Cold Spring Harbor Laboratory
Date: 06-03-2023
DOI: 10.1101/2023.03.05.531146
Abstract: Bacteroides, the prominent bacteria in the human gut, play a crucial role in degrading complex polysaccharides. Their abundance is influenced by phages belonging to the Crassvirales order. Despite identifying over 600 Crassvirales genomes computationally, only few have been successfully isolated. Continued efforts in isolation of more Crassvirales genomes can provide insights into phage-host-evolution and infection mechanisms. We focused on wastewater s les, as potential sources of phages infecting various Bacteroides hosts. Sequencing, assembly, and characterization of isolated phages revealed 14 complete genomes belonging to three novel Crassvirales species infecting Bacteroides cellulosilyticus WH2. These species, Kehishuvirus sp. ‘tikkala’ strain Bc01, Kolpuevirus sp. ‘frurule’ strain Bc03, and ‘Rudgehvirus jaberico’ strain Bc11, spanned two families, and three genera, displaying a broad range of virion productions. Upon testing all successfully cultured Crassvirales species and their respective bacterial hosts, we discovered that they do not exhibit co-evolutionary patterns with their bacterial hosts. Furthermore, we observed variations in gene similarity, with greater shared similarity observed within genera. However, despite belonging to different genera, the three novel species shared a unique structural gene that encodes the tail spike protein. When investigating the relationship between this gene and host interaction, we discovered evidence of purifying selection, indicating its functional importance. Moreover, our analysis demonstrated that this tail spike protein binds to the TonB-dependent receptors present on the bacterial host surface. Combining these observations, our findings provide insights into phage-host interactions and present three Crassvirales species as an ideal system for controlled infectivity experiments on one of the most dominant members of the human enteric virome. Bacteriophages play a crucial role in shaping microbial communities within the human gut. Among the most dominant bacteriophages in the human gut microbiome are Crassvirales phages, which infect Bacteroides. Despite being widely distributed, only a few Crassvirales genomes have been isolated, leading to a limited understanding of their biology, ecology, and evolution. This study isolated and characterized three novel Crassvirales genomes belonging to two different families, and three genera, but infecting one bacterial host, Bacteroides cellulosilyticus WH2. Notably, the observation confirmed the phages are not co-evolving with their bacterial hosts, rather have a shared ability to exploit similar features in their bacterial host. Additionally, the identification of a critical viral protein undergoing purifying selection and interacting with the bacterial receptors opens doors to targeted therapies against bacterial infections. Given Bacteroides role in polysaccharide degradation in the human gut, our findings advance our understanding of the phage-host interactions and could have important implications for the development of phage-based therapies. These discoveries may hold implications for improving gut health and metabolism to support overall well-being. The genomes used in this research are available on Sequence Read Archive (SRA) within the project, PRJNA737576. Bacteroides cellulosilyticus WH2, Kehishuvirus sp. ‘tikkala’ strain Bc01, Kolpuevirus sp. ‘ frurule’ strain Bc03, and ‘Rudgehvirus jaberico’ strain Bc11 are all available on GenBank with accessions NZ_CP072251.1 ( B. cellulosilyticus WH2), QQ198717 (Bc01), QQ198718 (Bc03), and QQ198719 (Bc11), and we are working on making the strains available through ATCC. The 3D protein structures for the three Crassvirales genomes are available to download at 0.25451/flinders.21946034.
Publisher: Springer Science and Business Media LLC
Date: 27-07-0027
Publisher: American Astronomical Society
Date: 03-2023
Abstract: We present the results of dark matter (DM) searches in a s le of 31 dwarf irregular (dIrr) galaxies within the field of view of the HAWC Observatory. dIrr galaxies are DM-dominated objects in which astrophysical gamma-ray emission is estimated to be negligible with respect to the secondary gamma-ray flux expected by annihilation or decay of weakly interacting massive particles (WIMPs). While we do not see any statistically significant DM signal in dIrr galaxies, we present the exclusion limits (95% C.L.) for annihilation cross section and decay lifetime for WIMP candidates with masses between 1 and 100 TeV. Exclusion limits from dIrr galaxies are relevant and complementary to benchmark dwarf Spheroidal (dSph) galaxies. In fact, dIrr galaxies are targets kinematically different from benchmark dSph, preserving the footprints of different evolution histories. We compare the limits from dIrr galaxies to those from ultrafaint and classical dSph galaxies previously observed with HAWC. We find that the constraints are comparable to the limits from classical dSph galaxies and ∼2 orders of magnitude weaker than the ultrafaint dSph limits.
Location: United States of America
No related grants have been discovered for Sarah Giles.