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  1. Article ; Online: Discovery, mode of action and secretion of

    Petrova, Yoana D / Mahenthiralingam, Eshwar

    Cell surface (Amsterdam, Netherlands)

    2022  Volume 8, Page(s) 100081

    Abstract: ... ...

    Abstract Burkholderia
    Language English
    Publishing date 2022-10-13
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2468-2330
    ISSN (online) 2468-2330
    DOI 10.1016/j.tcsw.2022.100081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Hidden Genomic Diversity, Specialized Metabolite Capacity, and Revised Taxonomy of

    Mullins, Alex J / Mahenthiralingam, Eshwar

    Frontiers in microbiology

    2021  Volume 12, Page(s) 726847

    Abstract: ... ...

    Abstract Burkholderia
    Language English
    Publishing date 2021-09-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.726847
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Polyyne-producing

    Webster, Gordon / Mullins, Alex J / Petrova, Yoana D / Mahenthiralingam, Eshwar

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1240206

    Abstract: Extensive crop losses are caused by oomycete and fungal damping-off diseases. Agriculture relies heavily on chemical pesticides to control disease, but due to safety concerns multiple agents have been withdrawn. ...

    Abstract Extensive crop losses are caused by oomycete and fungal damping-off diseases. Agriculture relies heavily on chemical pesticides to control disease, but due to safety concerns multiple agents have been withdrawn.
    Language English
    Publishing date 2023-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1240206
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Identification of two distinct phylogenomic lineages and model strains for the understudied cystic fibrosis lung pathogen

    Parfitt, Kasia M / Green, Angharad E / Connor, Thomas R / Neill, Daniel R / Mahenthiralingam, Eshwar

    Microbiology (Reading, England)

    2023  Volume 169, Issue 8

    Abstract: Burkholderia ... ...

    Abstract Burkholderia multivorans
    MeSH term(s) Animals ; Mice ; Burkholderia/classification ; Burkholderia/genetics ; Burkholderia Infections/complications ; Burkholderia Infections/microbiology ; Cystic Fibrosis/complications ; Cystic Fibrosis/microbiology ; Multilocus Sequence Typing ; Phylogeny ; Genome, Bacterial/genetics ; Mice, Inbred BALB C ; Female
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.001366
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  5. Article ; Online: Emerging cystic fibrosis pathogens and the microbiome.

    Mahenthiralingam, Eshwar

    Paediatric respiratory reviews

    2014  Volume 15 Suppl 1, Page(s) 13–15

    Abstract: Cystic fibrosis (CF) respiratory infection is characterised by the presence of typical human bacterial pathogens such as Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus. Less typical pathogens such as Burkholderia, ... ...

    Abstract Cystic fibrosis (CF) respiratory infection is characterised by the presence of typical human bacterial pathogens such as Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus. Less typical pathogens such as Burkholderia, Stenotrophomonas, Achromobacter, Pandorea and Ralstonia have emerged as problematic infections which are largely unique to people with CF. Using molecular methods, two groups of anaerobic bacteria Prevotella species and the Streptococcus milleri group have also recently been shown to be highly prevalent in CF sputum. Collectively, the diversity of microorganisms present in respiratory specimens has been designated the CF microbiome. The challenges posed by emerging CF pathogens and a microbiome-based view of CF infection are discussed in terms of their impact on clinical outcome, diagnosis and therapy.
    MeSH term(s) Cystic Fibrosis/microbiology ; Humans ; Microbiota
    Language English
    Publishing date 2014-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2147664-0
    ISSN 1526-0550 ; 1526-0542
    ISSN (online) 1526-0550
    ISSN 1526-0542
    DOI 10.1016/j.prrv.2014.04.006
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  6. Article ; Online: Implementation of microbiota analysis in clinical trials for cystic fibrosis lung infection: Experience from the OligoG phase 2b clinical trials.

    Weiser, Rebecca / Rye, Philip D / Mahenthiralingam, Eshwar

    Journal of microbiological methods

    2021  Volume 181, Page(s) 106133

    Abstract: Culture-independent microbiota analysis is widely used in research and being increasingly used in translational studies. However, methods for standardisation and application of these analyses in clinical trials are limited. Here we report the microbiota ... ...

    Abstract Culture-independent microbiota analysis is widely used in research and being increasingly used in translational studies. However, methods for standardisation and application of these analyses in clinical trials are limited. Here we report the microbiota analysis that accompanied two phase 2b clinical trials of the novel, non-antibiotic therapy OligoG CF-5/20 for cystic fibrosis (CF) lung infection. Standardised protocols (DNA extraction, PCR, qPCR and 16S rRNA gene sequencing analysis) were developed for application to the Pseudomonas aeruginosa (NCT02157922) and Burkholderia cepacia complex (NCT02453789) clinical trials involving 45 and 13 adult trial participants, respectively. Microbiota analysis identified that paired sputum samples from an individual participant, taken within 2 h of each other, had reproducible bacterial diversity profiles. Although culture microbiology had identified patients as either colonised by P. aeruginosa or B. cepacia complex species at recruitment, microbiota analysis revealed patient lung infection communities were not always dominated by these key CF pathogens. Microbiota profiles were patient-specific and remained stable over the course of both clinical trials (6 sampling points over the course of 140 days). Within the Burkholderia trial, participants were infected with B. cenocepacia (n = 4), B. multivorans (n = 6), or an undetermined species (n = 3). Colonisation with either B. cenocepacia or B. multivorans influenced the overall bacterial community structure in sputum. Overall, we have shown that sputum microbiota in adults with CF is stable over a 2 h time-frame, suggesting collection of a single sample on a collection day is sufficient to capture the microbiota diversity. Despite the uniform pathogen culture-positivity status at recruitment, trial participants were highly heterogeneous in their lung microbiota. Understanding the microbiota profiles of individuals with CF ahead of future clinical trials would be beneficial in the context of patient stratification and trial design.
    MeSH term(s) Adult ; Burkholderia cepacia complex/isolation & purification ; Cystic Fibrosis/microbiology ; Double-Blind Method ; Female ; Humans ; Lung/microbiology ; Male ; Microbiota ; Middle Aged ; Pseudomonas aeruginosa/isolation & purification ; Sputum/microbiology ; Young Adult
    Language English
    Publishing date 2021-01-07
    Publishing country Netherlands
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 604916-3
    ISSN 1872-8359 ; 0167-7012
    ISSN (online) 1872-8359
    ISSN 0167-7012
    DOI 10.1016/j.mimet.2021.106133
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  7. Article ; Online: Construction and evaluation of a bioluminescent

    Rushton, Laura / Donoghue, Denise / Bull, Matthew / Jay, Peter / Mahenthiralingam, Eshwar

    Microbiology (Reading, England)

    2021  Volume 167, Issue 8

    Abstract: Preservative efficacy testing (PET) is a fundamental practice in industrial microbiology used to ensure product shelf-life and quality. To improve on current growth-based PET, bioluminescence was evaluated as a real-time bacterial viability indicator ... ...

    Abstract Preservative efficacy testing (PET) is a fundamental practice in industrial microbiology used to ensure product shelf-life and quality. To improve on current growth-based PET, bioluminescence was evaluated as a real-time bacterial viability indicator using
    MeSH term(s) Anti-Bacterial Agents ; Bacteria ; Ciprofloxacin ; Preservatives, Pharmaceutical ; Pseudomonas aeruginosa/genetics
    Chemical Substances Anti-Bacterial Agents ; Preservatives, Pharmaceutical ; Ciprofloxacin (5E8K9I0O4U)
    Language English
    Publishing date 2021-09-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.001072
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  8. Article ; Online: Novel application of metagenomics for the strain-level detection of bacterial contaminants within non-sterile industrial products - a retrospective, real-time analysis.

    Cunningham-Oakes, Edward / Pointon, Tom / Murphy, Barry / Campbell-Lee, Stuart / Connor, Thomas R / Mahenthiralingam, Eshwar

    Microbial genomics

    2023  Volume 8, Issue 11

    Abstract: The home and personal care (HPC) industry generally relies on initial cultivation and subsequent biochemical testing for the identification of microorganisms in contaminated products. This process is slow (several days for growth), labour intensive, and ... ...

    Abstract The home and personal care (HPC) industry generally relies on initial cultivation and subsequent biochemical testing for the identification of microorganisms in contaminated products. This process is slow (several days for growth), labour intensive, and misses organisms which fail to revive from the harsh environment of preserved consumer products. Since manufacturing within the HPC industry is high-throughput, the process of identification of microbial contamination could benefit from the multiple cultivation-independent methodologies that have developed for the detection and analysis of microbes. We describe a novel workflow starting with automated DNA extraction directly from a HPC product, and subsequently applying metagenomic methodologies for species and strain-level identification of bacteria. The workflow was validated by application to a historic microbial contamination of a general-purpose cleaner (GPC). A single strain of
    MeSH term(s) Retrospective Studies ; Bacteria/genetics ; Metagenome ; Metagenomics/methods ; Workflow
    Language English
    Publishing date 2023-02-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.000884
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  9. Article ; Online: A 2.8 Å Structure of Zoliflodacin in a DNA Cleavage Complex with

    Morgan, Harry / Lipka-Lloyd, Magdalena / Warren, Anna J / Hughes, Naomi / Holmes, John / Burton, Nicolas P / Mahenthiralingam, Eshwar / Bax, Ben D

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: Since 2000, some thirteen quinolones and fluoroquinolones have been developed and have come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA cleavage complexes with DNA gyrase and topoisomerase IV (topo ... ...

    Abstract Since 2000, some thirteen quinolones and fluoroquinolones have been developed and have come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA cleavage complexes with DNA gyrase and topoisomerase IV (topo IV), the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here, we report on a 2.8 Å X-ray crystal structure, which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA cleavage site(s) as quinolones, sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water-metal ion bridge to GyrA), suggesting it may be more difficult for bacteria to develop target mediated resistance. We show that zoliflodacin has an MIC of 4 µg/mL against
    MeSH term(s) Humans ; DNA Gyrase/metabolism ; Staphylococcus aureus/metabolism ; DNA Topoisomerase IV/genetics ; DNA Cleavage ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Quinolones/pharmacology ; Fluoroquinolones ; Topoisomerase II Inhibitors/pharmacology ; Staphylococcal Infections ; Bacteria/metabolism ; Microbial Sensitivity Tests ; DNA Topoisomerases, Type II/metabolism
    Chemical Substances DNA Gyrase (EC 5.99.1.3) ; zoliflodacin (FWL2263R77) ; DNA Topoisomerase IV (EC 5.99.1.-) ; Anti-Bacterial Agents ; Quinolones ; Fluoroquinolones ; Topoisomerase II Inhibitors ; DNA Topoisomerases, Type II (EC 5.99.1.3)
    Language English
    Publishing date 2023-01-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021634
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  10. Article: A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients.

    Roberts, Aled E L / Xanthe, Cendl / Hopkins, Alison L / Bodger, Owen / Lewis, Paul / Mahenthiralingam, Eshwar / Duckers, Jamie / Jenkins, Rowena E

    Pilot and feasibility studies

    2022  Volume 8, Issue 1, Page(s) 216

    Abstract: Background: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a ... ...

    Abstract Background: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load.
    Methods: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity.
    Discussion: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies.
    Trial registration: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks.
    Trial registration number: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered).
    Language English
    Publishing date 2022-09-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2809935-7
    ISSN 2055-5784
    ISSN 2055-5784
    DOI 10.1186/s40814-022-01175-0
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