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Journal articleBudden KF, Shukla SD, Rehman SF, et al., 2019,
Functional effects of the microbiota in chronic respiratory disease
, Lancet Respiratory Medicine, Vol: 7, Pages: 907-920, ISSN: 2213-2600The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.
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Journal articleAllegretti JR, Mullish B, Nativ L, et al., 2019,
185 Evaluating Dynamics of Bile Acid Metabolism to Predict Recurrence of Clostridioides difficile Infection
, American Journal of Gastroenterology, Vol: 114, Pages: S113-S113, ISSN: 0002-9270 -
Journal articleAllegretti JR, Mullish B, Hurtado J, et al., 2019,
837 Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection
, American Journal of Gastroenterology, Vol: 114, Pages: S484-S485, ISSN: 0002-9270 -
Journal articleMullish BH, McDonald JAK, Pechlivanis A, et al., 2019,
Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent <i>Clostridioides difficile</i> infection
, Gut, Vol: 68, Pages: 1791-1800, ISSN: 0017-5749<jats:sec><jats:title>Objective</jats:title><jats:p>Faecal microbiota transplant (FMT) effectively treats recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect <jats:italic>C. difficile</jats:italic> germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD genes involved in bile metabolism. Human data were validated in <jats:italic>C. difficile</jats:italic> batch cultures and a C57BL/6 mouse model of rCDI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent <jats:italic>C. difficile</jats:italic> germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered <jats:italic>bsh</jats:italic>-expressing <jats:italic>E
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Journal articleTabib-Salazar A, Mulvenna N, Severinov K, et al., 2019,
Xenogeneic regulation of the bacterial transcription machinery
, Journal of Molecular Biology, Vol: 431, Pages: 4078-4092, ISSN: 0022-2836The parasitic life cycle of viruses involves the obligatory subversion of the host's macromolecular processes for efficient viral progeny production. Viruses that infect bacteria, bacteriophages (phages), are no exception and have evolved sophisticated ways to control essential biosynthetic machineries of their bacterial prey to benefit phage development. The xenogeneic regulation of bacterial cell function is a poorly understood area of bacteriology. The activity of the bacterial transcription machinery, the RNA polymerase (RNAP), is often regulated by a variety of mechanisms involving small phage-encoded proteins. In this review, we provide a brief overview of known phage proteins that interact with the bacterial RNAP and compare how two prototypical phages of Escherichia coli, T4 and T7, use small proteins to 'puppeteer' the bacterial RNAP to ensure a successful infection.
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Journal articleHoward SA, Filloux A, 2019,
Bacterial Protein Secretion: Looking inside an injection system
, eLife, Vol: 8, Pages: 1-3, ISSN: 2050-084XThe proteins injected by bacteria into eukaryotic organisms can lead to fates as diverse as death and metamorphosis
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Journal articleFillol-Salom A, Bacarizo J, Alqasmi M, et al., 2019,
Hijacking the hijackers: escherichia coli pathogenicity islands redirect helper phage packaging for their own benefit
, Molecular Cell, Vol: 75, Pages: 1020-1030.e4, ISSN: 1097-2765Phage-inducible chromosomal islands (PICIs) represent a novel and universal class of mobile genetic elements, which have broad impact on bacterial virulence. In spite of their relevance, how the Gram-negative PICIs hijack the phage machinery for their own specific packaging and how they block phage reproduction remains to be determined. Using genetic and structural analyses, we solve the mystery here by showing that the Gram-negative PICIs encode a protein that simultaneously performs these processes. This protein, which we have named Rpp (for redirecting phage packaging), interacts with the phage terminase small subunit, forming a heterocomplex. This complex is unable to recognize the phage DNA, blocking phage packaging, but specifically binds to the PICI genome, promoting PICI packaging. Our studies reveal the mechanism of action that allows PICI dissemination in nature, introducing a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial pathogen evolution.
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Journal articleWong JLC, Romano M, Kerry LE, et al., 2019,
OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo
, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723- Author Web Link
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- Citations: 39
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Journal articlePotron A, Vuillemenot J-B, Puja H, et al., 2019,
ISAba1-dependent overexpression of eptA in clinical strains of Acinetobacter baumannii resistant to colistin
, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 74, Pages: 2544-2550, ISSN: 0305-7453- Author Web Link
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- Citations: 12
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Journal articleValentini M, Filloux A, 2019,
Multiple Roles of c-di-GMP Signaling in Bacterial Pathogenesis
, Annual Review of Microbiology, Vol: 73, Pages: 387-406, ISSN: 0066-4227The intracellular signaling molecule cyclic di-GMP (c-di-GMP) regulates the lifestyle of bacteria and controls many key functions and mechanisms. In the case of bacterial pathogens, a wide variety of virulence lifestyle factors have been shown to be regulated by c-di-GMP. Evidence of the importance of this molecule for bacterial pathogenesis has become so great that new antimicrobial agents are tested for their capacity of targeting c-di-GMP signaling. This review summarizes the current knowledge on this topic and reveals its application for the development of new antivirulence intervention strategies.
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