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Journal articleSweeney E, Sabnis A, Edwards AM, et al., 2020,
Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa
, MICROBIOLOGY-SGM, Vol: 166, Pages: 1171-1180, ISSN: 1350-0872In vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in medium that mimics cystic fibrosis (CF) sputum versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and drug development pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.
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Journal articleSaromi K, England P, Tang W, et al., 2020,
Rapid glycosyl-inositol-phospho-ceramide fingerprint from filamentous fungal pathogens using the MALDI Biotyper Sirius system
, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 34, ISSN: 0951-4198- Author Web Link
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- Citations: 2
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Journal articleLin H-H, Filloux A, Lai E-M, 2020,
Role of recipient susceptibility factors during contact-dependent interbacterial competition
, Frontiers in Microbiology, Vol: 11, Pages: 1-15, ISSN: 1664-302XBacteria evolved multiple strategies to survive and develop optimal fitness in their ecological niche. They deployed protein secretion systems for robust and efficient delivery of antibacterial toxins into their target cells, therefore inhibiting their growth or killing them. To maximize antagonism, recipient factors on target cells can be recognized or hijacked to enhance the entry or toxicity of these toxins. To date, knowledge regarding recipient susceptibility (RS) factors and their mode of action is mostly originating from studies on the type Vb secretion system that is also known as the contact-dependent inhibition (CDI) system. Yet, recent studies on the type VI secretion system (T6SS), and the CDI by glycine-zipper protein (Cdz) system, also reported the emerging roles of RS factors in interbacterial competition. Here, we review these RS factors and their mechanistic impact in increasing susceptibility of recipient cells in response to CDI, T6SS, and Cdz. Past and future strategies for identifying novel RS factors are also discussed, which will help in understanding the interplay between attacker and prey upon secretion system-dependent competition. Understanding these mechanisms would also provide insights for developing novel antibacterial strategies to antagonize aggressive bacteria-killing pathogens.
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Journal articleYong HY, Larrouy-Maumus G, Zloh M, et al., 2020,
Early detection of metabolic changes in drug-induced steatosis using metabolomics approaches
, RSC ADVANCES, Vol: 10, Pages: 41047-41057- Author Web Link
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- Citations: 1
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Conference paperMiguens Blanco J, Selvarajah U, Liu Z, et al., 2020,
Identification of New Associations Between Psoriatic Arthritis and the Gut Microbiota. the Mi-PART, a Phenomic Study
, ACR Convergence 2020, Publisher: Wiley, ISSN: 2326-5205 -
Journal articleMartinez-Gili L, McDonald JAK, Liu Z, et al., 2020,
Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent <i>Clostridioides difficile</i> infection and beyond: the contribution of gut microbial-derived metabolites
, Gut Microbes, Vol: 12, Pages: 1810531-1810531, ISSN: 1949-0976 -
Journal articleHarnagel A, Quezada LL, Park SW, et al., 2020,
Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress
, MOLECULAR MICROBIOLOGY, Vol: 115, Pages: 272-289, ISSN: 0950-382X- Author Web Link
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- Citations: 10
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Journal articleMuir A, Gurung I, Cehovin A, et al., 2020,
Construction of a complete set of Neisseria meningitidis mutants and its use for the phenotypic profiling of this human pathogen.
, Nat Commun, Vol: 11The bacterium Neisseria meningitidis causes life-threatening meningitis and sepsis. Here, we construct a complete collection of defined mutants in protein-coding genes of this organism, identifying all genes that are essential under laboratory conditions. The collection, named NeMeSys 2.0, consists of individual mutants in 1584 non-essential genes. We identify 391 essential genes, which are associated with basic functions such as expression and preservation of genome information, cell membrane structure and function, and metabolism. We use this collection to shed light on the functions of diverse genes, including a gene encoding a member of a previously unrecognised class of histidinol-phosphatases; a set of 20 genes required for type IV pili function; and several conditionally essential genes encoding antitoxins and/or immunity proteins. We expect that NeMeSys 2.0 will facilitate the phenotypic profiling of a major human bacterial pathogen.
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Journal articleAllegretti JR, Kelly CR, Grinspan A, et al., 2020,
Outcomes of fecal microbiota transplantation in patients with inflammatory bowel diseases and recurrent Clostridioides difficile infection
, Gastroenterology, Vol: 159, Pages: 1982-1984, ISSN: 0016-5085There has been an increase in the burden of Clostridioides difficile infection (CDI),1 especially in high-risk populations such as patients with inflammatory bowel disease (IBD).2 The prevalence of CDI in the IBD population is up to 8-fold higher than comparable controls, with increased rates of recurrence and CDI-associated mortality.3 In addition, CDI may induce an IBD flare, and worsen disease severity and clinical course.4Fecal microbiota transplantation (FMT) is a guideline recommended therapy for recurrent CDI5; however, supportive randomized trials excluded patients with IBD. In retrospective trials of patients with IBD, FMT failure rates had been reported to be approximately 25% to 30%.6 In addition, Khoruts and colleagues reported that patients with IBD and CDI were more likely to fail FMT,7 leading to further uncertainty regarding the safety and efficacy of FMT in IBD patients with concurrent CDI. Accordingly, we conducted the first prospective study examining the efficacy of FMT among patients with IBD and CDI.MethodsWe conducted an open-label, prospective, single-arm, multicenter cohort study at 4 tertiary care FMT referral centers (Brigham and Women’s Hospital, Indiana University, Brown University, and Mount Sinai Hospital; NCT03106844). Patients with a confirmed diagnosis of IBD and 2 or more confirmed CDI episodes within 12 months, including the most recent episode occurring within 3 months, were enrolled. In keeping with CDI clinical guidelines,5 polymerase chain reaction or glutamate dehydrogenase with toxin enzyme immunoassay were permitted for the qualifying CDI episode. Patients with a total or subtotal colectomy, isolated ileal or small bowel Crohn’s disease, those pregnant or breastfeeding, those treated with vancomycin or metronidazole for more than 60 days, or those who had undergone a prior FMT within 12 months were excluded. Baseline IBD and CDI data were collected. All patients underwent a single FMT via colonoscopy. Four robus
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Journal articleShenker NS, Perdones-Montero A, Burke A, et al., 2020,
Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months
, NUTRIENTS, Vol: 12- Author Web Link
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- Citations: 2
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