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Journal articleChatterjee S, Lekmeechai S, Constantinou N, et al., 2021,
The type III secretion system effector EspO of enterohaemorrhagic <i>Escherichia coli</i> inhibits apoptosis through an interaction with HAX-1
, CELLULAR MICROBIOLOGY, Vol: 23, ISSN: 1462-5814- Author Web Link
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- Citations: 1
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Journal articleDi Paolo M, Hewitt L, Nwankwo E, et al., 2021,
A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis (vol 12, dlab086, 2021)
, JAC-ANTIMICROBIAL RESISTANCE, Vol: 3 -
Journal articleDi Paolo M, Hewitt L, Nwankwo E, et al., 2021,
Erratum to: A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis.
, JAC Antimicrob Resist, Vol: 3[This corrects the article DOI: 10.1093/jacamr/dlab026.].
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Journal articleLarrouy-Maumus G, Katy J, katheryn H, et al., 2021,
Detection of colistin resistance in Pseudomonas aeruginosa using the MALDIxin test on the routine MALDI Biotyper Sirius mass spectrometer
, Frontiers in Microbiology, Vol: 12, ISSN: 1664-302XColistin is frequently a last resort treatment for Pseudomonas aeruginosa infections caused by multidrug-resistant (MDR) and extensively drug resistant (XDR) strains, and detection of colistin resistance is essential for the management of infected patients. Therefore, we evaluated the recently developed MALDIxin test for the detection of colistin resistance in Pseudomonas aeruginosa clinical strains using the routine matrix-assisted laser desorption ionization (MALDI) Biotyper Sirius system. The test is based on the detection by mass spectrometry of modified lipid A by the addition of 4-amino-L-arabinose (L-ara4N) molecules on one or two phosphate groups, in strains resistant to colistin. Overproduction of L-Ara4N molecules is mainly due to the constitutive activation of the histidine kinase (PmrB) or the response regulator (PmrA) following an amino-acid substitution in clinical strains. The performance of the test was determined on a panel of 14 colistin-susceptible and 14 colistin-resistant Pseudomonas aeruginosa clinical strains, the reference strain PAO1 and positive control mutants PmrB (V28G), PmrB (D172), PhoQ (D240-247) and ParR (M59I). In comparison with the broth microdilution (BMD) method, all the susceptible strains (n=14) and 8/14 colistin-resistant strains were detected in less than 1 hour, directly on whole bacteria. The remaining resistant strains (n=6) were all detected after a short pre-exposure (4h) to colistin before sample preparation. Validation of the method on a larger panel of strains will be the next step before its use in diagnostics laboratories. Our data showed that the MALDIxin test offers rapid and efficient detection of colistin resistant Pseudomonas aeruginosa and is thus a valuable diagnostics tool to control the spread of these emerging resistant strains.
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Journal articleSchrader S, Botella H, Jansen R, et al., 2021,
Multiform antimicrobial resistance from a metabolic mutation
, Science Advances, Vol: 7, Pages: 1-17, ISSN: 2375-2548A critical challenge for microbiology and medicine is how to cure infections by bacteria that survive antibiotic treatment by persistence or tolerance. Seeking mechanisms behind such high survival, we developed a forward-genetic method for efficient isolation of high24 survival mutants in any culturable bacterial species. We found that perturbation of an essential biosynthetic pathway (arginine biosynthesis) in a mycobacterium generated three distinct forms of resistance to diverse antibiotics, each mediated by induction of WhiB7— high persistence and tolerance to kanamycin, high survival upon exposure to rifampicin, and MIC-shifted resistance to clarithromycin. As little as one base change in a gene encoding a metabolic pathway component conferred multiple forms of resistance to multiple antibiotics with different targets. This extraordinary resilience may help explain how sub31 sterilizing exposure to one antibiotic in a regimen can induce resistance to others and invites development of drugs targeting the mediator of multiform resistance, WhiB7.
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Journal articleInnes AJ, Mullish BH, Ghani R, et al., 2021,
Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation
, Frontiers in Cellular and Infection Microbiology, Vol: 11<jats:p>The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% <jats:italic>versus</jats:italic> 36% <jats:italic>p</jats:italic> = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% <jats:italic>versus</jats:italic> 46%, <jats:italic>P</jats:italic> = 0.045) or experienced fever (0.29 <jats:italic>versus</jats:italic> 0.11 days, <jats:italic>P</jats:italic> = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients <jats:italic>versus</jats:italic> 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% <jats:italic>versus</jats:italic> 61.9% respectively, <jats:italic>p</jats:italic>=0.012), and higher non relapse mortality (NRM; 60.2% <jats:italic>versus</jats:italic> 16.7% respectively, <jats:italic>p</jats:italic>=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% <jats:italic>versus</jats:italic> 43.4%, <jats:ita
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Journal articleVincent CM, Beckwith EJ, Pearson WH, et al., 2021,
Infection increases activity via <i>Toll</i> dependent and independent mechanisms in <i>Drosophila melanogaster</i>
<jats:title>Abstract</jats:title><jats:p>Host behavioural changes are among the most apparent effects of infection. ‘Sickness behaviour’ can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here we use a real-time tracking and behavioural profiling platform to show that, in <jats:italic>Drosophila melanogaster</jats:italic>, many systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in several lethal infections. Using various bacteria and <jats:italic>D. melanogaster</jats:italic> immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with <jats:italic>Micrococcus luteus</jats:italic>, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the <jats:italic>Toll</jats:italic> ligand <jats:italic>spätzle</jats:italic> and Toll-pathway activity in the fat body and the brain. In contrast, increased activity after infection with <jats:italic>Francisella novicida</jats:italic>, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of either <jats:italic>spätzle</jats:italic> or the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.</jats:p>
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Journal articleFillol-Salom A, Bacigalupe R, Humphrey S, et al., 2021,
The secret life (cycle) of temperate bacteriophages
<jats:title>Abstract</jats:title><jats:p>Lysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with prophage <jats:underline>e</jats:underline>xcision followed by DNA <jats:underline>r</jats:underline>eplication and <jats:underline>p</jats:underline>ackaging (ERP) – a temporal program that is considered universal for most temperate phages. Here we report that the long-standing ERP program is an artefact of the experimentally favoured <jats:italic>Salmonella</jats:italic> phage P22 ts<jats:italic>c<jats:sub>2</jats:sub>29</jats:italic> heat-inducible mutant, and that wildtype P22 actually follows a replication-packaging-excision (RPE) program. We found that unlike P22 ts<jats:italic>c<jats:sub>2</jats:sub>29</jats:italic>, P22 delayed excision to just before it was detrimental to phage production. Thus, at minimal expense to itself, P22 has tuned the timing of excision to balance propagation with lateral transduction, powering the evolution of its host through gene transfer in the interest of self-preservation.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>Genetic analyses propose a new life cycle for temperate bacteriophages.</jats:p></jats:sec>
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Journal articleNolan LM, Cain AK, Clamens T, et al., 2021,
Identification of tse8 as a type VI secretion system toxin from pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells
, Nature Microbiology, Vol: 6, Pages: 1199-+, ISSN: 2058-5276The Type VI secretion system (T6SS) is a bacterial nanomachine that delivers toxic effectors to kill competitors or subvert some of their key functions. Here, we use transposon directed insertion–site sequencing to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found in Pseudomonas aeruginosa. This approach identified several putative toxin–immunity pairs, including Tse8–Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria that lack either one, or both, of the asparagine and glutamine transfer RNA synthases. Biochemical characterization of the interactions between Tse8 and the transamidosome components GatA, GatB and GatC suggests that the presence of Tse8 alters the fine-tuned stoichiometry of the transamidosome complex, and in vivo assays demonstrate that Tse8 limits the ability of prey cells to synthesize proteins. These data expand the range of cellular components targeted by the T6SS by identifying a T6SS toxin affecting protein synthesis and validate the use of a transposon directed insertion site sequencing–based global genomics approach to expand the repertoire of T6SS toxins in T6SS-encoding bacteria.
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Journal articleAllegretti JR, Kelly CR, Grinspan A, et al., 2021,
Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent <i>C. difficile</i> Infection
, Inflammatory Bowel Diseases, Vol: 27, Pages: 1371-1378, ISSN: 1078-0998<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement—all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Fifty patients enrolled in the study, among which 15 had Crohn’s disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn’s disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn’s disease patients (P = 0.04).</jats:p>
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