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  • Hannaway, Rachel F  (4)
  • 1
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  Transactions of The Royal Society of Tropical Medicine and Hygiene Vol. 113, No. 10 ( 2019-10-11), p. 641-648
    In: Transactions of The Royal Society of Tropical Medicine and Hygiene, Oxford University Press (OUP), Vol. 113, No. 10 ( 2019-10-11), p. 641-648
    Kurzfassung: Enteric fever is common in southeast Asia. However, there is little information on the circulating Salmonella enterica strains causing enteric fever in Myanmar. Methods We performed antimicrobial susceptibility testing and whole genome sequencing on S. enterica bloodstream isolates from febrile patients aged ≥12 y attending two hospitals in Yangon, Myanmar, from 5 October 2015 through 4 October 2016. We identified the serovar of S. enterica, determined antimicrobial susceptibility and the molecular mechanisms of resistance. We analysed phylogenetic relationships among Myanmar S. enterica isolates and those with isolates from neighbouring countries. Results Of 73 S. enterica isolated, 39 (53%) were serovar Typhi and 34 (47%) were Paratyphi A. All isolates were susceptible to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole but resistant to ciprofloxacin. We identified mutations in chromosomal genes gyrA, gyrB and parC as responsible for fluoroquinolone resistance. All S. enterica Typhi isolates were of 4.3.1 subclade (formerly known as H58) and formed two closely related genotypic clusters; both clusters were most closely related to isolates from India from 2012. All S. enterica Paratyphi A were lineage C, clade C4 and were closely related. Conclusion Our study describes currently circulating S. enterica serovars in Myanmar, the genetic basis of their antimicrobial resistance and provides a genotypic framework for epidemiologic study.
    Materialart: Online-Ressource
    ISSN: 0035-9203 , 1878-3503
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2135136-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: European Journal of Immunology, Wiley, Vol. 50, No. 2 ( 2020-02), p. 178-191
    Kurzfassung: Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co‐stimulatory signals, such as TLR agonists, that can modulate TCR‐mediated activation. Recently, type I interferons (T1‐IFNs) have been identified as contributing to cytokine‐mediated MAIT cell activation. However, it is unknown whether T1‐IFNs also have a role during TCR‐mediated MAIT cell activation. In this study, we investigated the co‐stimulatory role of T1‐IFNs during TCR‐mediated activation of MAIT cells by the MR1 ligand 5‐amino‐6‐ d ‐ribitylaminouracil/methylglyoxal. We found that T1‐IFNs were able to boost interferon‐γ and granzyme B production in 5‐amino‐6‐ d ‐ribitylaminouracil/methylglyoxal‐stimulated MAIT cells. Similarly, influenza virus‐induced T1‐IFNs enhanced TCR‐mediated MAIT cell activation. An essential role of T1‐IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co‐stimulatory role of T1‐IFNs was also evident in liver‐derived MAIT cells. T1‐IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1‐IFNs during TCR‐mediated MAIT cell activation.
    Materialart: Online-Ressource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2020
    ZDB Id: 1491907-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), ( 2019-04-08)
    Kurzfassung: A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed “early clearance.” Methods Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive. Results Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae. Conclusions Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.
    Materialart: Online-Ressource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 1473843-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2021
    In:  JAC-Antimicrobial Resistance Vol. 3, No. 4 ( 2021-09-30)
    In: JAC-Antimicrobial Resistance, Oxford University Press (OUP), Vol. 3, No. 4 ( 2021-09-30)
    Kurzfassung: The incidence of infections with ESBL-producing Escherichia coli (ESBL-Ec) in New Zealand is increasing. ESBL-Ec most commonly cause urinary tract infections and are seen in both community and hospitalized patients. The reason for the increasing incidence of ESBL-Ec infections is unknown. Methods In this study, 65 urinary ESBL-Ec isolates from the Otago region in 2015 were fully genetically characterized to understand the mechanisms of transmission. The ESBL gene, E. coli STs, plasmid types and genetic context (e.g. insertion sequences) of ESBL genes were determined by a combination of whole genome and plasmid sequencing. The phylogenetic relationships of the isolates were compared with ESBL-Ec isolates sequenced as part of the 2016 nationwide survey. Results Significant diversity of E. coli strains, plasmids, and the genetic context of ESBL genes was seen. However, there was evidence of common mobile genetic elements in unrelated ESBL-Ec. Conclusions Multiple introductions of ESBL resistance genes or resistant bacterial strains with limited horizontal transmission of mobile genetic elements accounts for the increased incidence of ESBL-Ec in this low prevalence area. Future studies should investigate modes of transmission of ESBL-Ec in the Otago region.
    Materialart: Online-Ressource
    ISSN: 2632-1823
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2973194-X
    Standort Signatur Einschränkungen Verfügbarkeit
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