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  • 1
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 1 ( 2022-01-18)
    Abstract: Neisseria gonorrhoeae is an increasing public health threat due to its rapidly rising incidence and antibiotic resistance. There are an estimated 106 million cases per year worldwide, there is no vaccine available to prevent infection, and N. gonorrhoeae strains that are resistant to all antibiotics routinely used to treat the infection have emerged. In many strains, antibiotic resistance is mediated by overexpression of the MtrCDE efflux pump, which enables the bacteria to transport toxic antibiotics out of the cell. Genetic mutations that inactivate MtrCDE have previously been shown to render resistant strains susceptible to certain antibiotics. Here, we show that peptides rationally designed to target and disrupt the activity of each of the three protein components of MtrCDE were able to increase the susceptibility of N. gonorrhoeae strains to antibiotics in a dose-dependent manner and with no toxicity to human cells. Cotreatment of bacteria with subinhibitory concentrations of the peptide led to 2- to 64-fold increases in susceptibility to erythromycin, azithromycin, ciprofloxacin, and/or ceftriaxone in N. gonorrhoeae strains FA1090, WHO K, WHO P, and WHO X. The cotreatment experiments with peptides P-MtrC1 and P-MtrE1 resulted in increased susceptibilities of WHO P and WHO X to azithromycin, ciprofloxacin, and ceftriaxone that were of the same magnitude seen in MtrCDE mutants. P-MtrE1 was able to change the azithromycin resistance profile of WHO P from resistant to susceptible. Data presented here demonstrate that these peptides may be developed for use as a dual treatment with existing antibiotics to treat multidrug-resistant gonococcal infections.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 220.31-220.31
    Abstract: ABO compatible allogeneic blood transfusion (ABT) is associated with transfusion-related immune modulation (TRIM) and poor patient outcomes including perioperative infection and myocardial infarction. Intraoperative cell salvage (ICS) enables collection, processing and reinfusion of autologous blood lost during surgery. We investigated whether immune suppression associated with ABT could be reduced by using ICS. Suitable orthopaedic patients were consented and recruited to the study (n=20, HREC/17/QRBW/685). 10mL anticoagulated blood (EDTA) was collected from the patient (pre-operatively) and from the ICS blood product. An established whole blood culture model was used to assess changes to monocyte and myeloid dendritic cell (mDC) inflammatory responses (intracellular cytokine staining for IL-6, IL-8, IL-10, IL-12, IL-1α, TNF-α, MIP-1α, MIP-1β, MCP-1, IP-10) following exposure of the patient’s pre-operative blood to ABO compatible allogenic blood (Blood Service, Kelvin Grove) or their ICS blood (P & lt;0.05 ANOVA). Exposure to ABT significantly suppressed the inflammatory response of both mDC (IL-10, IL-12, IL-1α, IL-8, TNF-a, MIP-α, MIP-1β) and monocytes (IL-10, IL-6, IL-12, IL-1α, IL-8, IL-10, IL-12, TNF-α and MIP-1α). Compared to ABT, exposure to the patients’ own (ICS) blood improved mDC IL-8, IL-10, IL-12, TNF-α and MIP-1α production and monocyte IL-10 and MIP-1β production. We provide in vitro evidence that ICS may reduce ABT associated adverse outcomes associated with improved inflammatory response and immune competence post-transfusion.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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