Paredes Carina, Truong-Bolduc Que Chi, Wang Yin, Hooper David C, Ramirez-Arcos Sandra
Department of Biochemistry, Microbiology, and Immunology (BMI), Faculty of Medicine, University of Ottawa, Ottawa, ON K1G 4J5, Canada.
Donation Policy & Studies, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada.
Antibiotics (Basel). 2025 Jun 21;14(7):635. doi: 10.3390/antibiotics14070635.
: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. , a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on resistance to quinolones, which are commonly used to treat infections. : Four transfusion-relevant strains (TRSs) were subjected to comparative transcriptome analyses when grown in PCs vs. trypticase soy broth (TSB). Results of these analyses revealed differentially expressed genes involved in antibiotic resistance. Of interest, the gene (encodes for the NorB efflux pump, which is implicated in quinolone resistance and is negatively regulated by MgrA) was upregulated (1.2-4.7-fold increase) in all PC-grown TRS compared to TSB cultures. Minimal Bactericidal Concentration (MBC) of ciprofloxacin and norfloxacin in PC-grown TRS compared to TSB showed increased resistance to both quinolones in PC cultures. Complementary studies with non-transfusion-relevant strains RN6390 and its and deletion mutants were conducted. MBC of ciprofloxacin and norfloxacin and RT-qPCR assays of these strains showed that not only , but also and may be involved in enhanced quinolone resistance in PC-grown . The role of in virulence was also tested using the silkworm animal model; lethal dose 50 (LD) assays revealed slightly higher virulence in larvae infected with the wild-type strain compared to the mutant. : The PC storage environment enhances quinolone resistance in and induces differential expression of efflux pump genes. Furthermore, our preliminary data of the involvement of NorB in virulence of using a silkworm model merit further investigation with other systems such as a mammal animal model. Our results provide mechanistic insights to aid clinicians in the selection of antimicrobial treatment of patients receiving transfusions of -contaminated PCs.
血小板浓缩物（PCs）在输血医学中用于治疗出血性疾病。[具体污染物名称未给出]作为主要的PC污染物，与多种不良输血反应有关。本研究的目的是调查PC储存对[细菌名称未给出]喹诺酮类耐药性的影响，喹诺酮类药物常用于治疗[细菌名称未给出]感染。方法：将四种与输血相关的[细菌名称未给出]菌株（TRSs）分别在PCs和胰蛋白酶大豆肉汤（TSB）中培养，进行比较转录组分析。这些分析结果揭示了与抗生素耐药性相关的差异表达基因。有趣的是，[基因名称未给出]基因（编码NorB外排泵，与喹诺酮耐药性有关且受MgrA负调控）在所有在PC中生长的TRS中相对于TSB培养物上调（增加1.2 - 4.7倍）。与TSB相比，在PC中生长的TRS中，环丙沙星和诺氟沙星的最低杀菌浓度（MBC）显示对两种喹诺酮类药物的耐药性增加。对非输血相关菌株RN6390及其[基因名称未给出]和[基因名称未给出]缺失突变体进行了补充研究。这些菌株的环丙沙星和诺氟沙星MBC以及RT - qPCR分析表明，不仅[基因名称未给出]，而且[基因名称未给出]和[基因名称未给出]可能参与了在PC中生长的[细菌名称未给出]增强的喹诺酮耐药性。还使用家蚕动物模型测试了[基因名称未给出]在[细菌名称未给出]毒力中的作用；半数致死剂量（LD）测定显示，与[基因名称未给出]突变体相比，感染野生型菌株的幼虫毒力略高。结论：PC储存环境增强了[细菌名称未给出]对喹诺酮类药物的耐药性并诱导外排泵基因的差异表达。此外，我们使用家蚕模型初步证明NorB参与[细菌名称未给出]毒力的数据值得在其他系统如哺乳动物动物模型中进一步研究。我们的结果提供了机制性见解，以帮助临床医生选择接受[污染物名称未给出]污染的PC输血患者的抗菌治疗。
