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用抗坏血酸、地塞米松和碳酸氢钠来减弱从新生儿败血症中分离出来的耐药超级细菌金黄色葡萄球菌的毒力。

Attenuating the virulence of the resistant superbug Staphylococcus aureus bacteria isolated from neonatal sepsis by ascorbic acid, dexamethasone, and sodium bicarbonate.

机构信息

Microbiology and Immunology Department, Faculty of Pharmacy, Port Said University, Port Fuad, Egypt.

Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

出版信息

BMC Microbiol. 2022 Nov 9;22(1):268. doi: 10.1186/s12866-022-02684-x.

Abstract

BACKGROUND

Infections affecting neonates caused by Staphylococcus aureus are widespread in healthcare facilities; hence, novel strategies are needed to fight this pathogen. In this study, we aimed to investigate the effectiveness of the FDA-approved medications ascorbic acid, dexamethasone, and sodium bicarbonate to reduce the virulence of the resistant Staphylococcus aureus bacteria that causes neonatal sepsis and seek out suitable alternatives to the problem of multi-drug resistance.

METHODS

Tested drugs were assessed phenotypically and genotypically for their effects on virulence factors and virulence-encoding genes in Staphylococcus aureus. Furthermore, drugs were tested in vivo for their ability to reduce Staphylococcus aureus pathogenesis.

RESULTS

Sub-inhibitory concentrations (1/8 MIC) of ascorbic acid, dexamethasone, and sodium bicarbonate reduced the production of Staphylococcus aureus virulence factors, including biofilm formation, staphyloxanthin, proteases, and hemolysin production, as well as resistance to oxidative stress. At the molecular level, qRT-PCR was used to assess the relative expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes regulating virulence factors production and showed a significant reduction in the relative expression levels of all the tested genes.

CONCLUSIONS

The current findings reveal that ascorbic acid, dexamethasone, and sodium bicarbonate have strong anti-virulence effects against Staphylococcus aureus. Thus, suggesting that they might be used as adjuvants to treat infections caused by Staphylococcus aureus in combination with conventional antimicrobials or as alternative therapies.

摘要

背景

金黄色葡萄球菌引起的新生儿感染在医疗机构中广泛存在;因此,需要新的策略来对抗这种病原体。在这项研究中,我们旨在研究已获美国食品和药物管理局批准的药物抗坏血酸、地塞米松和碳酸氢钠降低导致新生儿败血症的耐药金黄色葡萄球菌毒力的效果,并寻找解决多药耐药问题的合适替代品。

方法

对测试药物进行表型和基因型评估,以研究其对金黄色葡萄球菌毒力因子和毒力编码基因的影响。此外,还在体内测试了药物降低金黄色葡萄球菌发病机制的能力。

结果

亚抑菌浓度(1/8 MIC)的抗坏血酸、地塞米松和碳酸氢钠降低了金黄色葡萄球菌毒力因子的产生,包括生物膜形成、金葡素、蛋白酶和溶血素的产生以及对氧化应激的抵抗力。在分子水平上,使用 qRT-PCR 评估了调节毒力因子产生的 crtM、sigB、sarA、agrA、hla、fnbA 和 icaA 基因的相对表达水平,结果显示所有测试基因的相对表达水平均显著降低。

结论

目前的研究结果表明,抗坏血酸、地塞米松和碳酸氢钠对金黄色葡萄球菌具有很强的抗毒力作用。因此,它们可能被用作与传统抗菌药物联合治疗金黄色葡萄球菌感染的辅助药物,或作为替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fe9/9644464/e151b1aa1225/12866_2022_2684_Fig1_HTML.jpg

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