S-Nitrosoglutathione Reduces the Density of Staphylococcus aureus Biofilms Established on Human Airway Epithelial Cells.
S-Nitrosoglutathione Reduces the Density of Staphylococcus aureus Biofilms Established on Human Airway Epithelial Cells.
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DOI：
10.1021/acsomega.2c06212
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发表时间：
2023-01-10
期刊：
影响因子：
4.1
通讯作者：
Sajjan, Umadevi
中科院分区：
文献类型：
--
作者：
Wolf, Alex;Tabasi, Mohsen;Zacharek, Mark;Martin, Glenn;Hershenson, Marc B.;Meyerhoff, Mark E.;Sajjan, Umadevi
慢性鼻窦炎（CRS）患者经常表现出细菌以生物膜的形式持续定植，这些生物膜对抗生素治疗具有耐药性。CRS中最常见的分离细菌之一是金黄色葡萄球菌（金黄色葡萄球菌）。一氧化氮（NO）是一种有效的抗菌剂，能有效地分散生物膜。我们假设s -亚硝基谷胱甘肽（GSNO）是一种内源性NO载体/供体，与庆大霉素协同分散和降低细菌生物膜密度。我们制备了在室温下稳定12个月的GSNO制剂，并在1小时内显示出最大的NO释放量。我们研究了该GSNO制剂对建立在囊性纤维化（CF）和CRS患者气道基底（干）细胞再生的粘膜纤毛分化气道上皮细胞顶端表面的金黄色葡萄球菌生物膜的影响。研究结果表明，对于不能产生一氧化氮的CF细胞，100 μM的GSNO处理可增加其根尖表面的一氧化氮水平，并使生物膜细菌密度降低2 log单位，而不会刺激促炎作用或诱导上皮细胞死亡。与庆大霉素联合使用，GSNO进一步增强了生物膜细菌的杀灭能力。与安慰剂相比，GSNO显著增加了感染和未感染CF细胞培养的纤毛搏动频率（CBF）。GSNO和庆大霉素联合使用还能降低CRS患者鼻上皮细胞上生长的生物膜细菌密度，改善CBF。上述结果表明，GSNO联合庆大霉素可有效降低CRS患者生物膜细菌密度。GSNO治疗也可通过改善脑血流来增强纤毛黏液清除率。
Patients with chronic rhinosinusitis (CRS) often show persistent colonization by bacteria in the form of biofilms which are resistant to antibiotic treatment. One of the most commonly isolated bacteria in CRS is Staphylococcus aureus (S. aureus). Nitric oxide (NO) is a potent antimicrobial agent and disperses biofilms efficiently. We hypothesized that S-nitrosoglutathione (GSNO), an endogenous NO carrier/donor, synergizes with gentamicin to disperse and reduce the bacterial biofilm density. We prepared GSNO formulations which are stable up to 12 months at room temperature and show the maximum amount of NO release within 1 h. We examined the effects of this GSNO formulation on the S. aureus biofilm established on the apical surface of the mucociliary-differentiated airway epithelial cell cultures regenerated from airway basal (stem) cells from cystic fibrosis (CF) and CRS patients. We demonstrate that for CF cells, which are defective in producing NO, treatment with GSNO at 100 μM increased the NO levels on the apical surface and reduced the biofilm bacterial density by 2 log units without stimulating pro-inflammatory effects or inducing epithelial cell death. In combination with gentamicin, GSNO further enhanced the killing of biofilm bacteria. Compared to placebo, GSNO significantly increased the ciliary beat frequency (CBF) in both infected and uninfected CF cell cultures. The combination of GSNO and gentamicin also reduced the bacterial density of biofilms grown on sinonasal epithelial cells from CRS patients and improved the CBF. These findings demonstrate that GSNO in combination with gentamicin may effectively reduce the density of biofilm bacteria in CRS patients. GSNO treatment may also enhance the mucociliary clearance by improving the CBF.
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影响因子：
5.7
作者：
Barraud N;Storey MV;Moore ZP;Webb JS;Rice SA;Kjelleberg S
通讯作者：
Kjelleberg S
DOI：
10.2500/ajr.2007.21.3029
发表时间：
2007-05-01
期刊：
AMERICAN JOURNAL OF RHINOLOGY
影响因子：
--
作者：
Chen, Bei;Antunes, Marcelo B.;Cohen, Noam A.
通讯作者：
Cohen, Noam A.
影响因子：
11.8
作者：
Finegold, SM;Flynn, MJ;Wynne, B
通讯作者：
Wynne, B
影响因子：
14.2
作者：
Hamilos, Daniel L.
通讯作者：
Hamilos, Daniel L.
影响因子：
2.6
作者：
Dal, T;Onerci, M;Caglar, M
通讯作者：
Caglar, M