Protective Effect of the Golden Staphyloxanthin Biosynthesis Pathway on Staphylococcus aureus under Cold Atmospheric Plasma Treatment
Protective Effect of the Golden Staphyloxanthin Biosynthesis Pathway on Staphylococcus aureus under Cold Atmospheric Plasma Treatment
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冷大气等离子体处理下金黄色葡萄球菌黄素生物合成途径对金黄色葡萄球菌的保护作用
DOI：
10.1128/aem.01998-19
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发表时间：
2019-11
影响因子：
4.4
通讯作者：
Rao Xiancai
中科院分区：
文献类型：
--
作者：
Yang Yi;Wang Hao;Zhou Huyue;Hu Zhen;Shang Weilong;Rao Yifan;Peng Huagang;Zheng Ying;Hu Qiwen;Zhang Rong;Luo Haiyun;Rao Xiancai
金黄色葡萄球菌是一种在社区和临床环境中广泛分布的重要病原菌。多重耐药金黄色葡萄球菌的出现给葡萄球菌感染控制带来了困难。迫切需要开发具有强大杀菌效果的替代策略。冷大气等离子体(CAP)是一种很有前途的微生物灭活方法。然而，微生物失活或耐药的潜在机制还没有完全阐明。在这项研究中，我们验证了CAP对包括耐药菌株在内的金黄色葡萄球菌的杀菌作用。我们还发现，金黄色葡萄糖素及其黄色素中间体对金黄色葡萄球菌具有保护作用，早期阻断葡萄糖素合成途径可以增强金黄色葡萄球菌对CAP处理的敏感性。这些数据从细菌的角度对CAP的杀菌机制提供了深入的见解，并为预防金黄色葡萄球菌感染提供了新的靶点。摘要金黄色葡萄球菌感染严重威胁公众健康，抗生素耐药性使临床治疗复杂化，限制了解决这一问题的方法。冷大气等离子体(CAP)是一种很有前途的微生物灭活方法。然而，微生物失活或耐药的机制仍不清楚。在这项研究中，我们用自组装的CAP装置处理金黄色葡萄球菌菌株，发现CAP可以以暴露时间依赖的方式杀死金黄色葡萄球菌。此外，液体环境也会影响CAP治疗后金黄色葡萄球菌的存活率。金黄色葡萄球菌细胞在生理盐水和磷酸盐缓冲盐水中可完全灭活，但在胰酶大豆肉汤中不能灭活。扫描和透射电子显微镜显示，CAP处理的金黄色葡萄球菌细胞保持完整的形态结构，与野生型相似。重要的是，CAP处理的金黄色葡萄球菌细胞的色素表型减少。葡萄糖素生物合成基因crtm和crtN的缺失剥夺了金黄色葡萄球菌的着色能力。突变体Newman-Δcrtm和Newman-ΔcrtN对CAP处理都表现出高度的敏感性，而Newman-ΔcrtO在CAP处理后的存活率与野生型相当。我们的数据表明，葡萄糖素生物合成途径中的黄色色素中间体负责保护金黄色葡萄球菌免受CAP灭活。金黄色葡萄糖素生物合成途径中的关键酶CRTM和CrtN可能成为设计新的金黄色葡萄球菌灭菌策略的重要靶点。重要性金黄色葡萄球菌是一种重要的病原菌，在社区和临床环境中广泛分布。多重耐药金黄色葡萄球菌的出现给葡萄球菌感染控制带来了困难。迫切需要开发具有强大杀菌效果的替代策略。冷大气等离子体(CAP)是一种很有前途的微生物灭活方法。然而，微生物失活或耐药的潜在机制还没有完全阐明。在这项研究中，我们验证了CAP对包括耐药菌株在内的金黄色葡萄球菌的杀菌作用。我们还发现，金黄色葡萄糖素及其黄色素中间体对金黄色葡萄球菌具有保护作用，早期阻断葡萄糖素合成途径可以增强金黄色葡萄球菌对CAP处理的敏感性。这些数据从细菌的角度对CAP的杀菌机制提供了深入的见解，并为预防金黄色葡萄球菌感染提供了新的靶点。
Staphylococcus aureus is an important pathogen that can be widely distributed in the community and clinical settings. The emergence of S. aureus with multiple-antibiotic resistance has complicated staphylococcal infection control. The development of alternative strategies with powerful bactericidal effects is urgently needed. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. Nevertheless, the underlying mechanisms of microbial inactivation or resistance are not completely illustrated. In this study, we validated the bactericidal effects of CAP on S. aureus, including antibiotic-resistant strains. We also found that the golden staphyloxanthin, as well as its yellow pigment intermediates, protected S. aureus against CAP, and blocking the staphyloxanthin synthesis pathway at the early steps could strengthen the sensitivity of S. aureus to CAP treatment. These data provide insights into the germicidal mechanism of CAP from the aspect of bacteria and suggest new targets against S. aureus infections. ABSTRACT Staphylococcus aureus infection poses a serious threat to public health, and antibiotic resistance has complicated the clinical treatment and limited the solutions available to solve this problem. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. However, the mechanisms of microbial inactivation or resistance remain unclear. In this study, we treated S. aureus strains with a self-assembled CAP device and found that CAP can kill S. aureus in an exposure time-dependent manner. In addition, the liquid environment can influence the survival rate of S. aureus post-CAP treatment. The S. aureus cells can be completely inactivated in normal saline and phosphate-buffered saline but not in tryptic soy broth culture medium. Scanning and transmission electron microscopy revealed that the CAP-treated S. aureus cells maintained integrated morphological structures, similar to the wild-type strain. Importantly, the CAP-treated S. aureus cells exhibited a reduced pigment phenotype. Deletion of the staphyloxanthin biosynthetic genes crtM and crtN deprived the pigmentation ability of S. aureus Newman. Both the Newman-ΔcrtM and Newman-ΔcrtN mutants presented high sensitivity to CAP treatment, whereas Newman-ΔcrtO exhibited a survival rate comparable to wild-type Newman after CAP treatment. Our data demonstrated that the yellow pigment intermediates of the staphyloxanthin biosynthetic pathway are responsible for the protection of S. aureus from CAP inactivation. The key enzymes, such as CrtM and CrtN, of the golden staphyloxanthin biosynthetic pathway could be important targets for the design of novel sterilization strategies against S. aureus infections. IMPORTANCE Staphylococcus aureus is an important pathogen that can be widely distributed in the community and clinical settings. The emergence of S. aureus with multiple-antibiotic resistance has complicated staphylococcal infection control. The development of alternative strategies with powerful bactericidal effects is urgently needed. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. Nevertheless, the underlying mechanisms of microbial inactivation or resistance are not completely illustrated. In this study, we validated the bactericidal effects of CAP on S. aureus, including antibiotic-resistant strains. We also found that the golden staphyloxanthin, as well as its yellow pigment intermediates, protected S. aureus against CAP, and blocking the staphyloxanthin synthesis pathway at the early steps could strengthen the sensitivity of S. aureus to CAP treatment. These data provide insights into the germicidal mechanism of CAP from the aspect of bacteria and suggest new targets against S. aureus infections.
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DOI：
--
发表时间：
2009
期刊：
High Voltage Engineering
影响因子：
--
作者：
W. Xinxin
通讯作者：
W. Xinxin
直流气液放电等离子体对液体中浮游金黄色葡萄球菌和大肠杆菌的体外抗菌作用及机制
影响因子：
5
作者：
Xu Zimu;Cheng Cheng;Shen Jie;Lan Yan;Hu Shuheng;Han Wei;Chu Paul K.
通讯作者：
Chu Paul K.
影响因子：
--
作者：
G. Rolinson
通讯作者：
G. Rolinson
影响因子：
3.7
作者：
Maisch T;Shimizu T;Li YF;Heinlin J;Karrer S;Morfill G;Zimmermann JL
通讯作者：
Zimmermann JL
DOI：
10.1172/jci18535
发表时间：
2003-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
F. Lowy
通讯作者：
F. Lowy