Candida albicans cell wall integrity transcription factors regulate polymicrobial biofilm formation with Streptococcus gordonii
Candida albicans cell wall integrity transcription factors regulate polymicrobial biofilm formation with Streptococcus gordonii
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DOI：
10.7717/peerj.7870
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发表时间：
2019-10-11
期刊：
影响因子：
2.7
通讯作者：
Maddi, Abhiram
中科院分区：
文献类型：
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作者：
Chinnici, Jennifer;Yerke, Lisa;Maddi, Abhiram
多菌生物膜在口腔和全身感染中发挥着重要作用。已知口腔菌斑细菌戈登链球菌附着在白色念珠菌的菌丝细胞壁上，在生物膜中形成玉米棒状结构。然而，白念珠菌在多菌生物膜形成中的作用还不完全清楚。本研究的目的是确定白色念珠菌转录因子在调节多菌生物被膜和戈登葡萄球菌耐药性中的作用。用质谱仪测定了混合浮游培养物中白色念珠菌和戈登念珠菌分泌的蛋白质。在混合培养和与白色念珠菌混合生物膜中测定戈登葡萄球菌对氨苄西林和红霉素的耐药率。此外，还测定了影响细胞壁完整性、丝状生长和生物膜形成的45种转录因子敲除突变的戈登葡萄球菌生物膜的形成。此外，还对这些突变体在与戈尔登葡萄球菌混合生物膜中的抗生素耐受性进行了筛选。对分泌蛋白质组的分析导致鉴定出混合培养物中唯一分泌的蛋白质。抗生素测试表明，与单一培养相比，戈登葡萄球菌在含有抗生素的混合浮游培养物中的存活率显著提高。白念珠菌转录因子SFL2、BRG1、Leu3、Cas5、Cta4、Tec1、Tup1、Rim101和Efg1的突变对混合生物膜的形成有显著影响。此外，戈登葡萄球菌与白色念珠菌转录因子突变株Tec1和SFL2的混合生物膜与对照培养物相比，显著降低了抗生素耐受性。我们的数据表明，白色念珠菌可能在混合生物膜的形成以及戈登葡萄球菌在多菌生物膜中的耐药性中起着重要作用。白色念珠菌可能会起到促进作用，而不仅仅是口腔生物膜和感染的无辜旁观者。
Polymicrobial biofilms play important roles in oral and systemic infections. The oral plaque bacterium Streptococcus gordonii is known to attach to the hyphal cell wall of the fungus Candida albicans to form corn-cob like structures in biofilms. However, the role of C. albicans in formation of polymicrobial biofilms is not completely understood. The objective of this study was to determine the role of C. albicans transcription factors in regulation of polymicrobial biofilms and antibiotic tolerance of S. gordonii. The proteins secreted by C. albicans and S. gordonii in mixed planktonic cultures were determined using mass spectrometry. Antibiotic tolerance of S. gordonii to ampicillin and erythromycin was determined in mixed cultures and mixed biofilms with C. albicans. Additionally, biofilm formation of S. gordonii with C. albicans knock-out mutants of 45 transcription factors that affect cell wall integrity, filamentous growth and biofilm formation was determined. Furthermore, these mutants were also screened for antibiotic tolerance in mixed biofilms with S. gordonii. Analysis of secreted proteomes resulted in the identification of proteins being secreted exclusively in mixed cultures. Antibiotic testing showed that S. gordonii had significantly increased survival in mixed planktonic cultures with antibiotics as compared to single cultures. C. albicans mutants of transcription factors Sfl2, Brg1, Leu3, Cas5, Cta4, Tec1, Tup1, Rim101 and Efg1 were significantly affected in mixed biofilm formation. Also mixed biofilms of S. gordonii with mutants of C. albicans transcription factors, Tec1 and Sfl2, had significantly reduced antibiotic tolerance as compared to control cultures. Our data indicates that C. albicans may have an important role in mixed biofilm formation as well as antibiotic tolerance of S. gordonii in polymicrobial biofilms. C. albicans may play a facilitating role than being just an innocent bystander in oral biofilms and infections.