Xu H, Sobue T, Thompson A, Xie Z, Poon K, Ricker A, Cervantes J, Diaz P I, Dongari-Bagtzoglou A
Department of Oral Health and Diagnostic Sciences, University of Connecticut Health Center, Farmington, CT, USA.
Cell Microbiol. 2014 Feb;16(2):214-31. doi: 10.1111/cmi.12216. Epub 2013 Oct 17.
Mitis-group streptococci are ubiquitous oral commensals that can promote polybacterial biofilm virulence. Using a novel murine oral mucosal co-infection model we sought to determine for the first time whether these organisms promote the virulence of C. albicans mucosal biofilms in oropharyngeal infection and explored mechanisms of pathogenic synergy. We found that Streptococcus oralis colonization of the oral and gastrointestinal tract was augmented in the presence of C. albicans. S. oralis and C. albicans co-infection significantly augmented the frequency and size of oral thrush lesions. Importantly, S. oralis promoted deep organ dissemination of C. albicans. Whole mouse genome tongue microarray analysis showed that when compared with animals infected with one organism, the doubly infected animals had genes in the major categories of neutrophilic response/chemotaxis/inflammation significantly upregulated, indicative of an exaggerated inflammatory response. This response was dependent on TLR2 signalling since oral lesions, transcription of pro-inflammatory genes and neutrophil infiltration, were attenuated in TLR2(-/-) animals. Furthermore, S. oralis activated neutrophils in a TLR2-dependent manner in vitro. In summary, this study identifies a previously unrecognized pathogenic synergy between oral commensal bacteriaand C. albicans. This is the first report of the ability of mucosal commensal bacteria to modify the virulence of an opportunistic fungal pathogen.
轻链球菌属是普遍存在的口腔共生菌，可促进多菌生物膜的毒力。我们使用一种新型小鼠口腔黏膜共感染模型，首次试图确定这些微生物是否会促进白色念珠菌口腔黏膜生物膜在口咽感染中的毒力，并探索致病协同作用的机制。我们发现，在白色念珠菌存在的情况下，口腔和胃肠道中的口腔链球菌定植会增加。口腔链球菌和白色念珠菌的共感染显著增加了鹅口疮病变的频率和大小。重要的是，口腔链球菌促进了白色念珠菌向深部器官的扩散。对小鼠全基因组舌部微阵列分析显示，与感染单一微生物的动物相比，双重感染的动物中嗜中性粒细胞反应/趋化作用/炎症等主要类别中的基因显著上调，表明炎症反应过度。这种反应依赖于TLR2信号传导，因为在TLR2（-/-）动物中，口腔病变、促炎基因转录和中性粒细胞浸润均减弱。此外，口腔链球菌在体外以TLR2依赖的方式激活中性粒细胞。总之，本研究确定了口腔共生菌与白色念珠菌之间一种以前未被认识的致病协同作用。这是关于黏膜共生菌改变机会性真菌病原体毒力能力的首次报道。
