Waite Richard D, Qureshi Muhammad R, Whiley Robert A
Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
PLoS One. 2017 Mar 16;12(3):e0173741. doi: 10.1371/journal.pone.0173741. eCollection 2017.
Cystic fibrosis (CF) airways harbour complex and dynamic polymicrobial communities that include many oral bacteria. Despite increased knowledge of CF airway microbiomes the interaction between established CF pathogens and other resident microbes and resulting impact on disease progression is poorly understood. Previous studies have demonstrated that oral commensal streptococci of the Anginosus group (AGS) can establish chronic pulmonary infections and become numerically dominant in CF sputa indicating that they play an important role in CF microbiome dynamics. In this study a strain of Pseudomonas aeruginosa (DWW2) of the mucoid alginate overproducing phenotype associated with chronic CF airway infection and a strain of the oral commensal AGS species Streptococcus anginosus (3a) from CF sputum were investigated for their ability to co-exist and their responses to biofilm co-culture. Bacteria in biofilms were quantified, pyocyanin expression by DWW2 was measured and the effect of AGS strain 3a on reversion of DWW2 to a non-mucoidal phenotype investigated. The virulence of DWW2, 3a and colony variant phenotypes of DWW2 in mono- and co-culture were compared in a Galleria mellonella infection model. Co-culture biofilms were formed in normoxic, hypercapnic (10% CO2) and anoxic atmospheres with the streptococcus increasing in number in co-culture, indicating that these bacteria would be able to co-exist and thrive within the heterogeneous microenvironments of the CF airway. The streptococcus caused increased pyocyanin expression by DWW2 and colony variants by stimulating reversion of the mucoid phenotype to the high pyocyanin expressing non-mucoid phenotype. The latter was highly virulent in the infection model with greater virulence when in co-culture with the streptococcus. The results of this study demonstrate that the oral commensal S. anginosus benefits from interaction with P. aeruginosa of the CF associated mucoid phenotype and modulates the behaviour of the pseudomonad in ways that may be clinically relevant.
囊性纤维化（CF）气道中存在复杂且动态的多微生物群落，其中包括许多口腔细菌。尽管对CF气道微生物群的了解有所增加，但已确定的CF病原体与其他常驻微生物之间的相互作用以及对疾病进展的影响仍知之甚少。先前的研究表明，咽峡炎链球菌群（AGS）的口腔共生链球菌可引发慢性肺部感染，并在CF痰液中数量占优，这表明它们在CF微生物群动态变化中起重要作用。在本研究中，对一株与慢性CF气道感染相关的黏液性藻酸盐过度产生表型的铜绿假单胞菌（DWW2）和一株来自CF痰液的口腔共生AGS菌种咽峡炎链球菌（3a）的共存能力及其对生物膜共培养的反应进行了研究。对生物膜中的细菌进行定量，测量DWW2的绿脓菌素表达，并研究AGS菌株3a对DWW2向非黏液性表型逆转的影响。在大蜡螟感染模型中比较了DWW2、3a以及DWW2在单培养和共培养中的菌落变异表型的毒力。在常氧、高碳酸血症（10%二氧化碳）和缺氧环境中形成共培养生物膜，共培养时链球菌数量增加，表明这些细菌能够在CF气道的异质微环境中共存并生长。链球菌通过刺激黏液性表型逆转为高绿脓菌素表达的非黏液性表型，导致DWW2的绿脓菌素表达增加和菌落变异。后者在感染模型中具有高毒力，与链球菌共培养时毒力更强。本研究结果表明，口腔共生的咽峡炎链球菌受益于与CF相关黏液性表型的铜绿假单胞菌的相互作用，并以可能与临床相关的方式调节假单胞菌的行为。
