Costello Anne, Reen F Jerry, O'Gara Fergal, Callaghan Máire, McClean Siobhán
Centre of Microbial Host Interactions, Centre of Applied Science for Health, Institute of Technology Tallaght, Old Blessington Road, Tallaght, Dublin 24, Ireland.
BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland.
Microbiology (Reading). 2014 Jul;160(Pt 7):1474-1487. doi: 10.1099/mic.0.074203-0. Epub 2014 Apr 30.
Cystic fibrosis (CF) is a recessive genetic disease characterized by chronic respiratory infections and inflammation causing permanent lung damage. Recurrent infections are caused by Gram-negative antibiotic-resistant bacterial pathogens such as Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and the emerging pathogen genus Pandoraea. In this study, the interactions between co-colonizing CF pathogens were investigated. Both Pandoraea and Bcc elicited potent pro-inflammatory responses that were significantly greater than Ps. aeruginosa. The original aim was to examine whether combinations of pro-inflammatory pathogens would further exacerbate inflammation. In contrast, when these pathogens were colonized in the presence of Ps. aeruginosa the pro-inflammatory response was significantly decreased. Real-time PCR quantification of bacterial DNA from mixed cultures indicated that Ps. aeruginosa significantly inhibited the growth of Burkholderia multivorans, Burkholderia cenocepacia, Pandoraea pulmonicola and Pandoraea apista, which may be a factor in its dominance as a colonizer of CF patients. Ps. aeruginosa cell-free supernatant also suppressed growth of these pathogens, indicating that inhibition was innate rather than a response to the presence of a competitor. Screening of a Ps. aeruginosa mutant library highlighted a role for quorum sensing and pyoverdine biosynthesis genes in the inhibition of B. cenocepacia. Pyoverdine was confirmed to contribute to the inhibition of B. cenocepacia strain J2315. B. multivorans was the only species that could significantly inhibit Ps. aeruginosa growth. B. multivorans also inhibited B. cenocepacia and Pa. apista. In conclusion, both Ps. aeruginosa and B. multivorans are capable of suppressing growth and virulence of co-colonizing CF pathogens.
囊性纤维化（CF）是一种隐性遗传病，其特征为慢性呼吸道感染和炎症，可导致永久性肺损伤。反复感染由革兰氏阴性耐药细菌病原体引起，如铜绿假单胞菌、洋葱伯克霍尔德菌复合体（Bcc）以及新出现的病原体潘多拉菌属。在本研究中，对共同定植的CF病原体之间的相互作用进行了调查。潘多拉菌和Bcc均引发了强烈的促炎反应，显著大于铜绿假单胞菌。最初的目的是研究促炎性病原体的组合是否会进一步加剧炎症。相反，当这些病原体在铜绿假单胞菌存在的情况下定植时，促炎反应显著降低。对混合培养物中细菌DNA的实时PCR定量分析表明，铜绿假单胞菌显著抑制了多食伯克霍尔德菌、洋葱伯克霍尔德菌、肺潘多拉菌和阿氏潘多拉菌的生长，这可能是其作为CF患者定植菌占优势的一个因素。铜绿假单胞菌无细胞上清液也抑制了这些病原体的生长，表明这种抑制是先天性的，而非对竞争者存在的反应。对铜绿假单胞菌突变体文库的筛选突出了群体感应和绿脓菌素生物合成基因在抑制洋葱伯克霍尔德菌中的作用。绿脓菌素被证实有助于抑制洋葱伯克霍尔德菌J2315菌株。多食伯克霍尔德菌是唯一能显著抑制铜绿假单胞菌生长的物种。多食伯克霍尔德菌也抑制了洋葱伯克霍尔德菌和阿氏潘多拉菌。总之，铜绿假单胞菌和多食伯克霍尔德菌都能够抑制共同定植的CF病原体的生长和毒力。
