Pérez-Montarelo Dafne, Viedma Esther, Murcia Mercedes, Muñoz-Gallego Irene, Larrosa Nieves, Brañas Patricia, Fernández-Hidalgo Nuria, Gavaldà Joan, Almirante Benito, Chaves Fernando
Department of Microbiology, Instituto de Investigación Hospital de OctubreMadrid, Spain.
Department of Microbiology, Hospital Universitari Vall d'hebron, Universitat Autónoma de BarcelonaBarcelona, Spain.
Front Microbiol. 2017 May 19;8:917. doi: 10.3389/fmicb.2017.00917. eCollection 2017.
is a major cause of bacteremia and, even with appropriate clinical management, causes high morbidity, and mortality due to its involvement in endovascular complications and metastatic infections. Through different pathogenic and models we investigated the behavior of most relevant clonal complexes (CCs) causing endovascular complications. We analyzed 14 strains representing CC5, CC8, CC15, CC30, and CC45 that caused endovascular complications, including methicillin susceptible and resistant isolates and strains with different functionality of the global regulator. Their adherence to collagen, interaction with the endothelium, resistance to immune attack, capacity to form biofilm and virulence in the model were analyzed. CC30 and CC45 showed greater adhesion to collagen and CC8 showed a trend towards higher rate of intracellular persistence in endothelial cells. All CCs exhibited similar tolerance to neutrophil antimicrobial peptide hNP-1 and were capable of forming biofilms under static conditions. The virulence assay in the model demonstrated that CC15 and CC30 were the most and least virulent, respectively. The analysis of the genomic sequences of the most relevant virulence genes identified some CC15 specific gene patterns (absence of enterotoxins and gene) and variants (mainly in leucocidins and proteases), but did not reveal any gene or variant that could be responsible for the increased virulence detected for CC15 strains. Even though all the CCs were capable of causing endovascular complications, our results showed that different CCs are likely to produce these complications through different mechanisms which, if confirmed in more sophisticated models, would indicate the need to more specific management and therapeutic approaches.
是菌血症的主要病因,即使经过适当的临床管理,由于其参与血管内并发症和转移性感染,仍会导致高发病率和死亡率。通过不同的致病模型,我们研究了导致血管内并发症的最相关克隆复合体(CCs)的行为。我们分析了代表CC5、CC8、CC15、CC30和CC45的14株引起血管内并发症的菌株,包括甲氧西林敏感和耐药菌株以及具有不同全局调节功能的菌株。分析了它们对胶原蛋白的粘附、与内皮细胞的相互作用、对免疫攻击的抗性、形成生物膜的能力以及在模型中的毒力。CC30和CC45对胶原蛋白的粘附性更强,CC8在内皮细胞中的细胞内持续率有升高趋势。所有CCs对中性粒细胞抗菌肽hNP-1表现出相似的耐受性,并且能够在静态条件下形成生物膜。模型中的毒力测定表明,CC15和CC30分别是最具毒力和毒力最低的。对最相关毒力基因的基因组序列分析确定了一些CC15特异性基因模式(缺乏肠毒素和基因)和变体(主要在白细胞毒素和蛋白酶中),但没有发现任何基因或变体能解释CC15菌株检测到的毒力增加。尽管所有CCs都能够引起血管内并发症,但我们的结果表明,不同的CCs可能通过不同的机制产生这些并发症,如果在更复杂的模型中得到证实,将表明需要更具针对性的管理和治疗方法。