Morales-Laverde Liliana, Trobos Margarita, Echeverz Maite, Solano Cristina, Lasa Iñigo
Laboratory of Microbial Pathogenesis. Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, 31008, Spain.
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg. Gothenburg, Sweden.
Biofilm. 2022 Nov 8;4:100093. doi: 10.1016/j.bioflm.2022.100093. eCollection 2022 Dec.
is a leading cause of prosthetic joint infections (PJI). Surface adhesins play an important role in the primary attachment to plasma proteins that coat the surface of prosthetic devices after implantation. Previous efforts to identify a genetic component of the bacterium that confers an enhanced capacity to cause PJI have focused on gene content, kmers, or single-nucleotide polymorphisms (SNPs) in coding sequences. Here, using a collection of strains isolated from PJI and wounds, we investigated whether genetic variations in the regulatory region of genes encoding surface adhesins lead to differences in their expression levels and modulate the capacity of to colonize implanted prosthetic devices. The data revealed that isolates from the same clonal complex (CC) contain a specific pattern of SNPs in the regulatory region of genes encoding surface adhesins. As a consequence, each clonal lineage shows a specific profile of surface proteins expression. Co-infection experiments with representative isolates of the most prevalent CCs demonstrated that some lineages have a higher capacity to colonize implanted catheters in a murine infection model, which correlated with a greater ability to form a biofilm on coated surfaces with plasma proteins. Together, results indicate that differences in the expression level of surface adhesins may modulate the propensity of strains to cause PJI. Given the high conservation of surface proteins among staphylococci, our work lays the framework for investigating how diversification at intergenic regulatory regions affects the capacity of to colonize the surface of medical implants.
是人工关节感染（PJI）的主要原因。表面黏附素在与植入后覆盖人工装置表面的血浆蛋白的初始附着过程中起重要作用。先前为鉴定赋予细菌增强的引起PJI能力的遗传成分所做的努力集中在基因内容、短序列片段或编码序列中的单核苷酸多态性（SNP）上。在这里，我们使用从PJI和伤口分离的一系列菌株，研究编码表面黏附素的基因调控区域的遗传变异是否会导致其表达水平的差异，并调节其在植入的人工装置上定殖的能力。数据显示，来自同一克隆复合体（CC）的分离株在编码表面黏附素的基因调控区域含有特定的SNP模式。因此，每个克隆谱系都显示出表面蛋白表达的特定谱型。用最常见的CCs的代表性分离株进行的共感染实验表明，在小鼠感染模型中，一些谱系在植入的导管上定殖的能力更强，这与在含有血浆蛋白的包被表面形成生物膜的能力更强相关。总之，结果表明表面黏附素表达水平的差异可能调节菌株引起PJI的倾向。鉴于葡萄球菌表面蛋白的高度保守性，我们的工作为研究基因间调控区域的多样化如何影响在医用植入物表面定殖的能力奠定了框架。
