Costa Maiana de Oliveira Cerqueira E, do Nascimento Ana Paula Barbosa, Martins Yasmmin Cortes, Dos Santos Marcelo Trindade, Figueiredo Agnes Marie de Sá, Perez-Rueda Ernesto, Nicolás Marisa Fabiana
Laboratório Nacional de Computação Científica (LNCC), Petrópolis, Brazil.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.
Front Microbiol. 2023 Jan 10;13:1049819. doi: 10.3389/fmicb.2022.1049819. eCollection 2022.
is one of the most prevalent and relevant pathogens responsible for a wide spectrum of hospital-associated or community-acquired infections. In addition, methicillin-resistant may display multidrug resistance profiles that complicate treatment and increase the mortality rate. The ability to produce biofilm, particularly in device-associated infections, promotes chronic and potentially more severe infections originating from the primary site. Understanding the complex mechanisms involved in planktonic and biofilm growth is critical to identifying regulatory connections and ways to overcome the global health problem of multidrug-resistant bacteria.
In this work, we apply literature-based and comparative genomics approaches to reconstruct the gene regulatory network of the high biofilm-producing strain Bmb9393, belonging to one of the highly disseminating successful clones, the Brazilian epidemic clone. To the best of our knowledge, we describe for the first time the topological properties and network motifs for the pathogen. We performed this analysis using the ST239-SCCIII Bmb9393 strain. In addition, we analyzed transcriptomes available in the literature to construct a set of genes differentially expressed in the biofilm, covering different stages of the biofilms and genetic backgrounds of the strains.
The Bmb9393 gene regulatory network comprises 1,803 regulatory interactions between 64 transcription factors and the non-redundant set of 1,151 target genes with the inclusion of 19 new regulons compared to the N315 transcriptional regulatory network published in 2011. In the Bmb9393 network, we found 54 feed-forward loop motifs, where the most prevalent were coherent type 2 and incoherent type 2. The non-redundant set of differentially expressed genes in the biofilm consisted of 1,794 genes with functional categories relevant for adaptation to the variable microenvironments established throughout the biofilm formation process. Finally, we mapped the set of genes with altered expression in the biofilm in the Bmb9393 gene regulatory network to depict how different growth modes can alter the regulatory systems. The data revealed 45 transcription factors and 876 shared target genes. Thus, the gene regulatory network model provided represents the most up-to-date model for , and the set of genes altered in the biofilm provides a global view of their influence on biofilm formation from distinct experimental perspectives and different strain backgrounds.
是引起广泛的医院相关感染或社区获得性感染的最普遍且重要的病原体之一。此外，耐甲氧西林的可能表现出多重耐药性特征，使治疗复杂化并增加死亡率。产生生物膜的能力，特别是在与装置相关的感染中，会引发源自原发部位的慢性且可能更严重的感染。了解浮游生物和生物膜生长所涉及的复杂机制对于确定调控联系以及克服多重耐药细菌这一全球健康问题的方法至关重要。
在这项工作中，我们应用基于文献和比较基因组学的方法来重建高生物膜产生菌株Bmb9393的基因调控网络，该菌株属于高度传播的成功克隆之一，即巴西流行克隆。据我们所知，我们首次描述了该病原体的拓扑特性和网络基序。我们使用ST239 - SCCIII Bmb9393菌株进行了此分析。此外，我们分析了文献中可用的转录组，以构建一组在生物膜中差异表达的基因，涵盖生物膜的不同阶段以及菌株的遗传背景。
与2011年发表的N315转录调控网络相比，Bmb9393基因调控网络包含64个转录因子与1151个非冗余靶基因之间的1803个调控相互作用，并包含19个新的调控子。在Bmb9393网络中，我们发现了54个前馈环基序，其中最普遍的是连贯型2和不连贯型2。生物膜中差异表达基因的非冗余集由1794个基因组成，其功能类别与适应生物膜形成过程中建立的可变微环境相关。最后，我们将Bmb9393基因调控网络中生物膜中表达改变的基因集进行映射，以描述不同生长模式如何改变调控系统。数据揭示了45个转录因子和876个共享靶基因。因此，所提供的基因调控网络模型代表了该病原体的最新模型，生物膜中表达改变的基因集从不同的实验视角和不同的菌株背景提供了它们对生物膜形成影响的全局视图。
