Gomes Ana Érika Inácio, Pacheco Thaisy, Dos Santos Cristiane da Silva, Pereira José Aires, Ribeiro Marcelo Lima, Darrieux Michelle, Ferraz Lúcio Fábio Caldas
Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Bragança Paulista, Brazil.
Laboratório de Biologia Molecular e Celular de Tumores, Universidade São Francisco, Bragança Paulista, Brazil.
Front Microbiol. 2021 Jan 21;11:601921. doi: 10.3389/fmicb.2020.601921. eCollection 2020.
Although originally known as an opportunistic pathogen, has been considered a worldwide health threat nowadays due to the emergence of hypervirulent and antibiotic-resistant strains capable of causing severe infections not only on immunocompromised patients but also on healthy individuals. Fimbriae is an essential virulence factor for , especially in urinary tract infections (UTIs), because it allows the pathogen to adhere and invade urothelial cells and to form biofilms on biotic and abiotic surfaces. The importance of fimbriae for pathogenicity is highlighted by the large number of fimbrial gene clusters on the bacterium genome, which requires a coordinated and finely adjusted system to control the synthesis of these structures. In this work, we describe KpfR as a new transcriptional repressor of fimbrial expression in and discuss its role in the bacterium pathogenicity. with disrupted gene exhibited a hyperfimbriated phenotype with enhanced biofilm formation and greater adhesion to and replication within epithelial host cells. Nonetheless, the mutant strain was attenuated for colonization of the bladder in a murine model of urinary tract infection. These results indicate that KpfR is an important transcriptional repressor that, by negatively controlling the expression of fimbriae, prevents from having a hyperfimbriated phenotype and from being recognized and eliminated by the host immune system.
虽然最初被认为是一种机会性病原体，但由于出现了高毒力和抗生素耐药菌株，如今已被视为全球健康威胁，这些菌株不仅能在免疫功能低下的患者中引起严重感染，也能在健康个体中引发感染。菌毛是该病原体的一种重要毒力因子，特别是在尿路感染（UTIs）中，因为它能使病原体黏附并侵入尿道上皮细胞，并在生物和非生物表面形成生物膜。细菌基因组上大量的菌毛基因簇突出了菌毛对该病原体致病性的重要性，这需要一个协调且精细调节的系统来控制这些结构的合成。在这项研究中，我们将KpfR描述为该病原体菌毛表达的一种新的转录抑制因子，并讨论其在细菌致病性中的作用。基因被破坏的该病原体表现出过度菌毛化的表型，生物膜形成增强，对上皮宿主细胞的黏附及在其中的复制能力更强。尽管如此，在尿路感染的小鼠模型中，该突变菌株在膀胱定植方面的能力减弱。这些结果表明，KpfR是一种重要的转录抑制因子，通过负向控制菌毛的表达，防止该病原体出现过度菌毛化表型，避免被宿主免疫系统识别和清除。
