Conde-Pérez Kelly, Vázquez-Ucha Juan C, Álvarez-Fraga Laura, Ageitos Lucía, Rumbo-Feal Soraya, Martínez-Guitián Marta, Trigo-Tasende Noelia, Rodríguez Jaime, Bou Germán, Jiménez Carlos, Beceiro Alejandro, Poza Margarita
Servicio de Microbiología del Complejo Hospitalario Universitario de A Coruña (CHUAC), Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain.
Microbiome and Health, Faculty of Science, University of A Coruña, A Coruña, Spain.
Front Microbiol. 2021 Oct 5;12:752070. doi: 10.3389/fmicb.2021.752070. eCollection 2021.
is a multidrug-resistant pathogen that represents a serious threat to global health. possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes , , , and showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene , coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔΔ double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of , , , , and in the pathogenicity of and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.
是一种多重耐药病原体，对全球健康构成严重威胁。具有多种毒力因子，这些毒力因子有助于细菌的致病性。其中，铁载体杆菌铁载体是最重要的毒力因子之一，对感染的发展至关重要。在本研究中，我们对菌株ATCC 17978中的杆菌铁载体基因簇进行了深入分析。为此，构建了19个单基因同基因突变株，并进行了进一步的表型分析。缺乏生物合成基因、、、和的单个突变体由于杆菌铁载体产生的中断而显示出毒力的显著丧失。同样，编码杆菌铁载体受体的基因也被发现对细菌致病作用至关重要。此外，对ΔΔ双突变株的分析表明，铁载体之间存在高水平的基因冗余，其中杆菌铁载体基因簇的特定基因的作用可以由其菌毛铁载体冗余基因来完成。总体而言，本研究突出了、、、、和在的致病性中的重要作用，并为设计针对这种微生物的新型抗毒力药物提供了潜在的治疗靶点。
