Molecular Signatures Related to the Virulence of Bacillus cereus Sensu Lato, a Leading Cause of Devastating Endophthalmitis

mSystems

Wei-Hua Chen¹  Jiao Shao²  Bian-Jin Sun²  Yu-Yu Li²  Zheng-Bo Xue²  Mei-Qin Zheng²  Die Zhang²  Yi Xu²  Jian-Zhong Su²  Dan-Dan Fan²  Jian Yuan²  Clara Pak³  Kai Li⁴  Yong-Liang Lou⁵ 

[1] Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China;School of Ophthalmology and Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China;University of Rochester Medical Center, Rochester, New York, USA;Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China;Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China;

关键词: endophthalmitis;    Bacillus;    pangenome;    virulence;    evolution;   

DOI  :  10.1128/mSystems.00745-19

来源: DOAJ

【 摘 要 】

ABSTRACT Bacillus endophthalmitis is a devastating eye infection that causes rapid blindness through extracellular tissue-destructive exotoxins. Despite its importance, knowledge of the phylogenetic relationships and population structure of intraocular Bacillus spp. is lacking. In this study, we sequenced the whole genomes of eight Bacillus intraocular pathogens independently isolated from 8/52 patients with posttraumatic Bacillus endophthalmitis infections in the Eye Hospital of Wenzhou Medical University between January 2010 and December 2018. Phylogenetic analysis revealed that the pathogenic intraocular isolates belonged to Bacillus cereus, Bacillus thuringiensis and Bacillus toyonensis. To determine the virulence of the ocular isolates, three representative strains were injected into mouse models, and severe endophthalmitis leading to blindness was observed. Through incorporating publicly available genomes for Bacillus spp., we found that the intraocular pathogens could be isolated independently but displayed a similar genetic context. In addition, our data provide genome-wide support for intraocular and gastrointestinal sources of Bacillus spp. belonging to different lineages. Importantly, we identified five molecular signatures of virulence and motility genes associated with intraocular infection, namely, plcA-2, InhA-3, InhA-4, hblA-5, and fliD using pangenome-wide association studies. The characterization of overrepresented genes in the intraocular isolates holds value to predict bacterial evolution and for the design of future intervention strategies in patients with endophthalmitis. IMPORTANCE In this study, we provided a detailed and comprehensive clinicopathological and pathogenic report of Bacillus endophthalmitis over the 8 years of the study period. We first reported the whole-genome sequence of Bacillus spp. causing devastating endophthalmitis and found that Bacillus toyonensis is able to cause endophthalmitis. Finally, we revealed significant endophthalmitis-associated virulence genes involved in hemolysis, immunity inhibition, and pathogenesis. Overall, as more sequencing data sets become available, these data will facilitate comparative research and will reveal the emergence of pathogenic “ocular bacteria.”

【 授权许可】

Unknown