Whole genome sequencing and comparative analysis of novel pathogen elizbethkingia anophelis against oxidative stress
Date of Issue2017
School of Biological Sciences
Singapore Centre on Environmental Life Sciences Engineering
Elizabethkingia anophelis is an emerging pathogen that causes life-threatening infections in neonates, severely immunocompromised and postoperative patients with extremely high mortality. Multi-drug resistance, biofilm formation and oxidative stress resistance imply its pathogenesis. However, the lack of genomic information on E. anophelis hinders our understanding of its mechanisms of pathogenesis. In this study, we report the complete genome sequence of a clinically isolated E. anophelis NUHP1 strain, which is the first complete genome of the Elizabethkingia genus. E. anophelis NUHP1 has a circular genome of 4,369,828 base pairs and 4,141 predicted coding sequences. Sequence analysis and the genome comparison between E. anophelis NUHP1 and assemblies of E. anophelis isolated from mosquito gut indicates that E. anophelis has well-developed systems for scavenging iron and stress response. Many putative virulence factors and antibiotic resistance genes were identified, underscoring the potential host–pathogen interactions and antibiotic resistance. RNA-sequencing-based transcriptome profiling indicates that expressions of genes involved in synthesis of a yersiniabactin-like iron siderophore and heme utilization are highly induced as a protective mechanism toward oxidative stress caused by hydrogen peroxide treatment. Chromeazurol sulfonate assay verified that siderophore production of E. anophelis is increased in the presence of oxidative stress. Moreover, the transcriptome profiling comparison between E. anophelis NUHP1 treated with hydrogen peroxide and with mouse blood further showed that E. anophelis NUHP1 displayed the similar protective mechanism associated with iron siderophore and heme utilization when contact with mouse blood, indicating that oxidative stress is the major stress for E. anophelis NUHP1 when infect hosts and the strong resistance to oxidative stress enables E. anophelis to be dominant in the blood meal feeding mosquitoes. Furthermore, we also showed that hemoglobin but not ferric iron greatly facilitates the growth, hydrogen peroxide tolerance and biofilm formation of E. anophelis NUHP1. Our study suggests that siderophore production and heme uptake pathways might play essential roles in stress response and virulence of the emerging pathogen E. anophelis.