AUTHOR=Wang Zhouhan , Xu Hao , Gu Beiqing , Jin Yanqi , Wang Tianyuan , Ma Jindi , Lu Yingfeng , Yu Xiaopeng , Zheng Beiwen , Zhang Yimin 

TITLE=Flavorubredoxin, a Candidate Trigger Related to Thrombotic Thrombocytopenic Purpura: Screening of the Complete Genome of a Salmonella enterica Serovar Typhimurium Isolate From an AIDS Case

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.864087

DOI=10.3389/fcimb.2022.864087

ISSN=2235-2988

ABSTRACT=<p>Thrombotic thrombocytopenic purpura (TTP) is one of the two classic thrombotic microangiopathy (TMA) diseases which could be induced by infections. To the best of our knowledge, this is the first report of an acquired immunodeficiency syndrome (AIDS) patient with acquired TTP induced by infection with <italic>Salmonella enterica</italic> serovar Typhimurium (hereafter, <italic>S</italic>. Typhimurium) isolate, <italic>S</italic>. Typhimurium_zhang, which was confirmed by serology and genetic taxonomy. The literature review identified 17 TMA-related genes encoding the candidate triggers, which were searched in the annotated genome sequence of <italic>S</italic>. Typhimurium_zhang. Anaerobic nitric oxide reductase flavorubredoxin (FlRd), encoded by <italic>norV</italic> which is related to another TMA, haemolytic uraemic syndrome (HUS), was found in <italic>S</italic>. Typhimurium_zhang. Basic local alignment search tool (BLAST) analysis revealed that <italic>norV</italic> and FlRd in <italic>S</italic>. Typhimurium_zhang, as well as eight <italic>S</italic>. Typhimurium type strains, have high identity with HUS-related <italic>Escherichia coli</italic> O157:H7 strain TW14359. Similar results were obtained from the BLAST analysis of 73 <italic>S</italic>. <italic>enterica</italic> isolates for congenital TTP which was also previously reported to be triggered by <italic>S</italic>. <italic>enterica</italic>. Phylogenetic analysis and amino acid sequence alignment revealed that FlRd was functional and highly conservative on 69 Enterobacteriaceae, including <italic>S</italic>. Typimurium_zhang and TW14359. In brief, we found <italic>norV</italic> in the genome of a <italic>S</italic>. Typhimurium clinical isolate that induced TTP in an AIDS patient. FlRd, the protein encoded by <italic>norV</italic>, probably triggered the TTP and was highly conservative, functional, and widespread in <italic>S</italic>. <italic>enterica</italic> and Enterobacteriaceae. More <italic>in vitro</italic> and <italic>in vivo</italic> studies are required to confirm our findings and determine the underlying mechanism.</p>