title: Involvement of the post-transcriptional regulator Hfq in Yersinia pestis virulence.
abstract: BACKGROUND
  Yersinia pestis is the causative agent of plague, which is transmitted primarily between fleas and mammals and is spread to humans through the bite of an infected flea or contact with afflicted animals. Hfq is proposed to be a global post-transcriptional regulator that acts by mediating interactions between many regulatory small RNAs (sRNAs) and their mRNA targets. Sequence comparisons revealed that Y. pestis appears to produce a functional homologue of E. coli Hfq.
  
  
  RESULTS
  Phenotype comparisons using in vitro assays demonstrated that Y. pestis Hfq was involved in resistance to H(2)O(2), heat and polymyxin B and contributed to growth under nutrient-limiting conditions. The role of Hfq in Y. pestis virulence was also assessed using macrophage and mouse infection models, and the gene expression affected by Hfq was determined using microarray-based transcriptome and real time PCR analysis. The macrophage infection assay showed that the Y. pestis hfq deletion strain did not have any significant difference in its ability to associate with J774A.1 macrophage cells. However, hfq deletion appeared to significantly impair the ability of Y. pestis to resist phagocytosis and survive within macrophages at the initial stage of infection. Furthermore, the hfq deletion strain was highly attenuated in mice after subcutaneous or intravenous injection. Transcriptome analysis supported the results concerning the attenuated phenotype of the hfq mutant and showed that the deletion of the hfq gene resulted in significant alterations in mRNA abundance of 243 genes in more than 13 functional classes, about 23% of which are known or hypothesized to be involved in stress resistance and virulence.
  
  
  CONCLUSIONS
  Our results indicate that Hfq is a key regulator involved in Y. pestis stress resistance, intracellular survival and pathogenesis. It appears that Hfq acts by controlling the expression of many virulence- and stress-associated genes, probably in conjunction with small noncoding RNAs.
authors: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors: Jing
authors: J
authors: Geng
authors: Yajun
authors: Y
authors: Song
authors: Lei
authors: L
authors: Yang
authors: Yanyan
authors: Y
authors: Feng
authors: Yefeng
authors: Y
authors: Qiu
authors: Gang
authors: G
authors: Li
authors: Jingyu
authors: J
authors: Guo
authors: Yujing
authors: Y
authors: Bi
authors: Yi
authors: Y
authors: Qu
authors: Wang
authors: W
authors: Wang
authors: Xiaoyi
authors: X
authors: Wang
authors: Zhaobiao
authors: Z
authors: Guo
authors: Ruifu
authors: R
authors: Yang
authors: Yanping
authors: Y
authors: Han
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D002460:Cell Line; D004352:Drug Resistance, Microbial; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D010587:Phagocytosis; D011112:Polymyxin B / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D014774:Virulence / Q000502:physiology*; D015010:Yersinia pestis / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D011112:Polymyxin B