title: In vivo transcriptional profiling of Yersinia pestis reveals a novel bacterial mediator of pulmonary inflammation.
abstract: Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. Very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. In this work, we analyzed the in vivo transcription kinetics of 288 bacterial open reading frames previously shown by microarray analysis to be dynamically regulated in the lung. Using this approach combined with bacterial genetics, we were able to identify five Y. pestis genes that contribute to the development of pneumonic plague. Deletion of one of these genes, ybtX, did not alter bacterial survival but attenuated host inflammatory responses during late-stage disease. Deletion of ybtX in another lethal respiratory pathogen, Klebsiella pneumoniae, also resulted in diminished host inflammation during infection. Thus, our in vivo transcriptional screen has identified an important inflammatory mediator that is common to two Gram-negative bacterial pathogens that cause severe pneumonia.
  
  
  OBJECTIVE
  Yersinia pestis is responsible for at least three major pandemics, most notably the Black Death of the Middle Ages. Due to its pandemic potential, ease of dissemination by aerosolization, and a history of its weaponization, Y. pestis is categorized by the Centers for Disease Control and Prevention as a tier 1 select agent most likely to be used as a biological weapon. To date, there is no licensed vaccine against Y. pestis. Importantly, an early "silent" phase followed by the rapid onset of nondescript influenza-like symptoms makes timely treatment of pneumonic plague difficult. A more detailed understanding of the bacterial and host factors that contribute to pathogenesis is essential to understanding the progression of pneumonic plague and developing or enhancing treatment options.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Pechous
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Broberg
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Nikolas M
authors.initials: NM
authors.lastname: Stasulli
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Miller
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina goldman@med.unc.edu.
authors.forename: William E
authors.identifier: http://orcid.org/0000-0002-1551-6718
authors.initials: WE
authors.lastname: Goldman
mesh_terms: D017353:Gene Deletion; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D010930:Plague / Q000382:microbiology / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D037521:Virulence Factors