Exploitation of Mycobacterium tuberculosis Reporter Strains to Probe the Impact of Vaccination at Sites of Infection

Details

• Alternative Title:
  PLoS Pathog
• Personal Author:
  Sukumar, Neelima ; Tan, Shumin ; Aldridge, Bree B. ; Russell, David G.
• Description:
  Mycobacterium tuberculosis (Mtb) remains a major public health problem, with an effective vaccine continuing to prove elusive. Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment. Here, we utilize reporter Mtb strains that respond to specific host immune stresses such as hypoxia and nitric oxide (hspX'::GFP), and phagosomal maturation (rv2390c'::GFP), to investigate vaccine-induced alterations in the environmental niche during experimental murine infections. While vaccination undoubtedly decreased bacterial burden, we found that it also appeared to accelerate Mtb's adoption of a phenotype better equipped to survive in its host. We subsequently utilized a novel replication reporter strain of Mtb to demonstrate that, in addition to these alterations in host stress response, there is a decreased percentage of actively replicating Mtb in vaccinated hosts. This observation was supported by the differential sensitivity of recovered bacteria to the front-line drug isoniazid. Our study documents the natural history of the impact that vaccination has on Mtb's physiology and replication and highlights the value of reporter Mtb strains for probing heterogeneous Mtb populations in the context of a complex, whole animal model.
• Subjects:
  Animals Antitubercular Agents Fluorescent Antibody Technique Genes, Reporter Host-Pathogen Interactions Hypoxia Isoniazid Lung Macrophages Mice Mice, Inbred C57BL Mycobacterium Tuberculosis Nitric Oxide Tuberculosis Tuberculosis Vaccines Vaccination

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• Source:
  PLoS Pathog. 2014; 10(9).
• Pubmed ID:
  25233380
• Pubmed Central ID:
  PMC4169503
• Document Type:
  Journal Article
• Funding:
  1DP2LM011952-01/DP/NCCDPHP CDC HHS/United States ; AI067027/AI/NIAID NIH HHS/United States ; DP2 LM011952/LM/NLM NIH HHS/United States ; HL055936/HL/NHLBI NIH HHS/United States ; R01 AI067027/AI/NIAID NIH HHS/United States ; R01 HL055936/HL/NHLBI NIH HHS/United States
• Volume:
  10
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a0fd88598442d1e97694f9b4aa5087879310c61381eb7e94a8669f1aa12c9117
• Download URL:
  https://stacks.cdc.gov/view/cdc/32271/cdc_32271_DS1.pdf
• File Type:
  [PDF - 5.52 MB ]