Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and under in vitro conditions affecting aerobic respiration
Proceedings of the National Academy of Sciences of the United States of America, Volume 102, No. 43, Year 2005
Notification
URL copied to clipboard!
Description
Transcription profiling of genes encoding components of the respiratory chain and the ATP synthesizing apparatus of Mycobacterium tuberculosis was conducted in vivo in the infected mouse lung, and in vitro in bacterial cultures subjected to gradual oxygen depletion and to nitric oxide treatment. Transcript levels changed dramatically as infection progressed from bacterial exponential multiplication (acute infection) to cessation of bacterial growth (chronic infection) in response to host immunity. The proton-pumping type-I NADH dehydrogenase and the aa3-type cytochrome c oxidase were strongly down-regulated. Concurrently, the less energy-efficient cytochrome bd oxidase was transiently up-regulated. The nitrate transporter NarK2 was also up-regulated, indicative of increased nitrate respiration. The reduced efficiency of the respiratory chain was accompanied by decreased expression of ATP synthesis genes. Thus, adaptation of M. tuberculosis to host immunity involves three successive respiratory states leading to decreased energy production. Decreased bacterial counts in mice infected with a cydC mutant (defective in the cytochrome bd oxidase-associated transporter) at the transition to chronic infection provided initial evidence that the bd oxidase pathway is required for M. tuberculosis adaptation to host immunity. In vitro, NO treatment and hypoxia caused a switch from transcription of type I to type II NADH dehydrogenase. Moreover, cytochrome bd oxidase expression increased, but cytochrome c oxidase expression decreased slightly (nitric oxide) or not at all (hypoxia). These specific differences in respiratory metabolism during M. tuberculosis growth arrest in vitro and in vivo will guide manipulation of in vitro conditions to model bacterial adaptation to host immunity. © 2005 by The National Academy of Sciences of the USA.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1255738/bin/pnas_0507850102_index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC1255738/bin/pnas_0507850102_07850Fig6.jpg
Authors & Co-Authors
Shi, Lanbo
United States, Newark
Public Health Research Institute
Sohaskey, Charles D.
United States, Long Beach
Va Long Beach Healthcare System
Kana, Bavesh Davandra
South Africa, Johannesburg
University of the Witwatersrand
Dawes, Stephanie S.
South Africa, Johannesburg
University of the Witwatersrand
North, Robert J.
United States, Saranac Lake
Trudeau Institute
Mizrahi, Valerie
South Africa, Johannesburg
University of the Witwatersrand
Gennaro, Maria Laura
United States, Newark
Public Health Research Institute
Statistics
Citations: 280
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1073/pnas.0507850102
ISSN:
00278424