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Tuberculosis (Edinb). 2006 Nov;86(6):445-60. Epub 2005 Dec 20.

ICAT-based comparative proteomic analysis of non-replicating persistent Mycobacterium tuberculosis.

Author information

1
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St, Chicago, IL 60612, USA. jkcn01@uic.edu <jkcn01@uic.edu>

Abstract

The non-replicating persistence (NRP) phenotype of Mycobacterium tuberculosis (NRP-TB) is assumed to be responsible for the maintenance of latent infection and the requirement of a long treatment duration for active tuberculosis. Isotope coded affinity tag-based proteomic analysis was used for the determination of the relative expression of large numbers of M. tuberculosis proteins during oxygen self-depletion under controlled conditions in a multi-chambered fermentor. Expression of the alpha-crystallin homolog protein, acr, was monitored and quantified to confirm entry into NRP. Relative expression of 586 and 628 proteins was determined in log phase vs. early stage NRP (NRP-1) and log phase vs. later stage NRP (NRP-2), respectively. Relative to expression in log phase and using an abundance ratio of +/-2.0 as a cutoff, 6.5% and 20.4% of proteins were found to be upregulated in NRP-1 and NRP-2, respectively while 20.3% and 13.4% were downregulated, respectively. Functional profiling revealed that 42.1%/39.8% of upregulated proteins and 41.2%/45.2% of downregulated proteins in NRP-1/NRP-2, respectively, were involved in small molecule metabolism. Among those proteins the highest proportions of 37.5% in NRP-1 were involved with degradation and of 45.1% in NRP-2 with energy metabolism. These results suggest distinct protein expression profiles in NRP-1 and NRP-2.

PMID:
16376151
DOI:
10.1016/j.tube.2005.10.002
[Indexed for MEDLINE]

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