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Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.

ABSTRACT: Recent advances in liquid chromatography and mass spectrometry have enabled the highly parallel, quantitative measurement of metabolites within a cell and the ability to trace their biochemical fates. In Mycobacterium tuberculosis (Mtb), these advances have highlighted major gaps in our understanding of central carbon metabolism (CCM) that have prompted fresh interpretations of the composition and structure of its metabolic pathways and the phenotypes of Mtb strains in which CCM genes have been deleted. High-throughput screens have demonstrated that small chemical compounds can selectively inhibit some enzymes of Mtb's CCM while sparing homologs in the host. Mtb's CCM has thus emerged as a frontier for both fundamental and translational research.

SUBMITTER: Rhee KY

PROVIDER: S-EPMC3601588 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.

Rhee Kyu Y KY de Carvalho Luiz Pedro Sorio LP Bryk Ruslana R Ehrt Sabine S Marrero Joeli J Park Sae Woong SW Schnappinger Dirk D Venugopal Aditya A Nathan Carl C

Trends in microbiology 20110510 7

Recent advances in liquid chromatography and mass spectrometry have enabled the highly parallel, quantitative measurement of metabolites within a cell and the ability to trace their biochemical fates. In Mycobacterium tuberculosis (Mtb), these advances have highlighted major gaps in our understanding of central carbon metabolism (CCM) that have prompted fresh interpretations of the composition and structure of its metabolic pathways and the phenotypes of Mtb strains in which CCM genes have been ...[more]

PMID: 21561773

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Project description:ObjectiveRecent guidelines recommend the use by healthcare personnel of a fit-tested N95 particulate respirator or higher-grade respiratory precaution in a patient undergoing bronchoscopy when pulmonary tuberculosis (PTB) is suspected. However, PTB may be unexpectedly diagnosed in this setting and therefore not evaluated, resulting in the unexpected exposure to Mycobacterium tuberculosis (MTB) of healthcare workers in the bronchoscopy suite. Here, we examined the incidence of unexpected exposure to MTB during flexible bronchoscopy and determined the exposure-related factors.MethodsBetween 2011 and 2013, a retrospective study was conducted to evaluate unexpected diagnoses of PTB in the bronchoscopy suite. During the study period, 1650 consecutive patients for whom previous CT scans were available and who underwent bronchoscopy for respiratory disease other than PTB were included. The results of bronchial washing, bronchoalveolar lavage, and post-bronchoscopic sputum were reviewed.ResultsPTB was unexpectedly diagnosed in 76 patients (4.6%). The presence of anthracofibrosis [odds ratio (OR), 3.878; 95% confidence interval (CI), 1.291-11.650; P = 0.016), bronchiectasis (OR, 1.974; 95% CI, 1.095-3.557; P = 0.024), or atelectasis (OR, 1.740; 95% CI, 1.010-2.903; P = 0.046) as seen on chest CT scan was independently associated with unexpected PTB. Patients with both anthracofibrosis and atelectasis were at much higher risk of unexpected PTB (OR, 4.606; 95% CI, 1.383-15.342; P = 0.013).ConclusionsThe risk of MTB exposure by healthcare personnel in the bronchoscopy suite due to patients with undiagnosed PTB has been underestimated. Therefore, in geographic regions with an intermediate PTB prevalence, such as South Korea (97/100,000 persons per year), higher-grade respiratory precaution, such as a fit-tested N95 particulate respirator, should be considered to prevent occupational exposure to MTB during routine bronchoscopy, especially in patients with CT-confirmed anthracofibrosis, bronchiectasis, or atelectasis.

Dataset Information

Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.

Publications

Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.

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