Differential Culturability of Mycobacterium tuberculosis in Culture-Negative Sputum of Patients With Pulmonary Tuberculosis and in a Simulated Model of Dormancy

Tuberculosis (TB) remains a leading killer among infectious diseases of humans worldwide. Delayed diagnosis is a crucial problem in global TB control programs. Bacteriological methods currently used to diagnose TB in endemic countries take up to 8 weeks, which poses a significant delay in starting a...

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Bibliographic Details
Published in:	Frontiers in microbiology Vol. 10; p. 2381
Main Authors:	Dusthackeer, Azger, Balasubramanian, Magizhaveni, Shanmugam, Govindarajan, Priya, Shanmuga, Nirmal, Christy Rosaline, Sam Ebenezer, Rajadas, Balasubramanian, Angayarkanni, Mondal, Rajesh Kumar, Thiruvenkadam, Kannan, Hemanth Kumar, A. K., Ramachandran, Geetha, Subbian, Selvakumar
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 23-10-2019
Subjects:	bacteriological diagnosis clinical isolate organism Microbiology Mycobacteirum tuberculosis resuscitation sputum samples tuberculosis
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Summary:	Tuberculosis (TB) remains a leading killer among infectious diseases of humans worldwide. Delayed diagnosis is a crucial problem in global TB control programs. Bacteriological methods currently used to diagnose TB in endemic countries take up to 8 weeks, which poses a significant delay in starting antibiotic therapy. The presence of a heterogeneous population of Mycobacterium tuberculosis , the causative agent of TB, is among the reasons for delayed diagnosis by bacteriological methods. Previously, it has been shown that mycobacterial resuscitation-promoting factors (RPFs), a family of proteins secreted by actively growing bacteria into the media, are capable of activating the growth of dormant bacteria, thus enhancing the detection of bacilli in the sputum of confirmed TB cases. However, the variability in bacterial resuscitation by RPF in the sputum of suspected pulmonary TB cases that showed differential smear and/or culture positivity during diagnosis has not been fully explored. Here, we report the presence of non-replicating bacteria in the sputum of suspected TB cases that show differential growth response to RPF treatment. Using crude and recombinant RPF treatment, we show improved sensitivity and reduced time to detect bacilli in the sputum samples of smear-positive/culture-negative or smear-negative/culture-negative cases. We also report the phenotypic heterogeneity in the RPF responsiveness among Mtb strains using an in vitro dormancy model. Our findings have implications for improving the bacteriological diagnostic modalities currently used to diagnose TB in endemic countries.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Jann-Yuan Wang, National Taiwan University Hospital, Taiwan; Willy Ssengooba, Makerere University, Uganda; Margarita Shleeva, A N Bach Institute of Biochemistry (RAS), Russia Edited by: Aleksandra Barac, University of Belgrade, Serbia This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology
ISSN:	1664-302X 1664-302X
DOI:	10.3389/fmicb.2019.02381