Abstract
Rapid and accurate differentiation of Mycobacterium tuberculosis complex (MTBC) species from other mycobacterium is essential for appropriate therapeutic management, timely intervention for infection control and initiation of appropriate health care measures. However, routine clinical characterization methods for Mycobacterium tuberculosis (Mtb) species remain both, time consuming and labor intensive. In the present study, an innovative liquid Chromatography-Mass Spectrometry method for the identification of clinically most relevant Mycobacterium tuberculosis complex species is tested using a model set of mycobacterium strains. The methodology is based on protein profiling of Mycobacterium tuberculosis complex isolates, which are used as markers of differentiation. To test the resolving power, speed, and accuracy of the method, four ATCC type strains and 37 recent clinical isolates of closely related species were analyzed using this new approach. Using different deconvolution algorithms, we detected hundreds of individual protein masses, with a subpopulation of these functioning as species-specific markers. This assay identified 216, 260, 222, and 201 proteoforms for M. tuberculosis ATCC 27294™, M. microti ATCC 19422™, M. africanum ATCC 25420™, and M. bovis ATCC 19210™ respectively. All clinical strains were identified to the correct species with a mean of 95% accuracy. Our study successfully demonstrates applicability of this novel mass spectrometric approach to identify clinically relevant Mycobacterium tuberculosis complex species that are very closely related and difficult to differentiate with currently existing methods. Here, we present the first proof-of-principle study employing a fast mass spectrometry-based method to identify the clinically most prevalent species within the Mycobacterium tuberculosis species complex.
Highlights
Mycobacterium tuberculosis is responsible for one of the most devastating and chronic infectious diseases known to science and is an important and formidable human pathogen that has claimed nearly 1.2 million lives in 2019 (Andersen and Brennan, 1994)
To verify whether different Mycobacterium tuberculosis complex (MTBC) species show unique MS spectrum profiles, the masses of the deconvoluted proteoforms from each species were aligned to construct a list of consensus markers
We evaluated whether the MS spectrum profile and common proteoforms obtained from different species within MTBC can differentiate the species within the complex
Summary
Mycobacterium tuberculosis is responsible for one of the most devastating and chronic infectious diseases known to science and is an important and formidable human pathogen that has claimed nearly 1.2 million lives in 2019 (Andersen and Brennan, 1994). 10 million people were infected in 2019 and the pathogen can persist in a hidden form if undiagnosed for a long period of time within the human host (Bloom and Murray, 1992; WHO, 2020). Almost 10% of an infected population will progress to disease (active tuberculosis) following a latent period (from weeks to decades) (Bloom and Murray, 1992). Multidrug-resistant tuberculosis has recently emerged (MDR-TB) and represents an enormous challenge to the public health system worldwide. Worldwide in 2019, close to half a million people developed rifampicin-resistant TB (RR-TB), of which 78% had multidrug-resistant TB (MDR-TB). The largest increase seen globally in the number of nontuberculosis mycobacterial (NTM) and MTBC infections was observed in patients who had already contracted the human immunodeficiency virus (HIV)
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