Pathogen-derived biomarkers for active tuberculosis diagnosis

Tucci, Paula; González‐Sapienza, Gualberto; Marı́n, Mónica

doi:10.3389/fmicb.2014.00549

Cited by 40 publications

(35 citation statements)

References 52 publications

(57 reference statements)

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“…Accurate diagnosis and effective treatment is essential for TB control. Sputum bacteriological tests, such as mycobacterial culture and smear microscopy, are still the most commonly used diagnostic methods for TB 2. However, the sensitivity of these tests is limited, and obtaining results from mycobacterial culture takes several weeks 1 3.…”

Section: Introductionmentioning

confidence: 99%

Double staining of bacilli and antigen Ag85B improves the accuracy of the pathological diagnosis of pulmonary tuberculosis

Che

Zhang

et al. 2015

J Clin Pathol

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Section: Introductionmentioning

confidence: 99%

Double staining of bacilli and antigen Ag85B improves the accuracy of the pathological diagnosis of pulmonary tuberculosis

Che

Zhang

et al. 2015

J Clin Pathol

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“…These results indicated that the M. tuberculosis H37Rv CFP preparation provides a good representation of the secreted/shed proteins because many main proteins of MTB were identified, with minimal contamination of non-MTB proteins (only a few peptides of human keratin were detected). Proteins highly recognized by anti-CFP antibodies (HspX, EsxB and Secreted antigen 85-a FbpA (Rv3804c)) are relevant pathogen antigens [33,44], recognized as secreted proteins by others [8,13], and evaluated as pathogen-derived biomarkers for active tuberculosis diagnosis [9].…”

Section: Resultsmentioning

confidence: 99%

“…Finally, considering the need of pathogen-derived biomarker validation for M. tuberculosis active diagnosis, we looked in the list of CFP for principal protein antigens detected in clinical samples [9], confirming the presence of 11 out of 12. Moreover, these putative biomarkers exhibited on average a high NSAF, being 10 of them in the P90% subgroup: GroEL2 (Rv0440), EsxA (Rv3875), HspX (Rv2031c), FbpA (Rv3804c), FbpB (Rv1886c), Mpt64 (Rv1980c), PstS1 (Rv0934), GlcB (Rv1837c), Apa (Rv1860) and FbpC (Rv0129c).…”

Section: Resultsmentioning

confidence: 99%

“…Membrane and exported proteins are crucial players for maintenance and survival of bacterial organisms in infected hosts, and their contribution to pathogenesis and immunological responses make these proteins relevant targets for medical research [11]. Consistently, various of the proteins identified in M. tuberculosis CFP were proposed as relevant mycobacterial virulence factors [64], putative active infection biomarkers [9] or vaccine candidates [60,65]. This shotgun proteomic approach allowed a deep comprehension of M. tuberculosis H37Rv culture filtrate proteins reporting proteomic evidence in this sub-fraction for 1314 proteins.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, it has been extensively used to identify pathogen biomarkers of M. tuberculosis infection and disease. These are generally major components identified by electrophoresis and mass spectrometry both in total extracts and culture filtrates [7–9].…”

Section: Introductionmentioning

confidence: 99%

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Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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21 Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium 22 tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted 23 and cell wall proteins interact with the host and play important roles in pathogenicity. These 24 proteins have been explored as candidate diagnostic markers, potential drug targets or vaccine 25 antigens, and special attention has been given to the role of their post-translational 26 modifications. With the purpose of contributing to the proteomic characterization of this 27 important pathogen including an O-glycosylation profile analysis, we performed a shotgun 28 analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass 29 spectrometry and a label-free spectral counting normalization approach for protein 30 quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the 31 most abundant proteins belong to the extracellular region or cell wall compartment, and that 32 the functional categories with higher protein abundance factor were virulence, detoxification 33 and adaptation, and cell wall and cell processes. In culture filtrate, 140 proteins were predicted 34 to contain one of the three types of bacterial N-terminal signal peptides. Besides, various 35 proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the 36 type VII secretion system using nonclassical secretion signals, were also identified. O-37 glycosylation was identified as a frequent modification, being present in 108 proteins, principally 38 lipoproteins and secreted immunogenic antigens. We could identify a group of proteins 39 consistently detected in previous studies, most of which were highly abundant proteins. 40 Interestingly, we also provide proteomic evidence for 62 novel O-glycosylated proteins, aiding 41 to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. 48 HIV-positive people [1]. Although TB diagnosis and successful treatment averts millions of 49 deaths each year, there are still large and persistent gaps related to this infection that must be 50 resolved in order to accelerate progress towards the goal of ending the TB epidemic endorsed 51 by WHO [1]. 52 M. tuberculosis (MTB), has evolved successful mechanisms to circumvent the hostile 53 environment of the macrophage, such as inhibiting the phagosome-lysosome fusion and to 54 escape the acidic environment inside the phagolysosome [2]. MTB may be unique in its ability 55 to exploit adaptive immune responses, through inflammatory lung tissue damage, to promote 56 its transmission [3]. It has been proposed that this microorganism was pressed by an 57 evolutionary selection that resulted in an infection that induces partial immunity, where the 58 host survives a long period after being infected with the pathogen, aiding in microorganism 59 persistence and transmission [3]. MTB mechanisms of evasion of host immune system were 60 proposed to have c...

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