Mycobacterium tuberculosis PPE protein Rv0256c induces strong B cell response in tuberculosis patients

Abraham, Philip; Latha, G Suman; Valluri, Vijaya Lakshmi; Mukhopadhyay, Sangita

doi:10.1016/j.meegid.2013.06.023

Cited by 19 publications

(14 citation statements)

References 33 publications

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“…We reported earlier that PPE2 is expressed during active pathogenesis of M. tuberculosis 28. Our studies indicate that PPE2 contains a physiologically active NLS as well as a DNA-binding leucine zipper motif that translocates into host cell nucleus and inhibits gene transcription driven by the inos promoter and promotes better survival of M. smegmatis expressing PPE2 in vitro as well as in vivo (Figs 1, 2, 4, 5 and 7; Fig.…”

Section: Discussionmentioning

confidence: 57%

“…The PPE2 open reading frame was amplified from a bacterial artificial chromosome (BAC) clone BAC-Rv329 (A5), a kind gift from Dr. Shekhar C. Mande, NCCS, Pune, India using a forward primer (5′-CGAGATCTATGACCGCCCCGATCTGGAT-3′) and a reverse primer (5′-GCGAATTCTCACTCCACCCGGGTCGCTGA-3′) appended with BglII and EcoRI sites (underlined) as described earlier28. The amplicon was cloned into the BglII and EcoR1 site of a mammalian expression vector pEGFP-C1 (Clontech, Palo Alto, CA, USA) in frame with the EGFP protein.…”

Section: Methodsmentioning

confidence: 99%

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The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

Bhat

Srivastava

Kotturu

et al. 2017

Sci Rep

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Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal. PPE2 was translocated into the macrophage nucleus via the classical importin α/β pathway where it interacted with a GATA-binding site overlapping with the TATA box of inos promoter and inhibited NO production. PPE2 prolonged intracellular survival of a surrogate bacterium M. smegmatis in vitro as well as in vivo. This information are likely to improve our knowledge of host-pathogen interactions during M. tuberculosis infection which is crucial for designing effective anti-TB therapeutics.

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Section: Discussionmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

Bhat

Srivastava

Kotturu

et al. 2017

Sci Rep

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“…tuberculosis PE/PPE proteins, several studies have been undertaken to identify suitable antigens that could be used to discriminate BCG-vaccinated healthy individuals from active TB patients [12,15,18,21,22]. We demonstrated earlier that the PPE17 protein could be used as a potent B-cell as well as T-cell marker to detect active TB disease [15].…”

Section: Discussionmentioning

confidence: 99%

“…We reported earlier that PPE17 could discriminate patients with active TB from BCG-vaccinated healthy individuals [15,22]. Interestingly, we observed that PPE17 displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases than early secreted antigenic target 6 protein (ESAT-6) and purified protein derivative (PPD) as well as other PPE proteins [14–18,21,22]. We also demonstrated that PPE17 is a potent T-cell antigen which elicited stronger gamma interferon response as compared to PPD [15].…”

Section: Introductionmentioning

confidence: 99%

The N-terminal domain of Mycobacterium tuberculosis PPE17 (Rv1168c) protein plays a dominant role in inducing antibody responses in active TB patients

Abraham¹,

Pathak²,

Pradhan³

et al. 2017

PLoS ONE

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The PPE (proline-proline-glutamic acid) proteins of Mycobacterium tuberculosis are characterized by a conserved N-terminal domain of approximately 180 amino acids and variable C-terminal domain. Since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (TB) as they act as a source of antigenic variation. We have demonstrated earlier that one of the PPE proteins PPE17 (Rv1168c) induces strong B-cell and T-cell responses in active TB disease and also displays a higher antibody titer compared to immunodominant antigens such as ESAT-6, Hsp60 and PPD. However, the immunodominant domain of PPE17 (N-terminal or C-terminal) was not examined in detail. In the present study, we observed that antibody responses elicited in TB patients were directed mostly towards the N-terminal domain of PPE17 (N-PPE17). The antibody generated against N-PPE17 in TB patients did not significantly cross-react with N-terminal domains of other PPE proteins used in this study. Our data suggest that the N-terminal domain of PPE17 protein is immunodominant and could be used as a better serodiagnostic marker than the full-length PPE17 protein.

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“…Several PE/PPE proteins on account of being surface exposed and containing repetitive sequences can serve as targets for the humoral immune system. Indeed, several PE/PPE family members have been shown to induce strong antibody responses , examples include Rv0160c or PE4 ; the PE25/PPE41 protein complex ; Rv1169c, Rv0978c, and Rv1818c ; Rv2608 ; PPE44 ; Rv2430c ; Rv0256c ; and Rv1168c or PPE17 . The expression of PE/PPE members has often been found to vary, and seroreactivity against them can help to differentiate between different clinical categories of patients with TB like pulmonary, extrapulmonary, smear‐negative, or relapsed .…”

Section: Pe/ppe Proteins and Anti‐tb Vaccine And Drug Designmentioning

confidence: 99%

Immunoregulatory functions and expression patterns of PE/PPE family members: Roles in pathogenicity and impact on anti‐tuberculosis vaccine and drug design

2015

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The Mycobacterium tuberculosis genome was sequenced more than 15 years ago. It revealed a lot of interesting information, one of which was that 10% of the total coding capacity of the M. tuberculosis genome is dedicated to the PE/PPE family. There is a gradual expansion of these proteins from nonpathogenic to pathogenic mycobacteria, and there is increasing evidence that PE/PPE proteins play important roles in mycobacterial pathogenesis. In this review, we discuss PE/ PPE proteins, their close functional association with the ESX clusters, their immunomodulatory functions, and their important roles in mycobacterial virulence. In addition, we have attempted to review and compile information available in the literature detailing the expression patterns of PE/PPE family members in different mycobacterial species and also during infection. Our attempt has been to provide a succinct overview of this interesting family.

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Mycobacterium tuberculosis PPE protein Rv0256c induces strong B cell response in tuberculosis patients

Cited by 19 publications

References 33 publications

The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

The N-terminal domain of Mycobacterium tuberculosis PPE17 (Rv1168c) protein plays a dominant role in inducing antibody responses in active TB patients

Immunoregulatory functions and expression patterns of PE/PPE family members: Roles in pathogenicity and impact on anti‐tuberculosis vaccine and drug design

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