Molecular mimicry between HSP 65 of Mycobacterium leprae and cytokeratin 10 of the host keratin; Role in pathogenesis of leprosy

Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Bisht, Deepa; Sharma, Prashant; Sharma, Bhawna; Gupta, Umesh Datta; Sengupta, Utpal

doi:10.1016/j.cellimm.2012.06.011

Cited by 19 publications

(26 citation statements)

References 36 publications

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“…HSP65 is another such example of the major immune targets in leprosy and tuberculosis. Singh et al [37] reported evidence for the existence of molecular mimicry between M. leprae HSP65 and cytokeratin-10 of keratin (host protein) and established the role of this HSP in the pathogenesis of leprosy by clinical manifestation. 18-kDa antigen (HSP18) of M. leprae also plays an important role in the survival of M. leprae pathogen in host cells.…”

Section: Resultsmentioning

confidence: 99%

A S52P mutation in the ‘α‐crystallin domain’ of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function

et al. 2013

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Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major immunodominant antigen of M. leprae pathogen. Previously, we have reported the existence of two M. leprae HSP18 variants in various leprotic patients. One of the variants has serine at position 52, whereas the other one has proline at the same position. We have also reported that HSP18 having proline at position 52 ( HSP18P 52 ) is a nonameric protein and exhibits chaperone function. However, the structural and functional characterization of wild-type HSP18 having serine at position 52 ( HSP18S 52 ) is yet to be explored. Furthermore, the implications of the S52P mutation on the structure and chaperone function of HSP18 are not well understood. Therefore, we cloned and purified these two HSP18 variants. We found that HSP18S 52 is also a molecular chaperone and an oligomeric protein. Intrinsic tryptophan fluorescence and far-UV CD measurements revealed that the S52P mutation altered the tertiary and secondary structure of HSP18. This point mutation also reduced the oligomeric assembly and decreased the surface hydrophobicity of HSP18, as revealed by HPLC and 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid binding studies, respectively. Mutant protein was less stable against thermal and chemical denaturation and was more susceptible towards tryptic cleavage than wild-type HSP18. HSP18P 52 had lower chaperone function and was less effective in protecting thermal killing of Escherichia coli than HSP18S 52. Taken together, our data suggest that serine 52 is important for the larger oligomerization and chaperone function of HSP18. Because both variants differ in stability and function, they may have different roles in the survival of M. leprae in infected hosts. Abbreviations ACD, a-crystallin domain; bis-ANS, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid, dipotassium salt; CFU, colony-forming unit; FRET, F€ orster resonance energy transfer; Gu-HCl, guanidine hydrochloride; IPTG, isopropyl thio-b-D-galactoside; MDH, malate dehydrogenase; sHSP, small heat shock protein. Structured digital abstract

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Section: Resultsmentioning

confidence: 99%

A S52P mutation in the ‘α‐crystallin domain’ of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function

et al. 2013

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“…Mice of the control (n ¼ 10) and experimental (n ¼ 15) group were hyperimmunized with saline and 25 mg of protein concentration of MLSA emulsion respectively as previously described [8].…”

Section: Mlsa-hyperimmunized Micementioning

confidence: 99%

“…Estimation of auto-antibodies against myelin basic protein by ELISA 2.6.1. Human sera ELISA was performed by using the protocol with some modifications as described earlier [8]. Briefly, each well of microtitre plates (Nunc, Denmark) was coated with 5 mg/ml of MBP (Sigma, USA) for 18 h at 4 C. Wells were blocked with 3% BSA (Sigma, USA) in PBS for 1 h. Serum (1:100) was added in duplicate wells followed by incubation at 37 C for 2 h. After 3 washings, 1:10,000 diluted anti-human IgG peroxidase conjugated (Sigma, USA) was added into each well.…”

Section: Protocol For Transfer Of Auto-reaction By Adoptive Transfermentioning

confidence: 99%

“…Lymphocyte proliferation assay was done with some modifications as described earlier [8]. Cultures were set in triplicate with or without 20 mg/ml MBP in culture medium into 96 well flat bottom culture plates (Nunc, Denmark) and incubated for 5 days in a humidified CO 2 incubator (Forma Scientific Inc, USA) at 37 C with 5% CO 2 in air.…”

Section: Effect Of Mbp On Lymphocyte Proliferation Of Leprosy Patientmentioning

confidence: 99%

“…Earlier, it was reported that MBP is one of the constituents in the circulating immune complexes (CIC) of lepromatous leprosy (LL) patients and was suggested that MBP released after nerve damage caused by M. leprae was responsible for production of anti-MBP antibodies, which further may lead to demyelination and nerve damage [7]. Molecular mimicry may be the underlying mechanism for production of autoantibodies and might be responsible for pathological destruction in leprosy [8,9]. Molecular mimicry is defined as immunological cross-reactivity between infectious agent and host antigenic determinant/s [10].…”

Section: Introductionmentioning

confidence: 99%

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