Structural and functional studies of virulence factors in Mycobacterium tuberculosis infection

Structural and functional studies of virulence factors in Mycobacterium tuberculosis infection
Contact person: Rita Berisio, rita.berisio

unina.it

Description ▼

Tuberculosis is one of the main causes of infectious disease mortality in the world. The interaction between M. tuberculosis (MTB) and the human host after infection, often starting in the lungs, may manifest itself as a chronic disease or as a latent (or dormant) infection, a state capable to evade host responses. The probability of reactivation from dormancy is strongly affected by the type of host immune response and it is significantly enhanced in immuno-compromised patients. We have determined the first crystal structures of a Resuscitation Promoting Factors. These studies have provided insights into the mechanism of bacterial revival. M. tuberculosis is also able to invade and replicate within extra-pulmonary cell types, like epithelial cells. Adherence of the tubercle bacillus to epithelial cells is mediated by the heparin-binding hemagglutinin adhesin (HBHA), a 199-residue surface-exposed protein. The adherence of the bacterium mediated by HBHA relies on the interaction of its C-terminus (composed of lysine-rich motifs) with heparan sulfate-containing proteoglycans on the surface of epithelial cells. HBHA is also responsible for bacterial hemagglutination, a process which is essential to MTB infection. A thorough biochemical characterisation of HBHA has provided experimental evidence of a coiled coil nature of HBHA. These data, together with the low resolution structure of both a full-length and a truncated form of HBHA by Small Angle X-ray Scattering have unambiguously indicated that HBHA has a dimeric structure with an elongated shape. Our data provide insights into the twofold role of HBHA both for adhesion of M. tuberculosis to host epithelial cells and as an agglutination factor

Actors ▼

EmiliaMaria Pedone, empedone

unina.it
Rita Berisio, rita.berisio

unina.it

Keywords ▼

Tuberculosis, protein structure,

1. Calvanese, L., Falcigno, L., Maglione, C., Marasco, D., Ruggiero, A., Squeglia, F., Berisio, R. & D'Auria, G. (2013). Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis. Biopolymers. In the press.

2. Cantisani, M., Falanga, A., Incoronato, N., Russo, L., De Simone, A., Morelli, G., Berisio, R., Galdiero, M. & Galdiero, S. (2013). Conformational Modifications of gB from Herpes Simplex Virus Type 1 Analyzed by Synthetic Peptides. Journal of medicinal chemistry.

3. Correale, S., Ruggiero, A., Capparelli, R., Pedone, E. & Berisio, R. (2013). Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis. Acta crystallographica. Section D, Biological crystallography 69, 1697-706.

4. Squeglia, F., Bachert, B., Romano, M., Lukomski, S. & Berisio, R. (2013). Crystallization and preliminary X-ray crystallographic analysis of the variable domain of Scl2.3, a streptococcal collagen-like protein from invasive M3-type Streptococcus pyogenes. Acta crystallographica. Section F, Structural biology and crystallization communications 69, 1023-5.

5. Squeglia, F., Romano, M., Ruggiero, A., Vitagliano, L., De Simone, A. & Berisio, R. (2013). Carbohydrate recognition by RpfB from Mycobacterium tuberculosis unveiled by crystallographic and molecular dynamics analyses. Biophysical journal 104, 2530-9.

6. Correale, S., Ruggiero, A., Pedone, E. & Berisio, R. (2013). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis. Acta crystallographica. Section F, Structural biology and crystallization communications 69, 253-6.

7. Berisio, R. (2012). Editorial: learning from pathogens: exploiting host-pathogen liaison for therapeutic development. Current protein & peptide science 13, 697-8.

8. Berisio, R. & Vitagliano, L. (2012). Polyproline and triple helix motifs in host-pathogen recognition. Current protein & peptide science 13, 855-65.

9. Ruggiero, A., De Simone, P., Smaldone, G., Squeglia, F. & Berisio, R. (2012). Bacterial cell division regulation by Ser/Thr kinases: a structural perspective. Current protein & peptide science 13, 756-66.

10. Ruggiero, A., Marchant, J., Squeglia, F., Makarov, V., De Simone, A. & Berisio, R. (2013). Molecular determinants of inactivation of the resuscitation promoting factor B from Mycobacterium tuberculosis. Journal of biomolecular structure & dynamics 31, 195-205.

11. Berisio, R., Ciccarelli, L., Squeglia, F., De Simone, A. & Vitagliano, L. (2012). Structural and dynamic properties of incomplete immunoglobulin-like fold domains. Protein and peptide letters 19, 1045-53.

12. Berisio, R. (2012). Editorial: cell processes in bacterial diseases. Protein and peptide letters 19, 1011-2.

13. Di Maro, A., Berisio, R., Ruggiero, A., Tamburino, R., Severino, V., Zacchia, E. & Parente, A. (2012). Structural and enzymatic properties of an in vivo proteolytic form of PD-S2, type 1 ribosome-inactivating protein from seeds of Phytolacca dioica L. Biochemical and biophysical research communications 421, 514-20.

4. Ruggiero, A., Smaldone, G., Squeglia, F. & Berisio, R. (2012). Enhanced crystallizability by protein engineering approaches: a general overview. Protein and peptide letters 19, 732-42.

15. Esposito, C., Cantisani, M., D'Auria, G., Falcigno, L., Pedone, E., Galdiero, S. & Berisio, R. (2012). Mapping key interactions in the dimerization process of HBHA from Mycobacterium tuberculosis, insights into bacterial agglutination. FEBS letters 586, 659-67.

16. Squeglia, F., Marchetti, R., Ruggiero, A., Lanzetta, R., Marasco, D., Dworkin, J., Petoukhov, M., Molinaro, A., Berisio, R. & Silipo, A. (2011). Chemical basis of peptidoglycan discrimination by PrkC, a key kinase involved in bacterial resuscitation from dormancy. Journal of the American Chemical Society 133, 20676-9.

17. Ruggiero, A., Dattelbaum, J. D., Pennacchio, A., Iozzino, L., Staiano, M., Luchansky, M. S., Der, B. S., Berisio, R., D'Auria, S. & Vitagliano, L. (2011). Crystallization and preliminary X-ray crystallographic analysis of ligand-free and arginine-bound forms of Thermotoga maritima arginine-binding protein. Acta crystallographica. Section F, Structural biology and crystallization communications 67, 1462-5.

18. Esposito, C., Marasco, D., Delogu, G., Pedone, E. & Berisio, R. (2011). Heparin-binding hemagglutinin HBHA from Mycobacterium tuberculosis affects actin polymerisation. Biochemical and biophysical research communications 410, 339-44.

19. Vitagliano, L., Berisio, R. & De Simone, A. (2011). Role of hydration in collagen recognition by bacterial adhesins. Biophysical journal 100, 2253-61.

20. Ruggiero, A., Squeglia, F., Marasco, D., Marchetti, R., Molinaro, A. & Berisio, R. (2011). X-ray structural studies of the entire extracellular region of the serine/threonine kinase PrkC from Staphylococcus aureus. The Biochemical journal 435, 33-41.

21. Ruggiero, A., Squeglia, F., Pirone, L., Correale, S. & Berisio, R. (2011). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of a major fragment of the resuscitation-promoting factor RpfB from Mycobacterium tuberculosis. Acta crystallographica. Section F, Structural biology and crystallization communications 67, 164-8.

22. D'Auria, G., Esposito, C., Falcigno, L., Calvanese, L., Iaccarino, E., Ruggiero, A., Pedone, C., Pedone, E. & Berisio, R. (2010). Dynamical properties of cold shock protein A from Mycobacterium tuberculosis. Biochemical and biophysical research communications 402, 693-8.

23. Ruggiero, A., Marasco, D., Squeglia, F., Soldini, S., Pedone, E., Pedone, C. & Berisio, R. (2010). Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation. Structure 18, 1184-90.

24. Ruggiero, A., Squeglia, F., Izzo, V., Silipo, A., Vitagliano, L., Molinaro, A. & Berisio, R. (2010). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the peptidoglycan binding region of the Ser/Thr kinase PrkC from Staphylococcus aureus. Protein and peptide letters 17, 1296-9.

25. Esposito, C., Carullo, P., Pedone, E., Graziano, G., Del Vecchio, P. & Berisio, R. (2010). Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: implications for bacterial agglutination. FEBS letters 584, 1091-6.

26. Severino, V., Chambery, A., Di Maro, A., Marasco, D., Ruggiero, A., Berisio, R., Giansanti, F., Ippoliti, R. & Parente, A. (2010). The role of the glycan moiety on the structure-function relationships of PD-L1, type 1 ribosome-inactivating protein from P. dioica leaves. Molecular bioSystems 6, 570-9.

27. Ruggiero, A., Squeglia, F., Esposito, C., Marasco, D., Pedone, E., Pedone, C. & Berisio, R. (2010). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the resuscitation promoting factor interacting protein RipA from M. tuberculosis. Protein and peptide letters 17, 70-3.

28. Okuyama, K., Bachinger, H. P., Mizuno, K., Boudko, S., Engel, J., Berisio, R. & Vitagliano, L. (2009). Re: Microfibrillar structure of type I collagen in situ. Acta crystallographica. Section D, Biological crystallography 65, 1007-8; author reply 1009-10.

29. Ruggiero, A., Di Maro, A., Severino, V., Chambery, A. & Berisio, R. (2009). Crystal structure of PD-L1, a ribosome inactivating protein from Phytolacca dioica L. leaves with the property to induce DNA cleavage. Biopolymers 91, 1135-42.

30. Wekselman, I., Davidovich, C., Agmon, I., Zimmerman, E., Rozenberg, H., Bashan, A., Berisio, R. & Yonath, A. (2009). Ribosome's mode of function: myths, facts and recent results. Journal of peptide science : an official publication of the European Peptide Society 15, 122-30.

31. Berisio, R., De Simone, A., Ruggiero, A., Improta, R. & Vitagliano, L. (2009). Role of side chains in collagen triple helix stabilization and partner recognition. Journal of peptide science : an official publication of the European Peptide Society 15, 131-40.

32. Vitagliano, L., Ruggiero, A., Pedone, C. & Berisio, R. (2009). Molecular dynamics studies of the P pilus rod subunit PapA. Journal of peptide science : an official publication of the European Peptide Society 15, 192-9.

33. Ruggiero, A., Tizzano, B., Pedone, E., Pedone, C., Wilmanns, M. & Berisio, R. (2009). Crystal structure of the resuscitation-promoting factor (DeltaDUF)RpfB from M. tuberculosis. Journal of molecular biology 385, 153-62.

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* Structure and dynamics of the multi-domain resuscitation promoting factor RpfB from Mycobacterium tuberculosis (23 views)
Ruggiero A, Squeglia F, Romanò MF, Vitagliano L, De Simone A, Berisio R
J Biomol Struct Dyn (ISSN: 1538-0254electronic, 0739-1102linking), 2016 Sep; N/D: 1-9.

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* NMR Structure and Dynamics of the Resuscitation Promoting Factor RpfC Catalytic Domain (68 views)
Maione V, Ruggiero A, Russo L, De Simone A, Pedone PV, Malgieri G, Berisio R, Isernia C
Plos One (ISSN: 1932-6203electronic, 1932-6203linking), 2015 Nov 17; 10(11): e0142807-e0142807.

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* Structure and function of RNase AS, a polyadenylate-specific exoribonuclease affecting mycobacterial virulence in vivo (57 views)
Romanò MF, Van De Weerd R, Brouwer FCC, Roviello GN, Lacroix R, Sparrius M, Van Den Brink-van Stempvoort G, Maaskant JJ, Van Der Sar AM, Appelmelk BJ, Geurtsen JJ, Berisio R
Structurestructure (ISSN: 0969-2126, 1878-4186), 2014 May 6; 22(5): 719-730.

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* Expression, purification, crystallization and preliminary X-ray crystallographic analysis of a major fragment of the resuscitation-promoting factor RpfB from Mycobacterium tuberculosis (44 views)
Ruggiero A, Squeglia F, Pirone L, Correale S, Berisio R
Communicationsacta Crystallographica Section F Structural Biology And Crystallization (ISSN: 1744-3091, 1744-4309), 2011 Jan 1; 67(1): 164-168.

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* Dynamical properties of cold shock protein A from Mycobacterium tuberculosis (50 views)
D'Auria G, Esposito C, Falcigno L, Calvanese L, Iaccarino E, Ruggiero A, Pedone C, Pedone E, Berisio R
Biochem Biophys Res Commun (ISSN: 0006-291x, 1090-2104, 1090-2104electronic), 2010 Nov 26; 402(4): 693-698.

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5 Records (5 excluding Abstracts and Conferences).
Total impact factor: 16.474 (16.474 excluding Abstracts and Conferences).
Total 5-year impact factor: 15.49 (15.49 excluding Abstracts and Conferences).

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