PfbA (Plasmin(ogen) and Fibronectin Binding protein A) is an adhesin present on the surface of Streptococcus pneumoniae. Initial studies characterized PfbA as plasmin(ogen) and fibronectin binding protein and later it was found that it binds with many other proteins of the extracellular matrix such as fibrinogen, collagen and laminin. It also binds to blood protein human serum albumin (HSA). Interestingly, PfbA exhibits no binding with serum albumins of bovine (BSA), rabbit (RSA) and porcine (PSA) which are sequentially and structurally homologous to HSA. This suggests that PfbA is likely involved in host specificity. Therefore, to get more insights into this aspect, a detailed analysis, which includes the interaction of rPfbA with HSA/BSA/RSA/PSA at different pHs by bio-layer interferometry, comparison of sequences and surface electrostatic potential of HSA/BSA/RSA/PSA, lysine modification of HSA by succinylation and subsequent interaction analysis of succinylated HSA with rPfbA and the secondary structural content estimation by FT-IR spectroscopy was carried out. Since large protrusions are another important geometric feature of protein surfaces, the property was also analyzed for HSA/BSA/RSA/PSA. The results of the above studies clearly suggest that the rPfbA exhibits host specificity by selectively binding only to HSA and not with its homologous BSA/RSA/PSA. Since the three dimensional structures of these albumins are highly similar, it is likely that rPfbA utilizes the differences in the surface electrostatic charge in combination with surface protrusions of HSA/BSA/RSA/PSA for the selective molecular recognition process and this feature may be important in the pathogenesis of pneumococcal infection.
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KP gratefully acknowledges the Science and Engineering Research Board (SERB), Government of India for the financial support in the form of Grant (No. EMR/2016/000891). KP thanks DST-FIST, Government of India for the DLS and FT-IR equipments sanctioned to the department (No. SR/FST/LSII-037/2014 (C) dt. 29.03.2016). SS thanks SERB for the Fellowship.
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Conflict of interest
There is no conflict of interest among the authors.
This article does not contain any studies with human participants or animals performed by any of the authors.
Dave S, Carmicle S, Hammerschmidt S, Pangburn MK, McDaniel LS (2004) Dual roles of PspC, a surface protein of Streptococcus pneumoniae, in binding human secretory IgA and factor H. J Immunol 173(1):471–477PubMedCrossRefGoogle Scholar
Rosenow C, Ryan P, Weiser JN et al (1997) Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 25(5):8CrossRefGoogle Scholar
Hakansson A, Roche H, Mirza S, McDaniel LS, Brooks-Walter A, Briles DE (2001) Characterization of binding of human lactoferrin to pneumococcal surface protein A. Infect Immun 69(5):3372–3381PubMedPubMedCentralCrossRefGoogle Scholar
Morales M, Martin-Galiano AJ, Domenech M, Garcia E (2015) Insights into the evolutionary relationships of LytA autolysin and Ply pneumolysin-like genes in Streptococcus pneumoniae and related streptococci. Genome Biol Evol 7(9):2747–2761PubMedPubMedCentralCrossRefGoogle Scholar
Yamaguchi M, Goto K, Hirose Y et al (2019) Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae. Commun Biol 2(1):96PubMedPubMedCentralCrossRefGoogle Scholar
Papasergi S, Garibaldi M, Tuscano G et al (2010) Plasminogen- and fibronectin-binding protein B is involved in the adherence of Streptococcus pneumoniae to human epithelial cells. J Biol Chem 285(10):7517–7524PubMedPubMedCentralCrossRefGoogle Scholar
Yamaguchi M, Terao Y, Mori Y, Hamada S, Kawabata S (2008) PfbA, a novel plasmin- and fibronectin-binding protein of Streptococcus pneumoniae, contributes to fibronectin-dependent adhesion and antiphagocytosis. J Biol Chem 283(52):36272–36279PubMedPubMedCentralCrossRefGoogle Scholar
Yamaguchi M, Hirose Y, Takemura M, Ono M, Sumitomo T, Nakata M, Terao Y, Kawabata S (2019) Streptococcus pneumoniae evades host cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA. Front Cell Infect Microbiol 9:301PubMedPubMedCentralCrossRefGoogle Scholar
Frolet C, Beniazza M, Roux L, Gallet B, Noirclerc-Savoye M, Vernet T, Di Guilmi AM (2010) New adhesin functions of surface-exposed pneumococcal proteins. BMC Microbiol 10:190PubMedPubMedCentralCrossRefGoogle Scholar
Blanco LP, Payne BL, Feyertag F, Alvarez-Ponce D (2018) Proteins of generalist and specialist pathogens differ in their amino acid composition. Life Sci Alliance 1(4):e201800017PubMedPubMedCentralCrossRefGoogle Scholar
Hammerschmidt S, Tillig MP, Wolff S, Vaerman J-P, Chhatwal GS (2000) Species-specific binding of human secretory component to SpsA protein of Streptococcus pneumoniae via a hexapeptide motif. Mol Microbiol 36(3):726–736PubMedCrossRefGoogle Scholar
Agarwal V, Hammerschmidt S, Malm S, Bergmann S, Riesbeck K, Blom AM (2012) Enolase of Streptococcus pneumoniae binds human complement inhibitor C4b-binding protein and contributes to complement evasion. J Immunol 189(7):3575–3584PubMedCrossRefGoogle Scholar
Pickering AC, Vitry P, Prystopiuk V et al (2019) Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion. PLoS Pathog 15(6):e1007816PubMedPubMedCentralCrossRefGoogle Scholar
Beulin DSJ, Radhakrishnan D, Suresh SC et al (2017) Streptococcus pneumoniae surface protein PfbA is a versatile multidomain and multiligand-binding adhesin employing different binding mechanisms. FEBS J 284(20):3404–3421PubMedCrossRefGoogle Scholar
Cayot P, Tainturier G (1997) The quantification of protein amino groups by the trinitrobenzenesulfonic acid method: a reexamination. Anal Biochem 249(2):184–200PubMedCrossRefGoogle Scholar
Myhre EB, Kronvall G (1980) Demonstration of specific binding sites for human serum albumin in group C and G streptococci. Infect Immun 27(1):6–14PubMedPubMedCentralGoogle Scholar
Egesten A, Frick I-M, Morgelin M, Olin AI, Bjorck L (2011) Binding of albumin promotes bacterial survival at the epithelial surface. J Biol Chem 286(4):2469–2476PubMedCrossRefGoogle Scholar
Raghav A, Ahmad J, Alam K (2017) Nonenzymatic glycosylation of human serum albumin and its effect on antibodies profile in patients with diabetes mellitus. PLoS ONE 12(5):e0176970PubMedPubMedCentralCrossRefGoogle Scholar
Steinhardt J, Krijn J, Leidy JG (1971) Differences between bovine and human serum albumins: binding isotherms, optical rotatory dispersion, viscosity, hydrogen ion titration, and fluorescence effects. Biochemistry 10(22):4005–4015PubMedCrossRefGoogle Scholar
Ha J-S, Ha C-E, Chao J-T, Petersen CE, Theriault A, Bhagavan NV (2003) Human serum albumin and its structural variants mediate cholesterol efflux from cultured endothelial cells. Biochim Biophys Acta 1640(2–3):119–128PubMedCrossRefGoogle Scholar
Reichenwallner J, Oehmichen M-T, Schmelzer CEH, Hauenschild T, Kerth A, Hinderberger D (2018) Exploring the pH-induced functional phase space of human serum albumin by EPR spectroscopy. Magnetochemistry 4(4):47CrossRefGoogle Scholar
Tanford C, Buzzell JG (1956) The viscosity of aqueous solutions of bovine serum albumin between pH 4.3 and 10.5. J Phys Chem 60(2):225–231CrossRefGoogle Scholar
Böhme U, Scheler U (2007) Effective charge of bovine serum albumin determined by electrophoresis NMR. Chem Phys Lett 435(4):342–345CrossRefGoogle Scholar
Zhang Z, Tan M, Xie Z, Dai L, Chen Y, Zhao Y (2011) Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol 7(1):58–63PubMedCrossRefGoogle Scholar
Tayyab S, Haq SK, Sabeeha, Aziz MA, Khan MM, Muzammil S (1999) Effect of lysine modification on the conformation and indomethacin binding properties of human serum albumin. Int J Biol Macromol 26(2–3):173–180PubMedCrossRefGoogle Scholar
Ishtikhar M, Rabbani G, Khan S, Khan RH (2015) Biophysical investigation of thymoquinone binding to ‘N’ and ‘B’ isoforms of human serum albumin: exploring the interaction mechanism and radical scavenging activity. RSC Adv 5(24):18218–18232CrossRefGoogle Scholar
Yuan L, Liu M, Sun B et al (2017) Calorimetric and spectroscopic studies on the competitive behavior between (−)-epigallocatechin-3-gallate and 5-fluorouracil with human serum albumin. J Mol Liq 248:330–339CrossRefGoogle Scholar
Basu A, Bhayye S, Kundu S, Das A, Mukherjee A (2018) Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions. RSC Adv 8(54):30717–30724CrossRefGoogle Scholar
Huang YT, Liao HF, Wang SL, Lin SY (2016) Glycation and secondary conformational changes of human serum albumin: study of the FTIR spectroscopic curve-fitting technique. AIMS Biophys 3(2):247–260CrossRefGoogle Scholar
La D, Rodriguez JE, Venkatraman V, Li B, Sael L, Ueng S, Ahrendt S, Kihara D (2009) 3D-SURFER: software for high throughput protein surface comparison and analysis. Bioinformatics 25:2843–2844PubMedPubMedCentralCrossRefGoogle Scholar