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PNEUMOCOCCAL CHOLINE-BINDING PROTEIN A

Gene Name - PcpA

Cell Location - Cell wall -  Pneumococcal choline-binding protein A is bound to the cell wall via phosphoryl-choline moiety [1].

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FUNCTION                                                                                                                                                                             

PcpA plays a role in the protection against sepsis and lung infections [1]. Its expression in cells only occurs in places of low manganese concentrations, such as the lungs and blood, and areas of high concentrations lead to limited PcpA expression. Therefore, its expression is largely controlled by manganese-dependant regulators [2].
It also functions as an adhesin, whereby it aids in the adherence of Streptococcus pneumoniae to epithelial cells found in the nasopharynx and lungs [3]. 

STRUCTURE                                                                                                                                                                           

litemol_screenshot pcpa.png

Click on the image for more information on the secondary and tertiary structure of pneumococcal choline-binding protein A.

PROTEIN SEQUENCE                                                                                                                                                       

10                         20                         30                         40                         50     
MKKTTILSLT        TAAVILAAYV       PNEPILADTP      SSEVIKETKV        GSIIQQNNIK
60                         70                         80                         90                         100
YKVLTVEGNI       GTVQVGNGVT  PVEFEAGQDG   KPFTIPTKIT          VGDKVFTVTE
110                       120                       130                       140                       150
VASQAFSYYP      DETGRIVYYP      SSITIPSSIK           KIQKKGFHGS    KAKTIIFDKG
160                       170                       180                       190                       200      

SQLEKIEDRA      FDFSELEEIE        LPASLEYIGT        SAFSFSQKLK     KLTFSSSSKL
210                       220                       230                       240                       250      

ELISHEAFAN      LSNLEKLTLP        KSVKTLGSNL      FRLTTSLKHV       DVEEGNESFA
260                       270                       280                       290                       300    

SVDGVLFSKD     KTQLIYYPSQ      KNDESYKTPK     ETKELASYSF       NKNSYLKKLE
310                       320                       330                       340                       350
LNEGLEKIGT      FAFADAIKLE       EISLPNSLET        IERLAFYGNL      ELKELILPDN
360                       370                       380                       390                       400   

VKNFGKHVMN  GLPKLKSLTI         GNNINSLPSF     FLSGVLDSLK      EIHIKNKSTE
410                       420                       430                       440                       450      

FSVKKDTFAI       PETVKFYVTS       EHIKDVLKSN      LSTSNDIIVE        KVDNIKQETD
460                       470                       480                       490                       500
VAKPKKNSNQ    GVVGWVKDKG  LWYYLNESGS    MATGWVKDKG  LWYYLNESGS
510                       520                       530                       540                       550 

MATGWVKDKG  LWYYLNESGS    MATGWVKDKG  LWYYLNESGS     MATGWVKDKG
560                       570                       580                       590                       600
LWYYLNESGS     MATGWVKDKG LWYYLNESGS     MATGWVTVSG  KWYYTYNSGD
610                       620                                  
LLVNTTTPDG      YRVNANGEWV  G

SEQUENCE LENGTH - 621

CURRENT FIELD STATUS

cdc-IFpQtennlj8-unsplash.jpg

CURRENT TRIAL STATUS

Phase 1

  • Clinical trials of a PcpA vaccine [1].

  • Clinical trials of a PcpA vaccine combined with PhtD [1][4]. 

  • Immunisation with PcpA in murine model [2].

  • Immunisation of toddlers with PcpA PhtD, and PlyD1 [4].

michael-longmire-L9EV3OogLh0-unsplash.jp

IMMUNE RESPONSE GENERATED

  • PcpA has shown high levels of protection in preclinical studies against pneumonia and sepsis.

  • Mice immunised with PcpA through a sepsis and pneumonia models showed significantly lower levels of Streptococcus pneumonia cells and infection in their lungs than control mice. Immunisation also led to higher survival times in mice.

  • PcpA failed to show signs of protecting against colonisation and carriage [2].  

cdc-ljiPMfg-0m0-unsplash.jpg

MECHANISM OF VIRULENCE

  • Choline-binding protein which plays relevant physiological role in virulence [1].

RELATED GENE BANKS                                                                                                                                                    

RELATED ARTICLES                                                                                                                                                            

[1]         T. Lagousi, P. Basdeki, J. Routsias, and V. Spoulou, “Novel protein-based pneumococcal vaccines: Assessing the use of distinct protein fragments instead of full-length proteins as vaccine antigens,” Vaccines, vol. 7, no. 1. MDPI AG, 2019, doi: 10.3390/vaccines7010009.

 

[2]         D. T. Glover, S. K. Hollingshead, and D. E. Briles, “Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis,” Infection and Immunity, vol. 76, no. 6, pp. 2767–2776, Jun. 2008, doi: 10.1128/IAI.01126-07.

 

[3]         M. N. Khan, S. K. Sharma, L. M. Filkins, and M. E. Pichichero, “PcpA of Streptococcus pneumoniae mediates adherence to nasopharyngeal and lung epithelial cells and elicits functional antibodies in humans,” Microbes and Infection, vol. 14, no. 12, pp. 1102–1110, Oct. 2012, doi: 10.1016/j.micinf.2012.06.007.

 

[4]         K. Moffitt and R. Malley, “Rationale and prospects for novel pneumococcal vaccines,” Human Vaccines and Immunotherapeutics, vol. 12, no. 2, pp. 383–392, Feb. 2016, doi: 10.1080/21645515.2015.1087625.

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