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PNEUMOCOCCAL SURFACE ADHESIN A

Gene Name - PsaA

Cell Location - PsaA is a sub-surface protein found beneath the cell wall and capsular layers that protrudes from and is attached directly to the lipid of the cytoplasmic membrane [1] [2]. 

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FUNCTION                                                                                                                                                                             

PsaA is a highly conserved substrate-binding lipoprotein found in all known strains of Streptococcus pneumoniae. It is known to play a role as a solute transporter. It is a part of an ATP binding cassette (ABC) type transport system for manganese. It binds to Mn2+ and is responsible for its transport.
It has also been proven to be responsible for the adherence of pneumococci as research has shown that PsaA mutants fail to bind tissue cultured alveolar cells and endothelial cells [1] [2] [3]. 

STRUCTURE                                                                                                                                                                           

litemol_screenshot psaa.png

Click on the image for more information on the secondary and tertiary structure of pneumococcal surface adhesin A.

PROTEIN SEQUENCE                                                                                                                                                       

10                         20                         30                         40                         50     
MKKLGTLLVL      FLSAIILVAC         ASGKKDTTSG    QKLKVVATNS     IIADITKNIA
60                         70                         80                         90                         100
GDKIDLHSIV       PIGQDPHEYE     PLPEDVKKTS      EADLIFYNGI       NLETGGNAWF
110                       120                       130                       140                       150
TKLVENAKKT     ENKDYFAVSD     GVDVIYLEGQ     NEKGKEDPHA    WLNLENGIIF
160                       170                       180                       190                       200    
AKNIAKQLSA     KDPNNKEFYE    KNLKEYTDKL      DKLDKESKDK     FNKIPAEKKL
210                       220                       230                       240                       250   
IVTSEGAFKY      FSKAYGVPSA      YIWEINTEEE       GTPEQIKTLV       EKLRQTKVPS
260                       270                       280                       290                       300      
LFVESSVDDR      PMKTVSQDTN   IPIYAQIFTD        SIAEQGKEGD     SYYSMMKYNL

DKIAEGLAK                                 

SEQUENCE LENGTH - 309

CURRENT FIELD STATUS

cdc-IFpQtennlj8-unsplash.jpg

CURRENT TRIAL STATUS

Phase I

  • PsaA expressed as an E. coli recombinant protein [1].

  • PsaA and PspA combination vaccine [4].

  • Immunisation in a murine model [5]. 

michael-longmire-L9EV3OogLh0-unsplash.jp

IMMUNE RESPONSE GENERATED

  • Recombinant PsaA has been shown to be safe for use in humans [1].

  • Mice immunised through non-oral means with purified PsaA, combined with strong adjuvants to enhances the response to the presence of PsaA, showed significant levels of protection against challenge with Streptococcus pneumoniae and greater survival times [3] [6].

  • The use of PsaA immunisation is highly effective against nasopharyngeal colonisation with the addition of the adjuvant cholera toxin B with PsaA greatly reduces levels of nasopharyngeal carriage [5] [6].

  • PsaA is immunogenic and naturally occurring nasopharyngeal colonisation provokes an increase in PsaA antibodies [1].

  • Elicits protection against invasive diseases and nasopharyngeal carriage. Combinations of PsaA with PspA show to further increase levels of protection from carriage [7].

cdc-ljiPMfg-0m0-unsplash.jpg

MECHANISM OF VIRULENCE

  • PsaA is a lipoprotein. Lipoproteins have been shown to modulate inflammatory processes and aid in the movement of other virulence factors into the cell [4] [8].   

  • Acts as a binding protein aiding in transport of Mn2+ [1] [8].

  • Functions as an adhesin which aids in the pneumococcal attachment to host cells [1].

  • Worsens pneumococcal colonisation and infection [1].

RELATED GENE BANKS                                                                                                                                                    

RELATED ARTICLES                                                                                                                                                            

[1]         G. Rajam, J. M. Anderton, G. M. Carlone, J. S. Sampson, and E. W. Ades, “Pneumococcal surface adhesin A (PsaA): A review,” Critical Reviews in Microbiology, vol. 34, no. 3–4. Crit Rev Microbiol, pp. 131–142, Aug. 2008, doi: 10.1080/10408410802275352.

 

[2]         J. W. Johnston, L. E. Myers, M. M. Ochs, W. H. Benjamin, D. E. Briles, and S. K. Hollingshead, “Lipoprotein PsaA in virulence of Streptococcus pneumoniae: Surface accessibility and role in protection from superoxide,” Infection and Immunity, vol. 72, no. 10, pp. 5858–5867, Oct. 2004, doi: 10.1128/IAI.72.10.5858-5867.2004.

 

[3]         S. S. Tai, “Streptococcus pneumoniae protein vaccine candidates: Properties, activities and animal studies,” Critical Reviews in Microbiology, vol. 32, no. 3. Crit Rev Microbiol, pp. 139–153, Sep. 01, 2006, doi: 10.1080/10408410600822942.

 

[4]         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.

 

[5]         D. E. Briles, J. C. Paton, R. Mukerji, E. Swiatlo, and M. J. Crain, “Pneumococcal Vaccines,” Microbiology Spectrum, vol. 7, no. 6, Nov. 2019, doi: 10.1128/microbiolspec.GPP3-0028-2018.

 

[6]         A. D. Ogunniyi, R. L. Folland, D. E. Briles, S. K. Hollingshead, and J. C. Paton, “Immunization of mice with combinations of pneumococcal virulence proteins elicits enhanced protection against challenge with Streptococcus pneumoniae,” Infection and Immunity, vol. 68, no. 5, pp. 3028–3033, May 2000, doi: 10.1128/IAI.68.5.3028-3033.2000.

 

[7]         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.

 

[8]         A. Kovacs-Simon, R. W. Titball, and S. L. Michell, “Lipoproteins of bacterial pathogens,” Infection and Immunity, vol. 79, no. 2. American Society for Microbiology (ASM), pp. 548–561, Feb. 2011, doi: 10.1128/IAI.00682-10.

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