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
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

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].

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].

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].
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