PNEUMOCOCCAL SURFACE PROTEIN A
Gene Name - PspA
Cell Location - Cell wall - PspA is bound to the cell wall via phosphoryl-choline moiety [1]. PspA is attached to the surface of the pneumococcus by the C-terminal end of the molecule [2]. The N-terminal half of the molecule is thought to be surface exposed as all protective monoclonal antibodies reactive to PspA on the pneumococcal cell surface bind it [3].
FUNCTION
Present in all pneumococcal isolates regardless of serotype, PspA has been proven to play a key role in the virulence of Streptococcus pneumoniae. It is a human lactoferrin-binding protein which inhibits complement deposition on the surface of pneumococci [4] [3]. It plays a role in cellular metabolic processes and immune evasion in the body [5]. The presence of PspA in pneumococci is also known to delay/slow down the clearance of the bacteria from the blood stream. PspA also aids in colonisation by adhering to epithelial cell membranes [6].
STRUCTURE
Click on the image for more information on the secondary and tertiary structure of pneumococcal surface protein A.
PROTEIN SEQUENCE
10 20 30 40 50
MNKKKMILTS LASVAILGAG FVTSSPTFVR AEEAPVASQS KAEKDYDAAK
60 70 80 90 100
KDAKNAKKAV EDAQKALDDA KAAQKKYDED QKKTEKKAAA VKKIDEEHQA
110 120 130 140 150
ANLKSQQALV EFLAAQREGN PKKKKAAQAK LEEAEKAEKE KKKEFDKAQA
160 170 180 190 200
VVVPEATELA ETKKKADEAK VKEPELTKKL EEAKAKSEEA EKKATEAKQK
210 220 230 240 250
VDAEHAKEVV PQAKIAELEN EVQKLEKDLK EIDESDSEDY VKEGLRAPLQ
260 270 280 290 300
SELDAKQAKL SKLEELSDKI DELDAEIAKL EKNVEDFKNS NGEQAEQYRA
310 320 330 340 350
AAEEDLAAKQ AELEKTEADL KKAVNEPEKP APAPETPAPE APAEQPKPAP
360 370 380 390 400
APQPAPAPKP EKPAEQPKAE KTDDQQAEED YARRSEEEYN RLTQQQPPKA
410 420 430 440 450
EKPAPAPKPE QPAPAPKIGW KQENGMWYFY NTDGSMATGW LQNNGSWYYL
460 470 480 490 500
NANGSMVTGW LQNNGSWYYL NANGSMATGW LQNNGSWYYL NANGAMATGW
510 520 530 540 550
LQNNDSWYYL NASGAMATGW AKVNGSWYYL NANGAMATGW LQYNGSWYYL
560 570 580 590 600
NANGAMATGW VKVNGSWYYL NANGSMATGW VKDGDTWYYL EASGAMKASQ
610 620 630
WFKVSDKWYY VNGLGALAVN TTVDGYKVNA NGEWV
SEQUENCE LENGTH - 635
CURRENT FIELD STATUS

CURRENT TRIAL STATUS
Phase I [1] [7]​
​
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Clinical trials in adults.
-
Immunisation of mice with human sera [8].
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Humans immunised orally with Salmonella expressing PspA [9].
-
Humans immunised with recombinant PspA [10].

IMMUNE RESPONSE GENERATED
-
It is hypothesised that PspA will be able to protect against many diverse strains of Streptococcus pneumoniae due to its location in all known strains [11].
-
Recombinant PspA proteins elicit capabilities of inducing a protective mechanism against S. pneumonia in different animal models and against different serotypes [10].
-
Immunoglobulin G (IgG) antibodies were observed to be the leading serum antibody to PspA, with peak antibody response by the host occurring in childhood.
-
Immunoglobulin M (IgM) antibodies showed comparable levels of IgM antibodies to those of IgG in children, however, IgG antibodies levels are significantly higher to IgM levels in adults.
-
The number of Immunoglobulin A (IgA) antibody-secreting cells are proven to be less than both IgG and IgM, with levels of IgA staying low after immunisation for the first 2 years of life [12].
-
PspA immunisation has been shown to protect against otherwise fatal sepsis caused by pneumococci when the hosts (mice) are challenged with a dose of >105 times the 50% lethal dose and pneumococci was cleared from the hosts bloodstream [8] [11].
-
A phase I trial with recombinant PspA showed the protein to be immunogenic in humans [10].

MECHANISM OF VIRULENCE
-
Choline-binding protein, plays relevant physiological role in virulence.
-
Delays/slows down the ability for the host to clear the blood of pneumococci.
-
Interferes with the antiphagocytic properties of Streptococcus pneumoniae [11].
-
Inhibits complement deposition on the bacterial surface.
-
The presence of PspA makes the killing of pneumococci by apolactoferrin much less effective, when PspA is absent it can be observed that apolactoferrin acts as a great tool to killing pneumococci and when present these capabilities are diminished [13].
-
A possible mechanism of virulence of PspA is also the ionic interactions between the positively charged amino acid Lysine which is found in PspA and the negatively charged polysaccharide layer. These interactions can act as a mechanism to stabilise the capsule and increase virulence [11].
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