HISTIDINE TRIAD PROTEIN D
Gene Name - PhtD
Cell Location - PhtD is a well conserved protein found on the surface of the cell wall of all strains of Streptococcus pneumonia. [1] [2].
FUNCTION
The roles of PhtD in S. pneumoniae are linked to surface binding and helping the pathogen evade the host immune response. It works to adhere pneumococci to the respiratory epithelial tissue and mucosal surfaces, thereby increasing the ability of pneumococcus to invade a host. It has also been shown to inhibit complement deposition thus decreasing the ability of antibodies to clear pathogens. [2] [3].
STRUCTURE
Click on the image for more information on the secondary and tertiary structure of Histidine triad protein D.
PROTEIN SEQUENCE
10 20 30 40 50
MKINKKYLAG SVAVLALSVC SYELGRHQAG QVKKESNRVS YIDGDQAGQK
60 70 80 90 100
AENLTPDEVS KREGINAEQI VIKITDQGYV TSHGDHYHYY NGKVPYDAII
110 120 130 140 150
SEELLMKDPN YQLKDSDIVN EIKGGYVIKV DGKYYVYLKD AAHADNIRTK
160 170 180 190 200
EEIKRQKQER SHNHNSRADN AVAAARAQGR YTTDDGYIFN ASDIIEDTGD
210 220 230 240 250
AYIVPHGDHY HYIPKSDLSA SELAAAQAYW NGKQGSRPSS SSSHNANPAQ
260 270 280 290 300
PRLSENHNLT VTPTYHQNQG ENISSLLREL YAKPLSERHV ESDGLIFDPA
310 320 330 340 350
QITSRTANGV AVPHGDHYHF IPYSQLSPLE EKLARIIPLR YRSNHWVPDS
360 370 380 390 400
RPEQPSPQST PEPSPSPQPA PNPQPAPSNP IDEKLVKEAV RKVGDGYVFE
410 420 430 440 450
ENGVPRYIPA KDLSAETAAG IDSKLAKQES LSHKLGAKKT DLPSSDREFY
460 470 480 490 500
NKAYDLLARI HQDLLDNKGR QVDFEALDNL LERLKDVSSD KVKLVDDILA
510 520 530 540 550
FLAPIRHPER LGKPNAQITY TDDEIQVAKL AGKYTTEDGY IFDPRDITSD
560 570 580 590 600
EGDAYVTPHM THSHWIKKDS LSEAERAAAQ AYAKEKGLTP PSTDHQDSGN
610 620 630 640 650
TEAKGAEAIY NRVKAAKKVP LDRMPYNLQY TVEVKNGSLI IPHYDHYHNI
660 670 680 690 700
KFEWFDEGLY EAPKGYSLED LLATVKYYVE HPNERPHSDN GFGNASDHVQ
710 720 730 740 750
RNKNGQADTN QTEKPNEEKP QTEKPEEDKE HDEVSEPTHP ESDEKENHVG
760 770 780 790 800
LNPSADNLYK PSTDTEETEE EAEDTTDEAE IPQVEHSVIN AKIAEAEALL
810 820 830 840 850
EKVTDSSIRQ NAVETLTGLK SSLLLGTKDN NTISAEVDSL LALLKESQPT
PIQ
SEQUENCE LENGTH - 853
CURRENT FIELD STATUS

CURRENT TRIAL STATUS
Phase II [4]
-
Immunisation of rhesus macaques [2]
-
Immunisation of mice in a sepsis model [4]
-
Immunisation of mice in a colonisation model [4]
-
Immunisation of toddlers with PhtD, PlyD1 and PcpA [2]

IMMUNE RESPONSE GENERATED
-
PhtD was proven to be highly immunogenic and have a capability to encourage protecting humoral immunity [2].
-
PhtD has been found to protect very effectively against pneumonia, nasopharyngeal colonisation, and sepsis [4] [5].
-
Mutants of PhtD show less virulence in mice challenged with pneumococcal infection. PhtD was also shown to protect mice from pneumococcal infection caused by a number of different serotypes.
-
Fusion proteins containing PhtD elicit an improved antibody response with higher antibody levels, when compared to control groups, with higher survival rates and a reduced bacterial load [4] [6].
-
PhtD combination vaccine immunising toddlers and infants proved to be safe and immunogenic [7].

MECHANISM OF VIRULENCE
-
PhtD is a lipoprotein. Lipoproteins have been shown to modulate inflammatory processes and aid in the movement of other virulence factors into the cell [1].
-
Mediates the adhesion of pneumococci to the respiratory tissue and mucosa [8].
-
Plays a role in zinc acquisition in pneumococcal virulence [9].
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