PNEUMOLYSIN
Gene Name - Ply
Cell Location - Located in the cell membrane, pneumolysin is a multi-pass membrane protein. Ply is a secretory enzyme that is not surface exposed [1].
FUNCTION
Pneumolysin is attributed to many biological functions in S. pneumoniae. It plays a role in Fc binding, complement fixation and activation, and damaging epithelial cells. It plays a role in causing infections of the eye and pneumococcal infection caused by intranasal, intratracheal, and parenteral routes. It is involved in many aspects of infection by pneumococci such as transmission and colonisation [2].
It is a cholesterol-dependent cytolysin (CDC) toxin which mediates cell death in the host by attaching to membrane cholesterol and oligomerizing. This then form lytic pores in the cell membrane of the host. The formation of these pores then can lead to the loss of cytoplasmic content and an invasion by extracellular ions. It also facilitates pathogenesis of pneumococcal diseases by triggering the activation of inflammatory immune cells and controlling inflammatory response [3].
STRUCTURE
Click on the image for more information on the secondary and tertiary structure of Pneumolysin.
PROTEIN SEQUENCE
10 20 30 40 50
MANKAVNDFI LAMNYDKKKL LTHQGESIEN RFIKEGNQLP DEFVVIERKK
60 70 80 90 100
RSLSTNTSDI SVTATNDSRL YPGALLVVDE TLLENNPTLL AVDRAPMTYS
110 120 130 140 150
IDLPGLASSD SFLQVEDPSN SSVRGAVNDL LAKWHQDYGQ VNNVPARMQY
160 170 180 190 200
EKITAHSMEQ LKVKFGSDFE KTGNSLDIDF NSVHSGEKQI QIVNFKQIYY
210 220 230 240 250
TVSVDAVKNP GDVFQDTVTV EDLKQRGISA ERPLVYISSV AYGRQVYLKL
260 270 280 290 300
ETTSKSDEVE AAFEALIKGV KVAPQTEWKQ ILDNTEVKAV ILGGDPSSGA
310 320 330 340 350
RVVTGKVDMV EDLIQEGSRF TADHPGLPIS YTTSFLRDNV VATFQNSTDY
360 370 380 390 400
VETKVTAYRN GDLLLDHSGA YVAQYYITWD ELSYDHQGKE VLTPKAWDRN
410 420 430 440 450
GQDLTAHFTT SIPLKGNVRN LSVKIRECTG LAWEWWRTVY EKTDLPLVRK
460 470
RTISIWGTTL YPQVEDKVEN D
SEQUENCE LENGTH - 471
CURRENT FIELD STATUS

CURRENT TRIAL STATUS
Phase I [4]
-
Combination of Ply with PspA as a vaccine candidate [4]
-
Immunisation of mice with Ply
-
In vivo sepsis model

IMMUNE RESPONSE GENERATED
-
Mice immunised with a fusion of Ply and PspA produce significant levels of protective antibodies, the fusion proteins increase immune response, and show high levels of protection against fatal challenge.
-
Mice infected with S. pneumoniae, Ply antibodies protected mice from adverse fatal effects caused by the purified toxins. Mice also showed significantly greater survival times than control mice [5] [6].
-
In vivo sepsis models show an increase of survival times when mice are immunised with reduced-toxicity variants of pneumolysin [7].
-
Immunisation with Ply shows noteworthy reduction in lung burden caused by Streptococcus pneumoniae in infected mice [7].
-
Elicits protection against more than one serotype.
MECHANISM OF VIRULENCE
-
Helps with surface adhesion and forms pores in the membrane of the cell.
-
Inhibits the response of neutrophils which provide the primary host defence against the pathogen.
-
Interferes with the rapid multiplication of antibody cells and the generation of antibodies.
-
Hinders/prevents ciliary epithelial cell beat frequency.
-
Toxic for epithelial cells found in the alveoli of the lung [4].
-
Pneumolysin binds to cholesterol within the plasma membrane of host cells and assembles to form trans‐membrane pores, which can lead to Ca2+ influx and cell death [8] [9].
RELATED ARTICLES
Bibliography