AUTOLYSIN
Gene Name - LytA
Cell Location - Cell wall - Autolysin is a well conserved secretary protein enzyme which bind the phosphoryl-choline moiety of the cell wall through their choline binding domain [1] [2].
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FUNCTION
Autolysin is a cell wall hydrolase which is hypothesized to contribute to a multitude of roles within Streptococcus pneumoniae, all of which contribute to the essential physiological functioning of the pathogen. It plays a role in the functions linked to:
• Cell division [3].
• The cell wall growth [4].
• Cell wall turnover, rearrangement, and degradation [1] [4] [5] .
• Daughter cell separation in the bacteria [2] [6].
LytA is also responsible for cellular autolysis. This is the process by which LytA facilitates the release of toxic substances. The subsequent damaging effects on host tissue lead to several major illnesses such as pneumonia, meningitis, or bacteraemia [1] [2] [5].
STRUCTURE
Click on the image for more information on the secondary and tertiary structure of Autolysin.
PROTEIN SEQUENCE
10 20 30 40 50
MEINVSKLRT DLPQVGVQPY RQVHAHSTGN PHSTVQNEAD YHWRKDPELG
60 70 80 90 100
FFSHIVGNGC IMQVGPVDNG AWDVGGGWNA ETYAAVELIE SHSTKEEFMT
110 120 130 140 150
DYRLYIELLR NLADEAGLPK TLDTGSLAGI KTHEYCTNNQ PNNHSDHVDP
160 170 180 190 200
YPYLAKWGIS REQFKHDIEN GLTIETGWQK NDTGYWYVHS DGSYPKDKFE
210 220 230 240 250
KINGTWYYFD SSGYMLADRW RKHTDGNWYW FDNSGEMATG WKKIADKWYY
260 270 280 290 300
FNEEGAMKTG WVKYKDTWYY LDAKEGAMVS NAFIQSADGT GWYYLKPDGT
310
LADKPEFTVE PDGLITVK
SEQUENCE LENGTH - 318
CURRENT FIELD STATUS

CURRENT TRIAL STATUS
Phase 1
-
Immunization of mice with LytA [7] [8].
-
Chinchilla otitis media model [9].

IMMUNE RESPONSE GENERATED
-
Mice immunized survived significantly longer than the control mice [7] [8].
-
Sera from mice immunized with each of the proteins investigated elicited strong IgG levels [7].
-
Chinchilla otitis media model showed that autolysin played a key role in middle ear inflammation [9].
-
Autolysin displayed the same level of protection as pneumolysin in testing. The addition of pneumolysin showed no additional protective capabilities in the animal [1].

MECHANISM OF VIRULENCE
-
Mediates the release of components from the cell wall which have been shown to be extremely inflammatory in animal models [2].
-
Aids in cell lysis which subsequently releases toxic substances and virulence factors [1] [2].
-
Mutations of LytA show significantly less virulence and can be rapidly cleared and do not enter the bloodstream proving LytA plays a role in virulence [1].
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