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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

litemol_screenshot.png

CURRENT FIELD STATUS

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CURRENT TRIAL STATUS

                     Phase 1                

  • Immunization of mice with LytA [7] [8].     

  • Chinchilla otitis media model [9].

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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].

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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]. 

RELATED GENE BANKS                                                                                                                                                    

RELATED ARTICLES                                                                                                                                                            

[1]         A. M. Whatmore and C. G. Dowson, “The autolysin-encoding gene (lytA) of Streptococcus pneumoniae displays restricted allelic variation despite localized recombination events with genes of pneumococcal bacteriophage encoding cell wall lytic enzymes,” Infection and Immunity, vol. 67, no. 9, pp. 4551–4556, 1999, doi: 10.1128/iai.67.9.4551-4556.1999.

 

[2]         K. K. Gosink, E. R. Mann, C. Guglielmo, E. I. Tuomanen, and H. R. Masure, “Role of novel choline binding proteins in virulence of Streptococcus pneumoniae,” Infection and Immunity, vol. 68, no. 10, pp. 5690–5695, 2000, doi: 10.1128/IAI.68.10.5690-5695.2000.

 

[3]         A. Vermassen, S. Leroy, R. Talon, C. Provot, M. Popowska, and M. Desvaux, “Cell wall hydrolases in bacteria: Insight on the diversity of cell wall amidases, glycosidases and peptidases toward peptidoglycan,” Frontiers in Microbiology, vol. 10, no. FEB. Frontiers Media S.A., p. 331, Feb. 28, 2019, doi: 10.3389/fmicb.2019.00331.

 

[4]         S. S. Tai, “Streptococcus pneumoniae protein vaccine candidates: Properties, activities and animal studies,” Critical Reviews in Microbiology, vol. 32, no. 3. Crit Rev Microbiol, pp. 139–153, Sep. 01, 2006, doi: 10.1080/10408410600822942.

 

[5]         M. J. Jedrzejas, “Pneumococcal Virulence Factors: Structure and Function,” Microbiology and Molecular Biology Reviews, vol. 65, no. 2, pp. 187–207, Jun. 2001, doi: 10.1128/mmbr.65.2.187-207.2001.

 

[6]         N. Cullin, J. Merritt, and J. Kreth, “Beyond Cell Division: the Ecological Roles of Autolysins in Oral Biofilm Communities,” Current Oral Health Reports, vol. 4, no. 1. Springer Science and Business Media B.V., pp. 14–21, Mar. 01, 2017, doi: 10.1007/s40496-017-0118-2.

 

[7]         B. Corsini, L. Aguinagalde, S. Ruiz, M. Domenech, and J. Yuste, “Vaccination with lyta, lytc, or pce of streptococcus pneumoniae protects against sepsis by inducing iggs that activate the complement system,” Vaccines, vol. 9, no. 2, pp. 1–15, 2021, doi: 10.3390/vaccines9020186.

 

[8]         A. M. Berry, R. A. Lock, D. Hansman, and J. C. Paton, “Contribution of autolysin to virulence of Streptococcus pneumoniae,” Infection and Immunity, vol. 57, no. 8, pp. 2324–2330, 1989, doi: 10.1128/iai.57.8.2324-2330.1989.

 

[9]          K. Sato, M. K. Quartey, C. L. Liebeler, C. T. Le, and G. Scott Giebink, “Roles of Autolysin and Pneumolysin in Middle Ear Inflammation Caused by a Type 3 Streptococcus pneumoniae

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