Editing Autolysin

{{Short description|Class of enzymes}}
'''Autolysins''' are endogenous lytic [[enzyme]]s that break down the [[peptidoglycan]] components of [[Cell (biology)|biological cells]] which enables the separation of daughter cells following cell division.<ref>{{cite journal | vauthors = Jaenicke L, Kuhne W, Spessert R, Wahle U, Waffenschmidt S | title = Cell-wall lytic enzymes (autolysins) of Chlamydomonas reinhardtii are (hydroxy)proline-specific proteases | journal = European Journal of Biochemistry | volume = 170 | issue = 1–2 | pages = 485–491 | date = December 1987 | pmid = 3319620 | doi = 10.1111/j.1432-1033.1987.tb13725.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Buchanan MJ, Imam SH, Eskue WA, Snell WJ | title = Activation of the cell wall degrading protease, lysin, during sexual signalling in Chlamydomonas: the enzyme is stored as an inactive, higher relative molecular mass precursor in the periplasm | journal = The Journal of Cell Biology | volume = 108 | issue = 1 | pages = 199–207 | date = January 1989 | pmid = 2910877 | pmc = 2115355 | doi = 10.1083/jcb.108.1.199 }}</ref><ref>{{cite book | chapter = Gametolysin | title = Handbook of Proteolytic Enzymes | vauthors = Matsuda Y | year = 1998 |pages = 1140–1143 |veditors= Barrett AJ, Rawlings ND, Woessner JF |publisher = Academic Press |location = London }}</ref><ref name=":0">{{cite journal | vauthors = Clarke AJ | title = The "hole" story of predatory outer-membrane vesicles | journal = Canadian Journal of Microbiology | volume = 64 | issue = 9 | pages = 589–599 | date = September 2018 | pmid = 30169125 | doi = 10.1139/cjm-2017-0466 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Porayath C, Suresh MK, Biswas R, Nair BG, Mishra N, Pal S | title = Autolysin mediated adherence of Staphylococcus aureus with Fibronectin, Gelatin and Heparin | journal = International Journal of Biological Macromolecules | volume = 110 | pages = 179–184 | date = April 2018 | pmid = 29398086 | pmc = 5864509 | doi = 10.1016/j.ijbiomac.2018.01.047 }}</ref> They are involved in cell growth, cell wall metabolism, cell division and separation, as well as peptidoglycan turnover and have similar functions to lysozymes.<ref name=":1">{{cite journal | vauthors = Smith TJ, Blackman SA, Foster SJ | title = Autolysins of Bacillus subtilis: multiple enzymes with multiple functions | journal = Microbiology | volume = 146 ( Pt 2) | issue = 2 | pages = 249–262 | date = February 2000 | pmid = 10708363 | doi = 10.1099/00221287-146-2-249 | doi-access = free }}</ref>

Autolysin is formed from the precursor gene, Atl. [[Amidase]]s (EC 3.5.1.28), gametolysin (EC 3.4.24.38), and glucosaminidase are considered as types of autolysins.<ref name=":0" /><ref name=":1" />

== Function and mechanisms ==
[[File:Peptidoglycan-membrane.png|thumb|331x331px|Peptidoglycan Cell Wall and their Cross Linked Peptides]]
Autolysins exist in all [[bacteria]] containing [[peptidoglycan]] and are potentially considered as lethal enzymes when uncontrolled.<ref>{{cite journal | vauthors = Haghighat S, Siadat SD, Sorkhabadi SM, Sepahi AA, Mahdavi M | title = Cloning, expression and purification of autolysin from methicillin-resistant Staphylococcus aureus: potency and challenge study in Balb/c mice | journal = Molecular Immunology | volume = 82 | pages = 10–18 | date = February 2017 | pmid = 28006655 | doi = 10.1016/j.molimm.2016.12.013 | s2cid = 36593600 }}</ref> They target the glycosidic bonds as well as the cross-linked peptides of the peptidoglycan matrix.<ref name="pmid24692449">{{cite journal | vauthors = Atilano ML, Pereira PM, Vaz F, Catalão MJ, Reed P, Grilo IR, Sobral RG, Ligoxygakis P, Pinho MG, Filipe SR | display-authors = 6 | title = Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system | journal = eLife | volume = 3 | pages = e02277 | date = April 2014 | pmid = 24692449 | pmc = 3971415 | doi = 10.7554/eLife.02277 | doi-access = free }}</ref> The peptidoglycan matrix functions for cell wall stability to protect from turgor changes and carries out function for immunological defense.<ref>{{cite journal | vauthors = Zhang Y, Zhong X, Lu P, Zhu Y, Dong W, Roy S, Hejair HM, Pan Z, Ma J, Yao H | display-authors = 6 | title = A novel autolysin AtlA<sub>SS</sub> mediates bacterial cell separation during cell division and contributes to full virulence in Streptococcus suis | journal = Veterinary Microbiology | volume = 234 | pages = 92–100 | date = July 2019 | pmid = 31213278 | doi = 10.1016/j.vetmic.2019.05.020 | s2cid = 182382454 }}</ref><ref>{{cite book | vauthors = Pazos M, Peters K | title = Bacterial Cell Walls and Membranes | chapter = Peptidoglycan | series = Subcellular Biochemistry | volume = 92 | pages = 127–168 | date = 2019 | pmid = 31214986 | doi = 10.1007/978-3-030-18768-2_5  | publisher = Springer International Publishing | isbn = 978-3-030-18767-5 | s2cid = 239142525 | editor-first = Andreas | editor-last = Kuhn }}</ref> These enzymes break down the peptidoglycan matrix in small sections to allow for peptidoglycan biosynthesis.<ref name=":0" /> Autolysins breaks down old peptidoglycan which allows for the formation of newer peptidoglycan for cell growth and elongation. This is called cell wall turnover.<ref name=":1" /> Autolysins do this by hydrolyzing the β-(1,4) glycosidic bond of the peptidoglycan cell wall and the linkage between N-acetylmuramoyl residues and L-amino acid residues of certain cell-wall glycopeptides.<ref name=":0" /> This enzyme [[catalysis|catalyses]] the following [[chemical reaction]]:

: Cleavage of the [[proline]]- and [[hydroxyproline]]-rich proteins of the ''[[Chlamydomonas]]'' [[cell wall]]; also cleaves [[azocasein]], [[gelatin]] and Leu-Trp-Met-Arg-Phe-Ala

This glycoprotein is present in ''[[Chlamydomonas reinhardtii]]'' [[gamete]]s.

[[Gram-positive]] bacteria regulate autolysins with [[teichoic acid]] molecules attached to the tetrapeptide of the peptidoglycan matrix.

The [[antibiotic]]s complestatin and [[corbomycin]] prevent autolysin from remodeling the cell wall by binding to peptidoglycan, therefore stopping bacterial growth.<ref name="CulpWaglechner2020">{{cite journal | vauthors = Culp EJ, Waglechner N, Wang W, Fiebig-Comyn AA, Hsu YP, Koteva K, Sychantha D, Coombes BK, Van Nieuwenhze MS, Brun YV, Wright GD | display-authors = 6 | title = Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling | journal = Nature | volume = 578 | issue = 7796 | pages = 582–587 | date = February 2020 | pmid = 32051588 | doi = 10.1038/s41586-020-1990-9 | s2cid = 211089119 | bibcode = 2020Natur.578..582C }}</ref> The amide linkages between stem peptide and lactyl moiety of muramoyl residue are cleaved by [[N-acetylmuramoyl-L-alanine amidase|N-acetylmuramoyl-l-alanine amidases]] and partakes in cell separation and the dissociation of the cell septum.<ref name=":0" /> There are 5 types of autolysins that contribute to cell separation of daughter cells, LytC, LytD, LytE, and LytF.<ref name=":1" />

In a study conducted with mice, those that were immunized with autolysin were able to survive longer than the infected mice. This study was able to support as evidence autolysin's contribution in virulence and potential for vaccine antigen.<ref name=":3">{{cite journal | vauthors = Berry AM, Lock RA, Hansman D, Paton JC | title = Contribution of autolysin to virulence of Streptococcus pneumoniae | journal = Infection and Immunity | volume = 57 | issue = 8 | pages = 2324–2330 | date = August 1989 | pmid = 2568343 | pmc = 313450 | doi = 10.1128/iai.57.8.2324-2330.1989 | doi-access = free }}</ref>

=== Lysis of mother cell ===
{{Infobox enzyme|name=N-acetylmuramoyl-L-alanine amidase|EC_number=3.5.1.28|CAS_number=9013-25-6|GO_code=GO:0008745}}
LytC and CwlC are two [[amidase]]s from the LytC family that hydrolyze the peptidoglycan of the mother cell wall to allow for the release of the mature endospore. CwlC is directly found in the mother cell wall.<ref name=":1" />

=== Motility ===
Expression of lytC, lytD, and lytF genes together leads to flagellar motility and is controlled by the activity of the chemotaxis sigma factor,  σ<sup>D</sup>. The activity of this sigma factor peaks at the start of the stationary phase.<ref name=":1" />

=== Potential lethality ===
Autolysins are naturally produced by peptidoglycan containing bacteria, but excessive amounts will degrade the peptidoglycan matrix and cause the cell to burst due to [[osmotic pressure]]. Previous studies have found that the byproducts of autolysin during cell wall breakdown are highly immunogenic.<ref name=":3" /> When observed in the bacteria, ''[[Bacillus subtilis]]'', there were potentially lethal amounts of autolysin found in the cell walls.<ref name=":1" /> In ''Streptococcus pneumoniae'' it was found that N-acetylmuramoyl-l-alanine amidase, a cell wall autolysin, could assist in pathogenesis due to its ability to break down the wall or lyse a portion of the invading pneumococci and release potentially lethal toxins into the cell. Researchers studied the function, structure, and cloning ability through ''Escherichia coli'' and also determined its nucleotide sequence.<ref name=":3" />

== Families ==

=== LytC amidase family ===

==== LytC ====
LytC as well as LytD are considered as two major autolysins that contribute to vegetative cell wall growth and account for 95% of the autolytic activity in B. subtilis. LytC is found in the cell wall. LytB, a non-autolysin, was found to enhance LytC activity.<ref name=":1" /> LytC and LytA interact and function together for lysis and cell death.<ref>{{cite journal | vauthors = García P, Paz González M, García E, García JL, López R | title = The molecular characterization of the first autolytic lysozyme of Streptococcus pneumoniae reveals evolutionary mobile domains | journal = Molecular Microbiology | volume = 33 | issue = 1 | pages = 128–138 | date = July 1999 | pmid = 10411730 | doi = 10.1046/j.1365-2958.1999.01455.x | doi-access = free }}</ref>{{Infobox enzyme
| Name = Gametolysin
| EC_number = 3.4.24.38
| CAS_number = 97089-74-2
| IUBMB_EC_number = 3/4/24/38
| GO_code = 
| image = 
| width = 
| caption =
}}

==== CwlC ====
CwlC is found in the mother cell wall and functions for the lysis of the mother cell wall.<ref name=":1" /> CwlC does not have a signal sequence but participates in late sporulation and is present in the cell wall.<ref name=":2">{{cite journal | vauthors = Kuroda A, Asami Y, Sekiguchi J | title = Molecular cloning of a sporulation-specific cell wall hydrolase gene of Bacillus subtilis | journal = Journal of Bacteriology | volume = 175 | issue = 19 | pages = 6260–6268 | date = October 1993 | pmid = 8407798 | pmc = 206722 | doi = 10.1128/jb.175.19.6260-6268.1993 }}</ref><ref>{{cite journal | vauthors = Smith TJ, Foster SJ | title = Characterization of the involvement of two compensatory autolysins in mother cell lysis during sporulation of Bacillus subtilis 168 | journal = Journal of Bacteriology | volume = 177 | issue = 13 | pages = 3855–3862 | date = July 1995 | pmid = 7601853 | pmc = 177106 | doi = 10.1128/jb.177.13.3855-3862.1995 }}</ref> It was found in B. subtilis that CwlC is able to hydrolyze both vegetative cell walls and spore peptidoglycan.<ref name=":2" />

=== LytD glucosaminidase family ===
This family of autolysin consist of only LytD itself. LytD functions for vegetative growth. Autolytic activity is found within the C-terminal region with catalytic domain homologous to the glucosaminidase domain. LytD is found in the cell wall. LytD activity was studied in B. subtilis and glucosaminidase activity was found in mature glycan strands due to the presence of MurNAc at the nonreducing ends.<ref name=":1" />

== See also ==

* [[N-acetylmuramoyl-L-alanine amidase|N-acetylmuramoyl-l-alanine amidase]]
* [[Enzyme]]

== References ==
{{reflist}}

== External links ==
* {{MeshName|Gametolysin}}

{{Metalloendopeptidases}}
{{Enzymes}}
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[[Category:EC 3.4.24]]
[[Category:Bacterial enzymes]]