Dual Functions of Discoidinolysin, a Cholesterol-dependent Cytolysin with N-terminal Discoidin Domain Produced from Strain Nm-76

Overview

Journal J Oral Microbiol

Specialty Dentistry

Date 2022 Aug 8

PMID 35937899

Authors

Atsushi Tabata

Airi Matsumoto

Ai Fujimoto

Kazuto Ohkura

Takuya Ikeda

Hiroki Oda

Shuto Yokohata

Miho Kobayashi

Toshifumi Tomoyasu

Ayuko Takao

Hisashi Ohkuni

Hideaki Nagamune

Affiliations

Soon will be listed here.

Abstract

Background: Some strains of exhibit β-hemolysis due to the β-hemolytic activity of cholesterol-dependent cytolysin (CDC). Recently, a gene encoding an atypical lectinolysin-related CDC was found in strain Nm-76. However, the product of this gene remains uncharacterized. We aimed to characterize this atypical CDC and its molecular functions and contribution to the pathogenicity of strain Nm-76.

Methods: Phylogenetic analysis of the CDC gene was conducted based on the web-deposited information. The molecular characteristics of CDC were investigated using a gene-deletion mutant strain and recombinant proteins expressed in .

Results: The gene encoding CDC found in Nm-76 and its homolog are distributed among many strains. This CDC is phylogenetically different from other previously characterized CDCs, such as -derived human platelet aggregation factor (Sm-hPAF)/lectinolysin and mitilysin. Because this CDC possesses an additional N-terminal domain, including a discoidin motif, it was termed discoidinolysin (DLY). In addition to the preferential lysis of human cells, DLY displayed N-terminal domain-dependent facilitation of human erythrocyte aggregation and intercellular associations between human cells.

Conclusion: DLY functions as a hemolysin/cytolysin and erythrocyte aggregation/intercellular association molecule. This dual-function DLY could be an additional virulence factor in .

Citing Articles

Characterization of tigurilysin, a novel human CD59-specific cholesterol-dependent cytolysin, reveals a role for host specificity in augmenting toxin activity.

Shahi I, Dongas S, Ilmain J, Torres V, Ratner A Microbiology (Reading). 2023; 169(9).

PMID: 37702594 PMC: 10569062. DOI: 10.1099/mic.0.001393.

Characterization of Tigurilysin, a Novel Human CD59-Specific Cholesterol-Dependent Cytolysin, Reveals a Role for Host Specificity in Augmenting Toxin Activity.

Shahi I, Dongas S, Ilmain J, Torres V, Ratner A bioRxiv. 2023; .

PMID: 37546867 PMC: 10401958. DOI: 10.1101/2023.06.21.545930.

References

Baumgartner S, Hofmann K, Chiquet-Ehrismann R, Bucher P . The discoidin domain family revisited: new members from prokaryotes and a homology-based fold prediction. Protein Sci. 1998; 7(7):1626-31. PMC: 2144056. DOI: 10.1002/pro.5560070717. View

Dupont C, Michon A, Normandin M, Salom G, Latypov M, Chiron R . Streptococcus pseudopneumoniae, an opportunistic pathogen in patients with cystic fibrosis. J Cyst Fibros. 2019; 19(4):e28-e31. DOI: 10.1016/j.jcf.2019.11.004. View

Matsui N, Ito M, Kuramae H, Inukai T, Sakai A, Okugawa M . Infective endocarditis caused by multidrug-resistant Streptococcus mitis in a combined immunocompromised patient: an autopsy case report. J Infect Chemother. 2012; 19(2):321-5. DOI: 10.1007/s10156-012-0465-9. View

Gonzales-Siles L, Karlsson R, Schmidt P, Salva-Serra F, Jaen-Luchoro D, Skovbjerg S . A Pangenome Approach for Discerning Species-Unique Gene Markers for Identifications of and . Front Cell Infect Microbiol. 2020; 10:222. PMC: 7248185. DOI: 10.3389/fcimb.2020.00222. View

Morales M, Martin-Galiano A, Domenech M, Garcia E . Insights into the Evolutionary Relationships of LytA Autolysin and Ply Pneumolysin-Like Genes in Streptococcus pneumoniae and Related Streptococci. Genome Biol Evol. 2015; 7(9):2747-61. PMC: 4607534. DOI: 10.1093/gbe/evv178. View

Ohkuni H, Todome Y, Okibayashi F, Watanabe Y, Ohtani N, Ishikawa T . Purification and partial characterization of a novel human platelet aggregation factor in the extracellular products of Streptococcus mitis, strain Nm-65. FEMS Immunol Med Microbiol. 1997; 17(2):121-9. DOI: 10.1111/j.1574-695X.1997.tb01004.x. View

LaChapelle S, Tweten R, Hotze E . Intermedilysin-receptor interactions during assembly of the pore complex: assembly intermediates increase host cell susceptibility to complement-mediated lysis. J Biol Chem. 2009; 284(19):12719-26. PMC: 2676001. DOI: 10.1074/jbc.M900772200. View

Lim Y, Park S, Shin J, Ji S, Jo E, Chang Y . Streptococcus koreensis sp. nov., Isolated from Human Subgingival Dental Plaque of Periodontitis Lesion. Curr Microbiol. 2019; 76(12):1531-1536. DOI: 10.1007/s00284-019-01778-6. View

Garriss G, Nannapaneni P, Simoes A, Browall S, Subramanian K, Sa-Leao R . Genomic Characterization of the Emerging Pathogen Streptococcus pseudopneumoniae. mBio. 2019; 10(3). PMC: 6593409. DOI: 10.1128/mBio.01286-19. View

10.

Jefferies J, Nieminen L, Kirkham L, Johnston C, Smith A, Mitchell T . Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis. J Bacteriol. 2006; 189(2):627-32. PMC: 1797409. DOI: 10.1128/JB.01092-06. View

11.

Nagamune H, Ohnishi C, Katsuura A, Fushitani K, Whiley R, Tsuji A . Intermedilysin, a novel cytotoxin specific for human cells secreted by Streptococcus intermedius UNS46 isolated from a human liver abscess. Infect Immun. 1996; 64(8):3093-100. PMC: 174193. DOI: 10.1128/iai.64.8.3093-3100.1996. View

12.

Whatmore A, Efstratiou A, Pickerill A, Broughton K, WOODARD G, Sturgeon D . Genetic relationships between clinical isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: characterization of "Atypical" pneumococci and organisms allied to S. mitis harboring S. pneumoniae virulence factor-encoding.... Infect Immun. 2000; 68(3):1374-82. PMC: 97291. DOI: 10.1128/IAI.68.3.1374-1382.2000. View

13.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

14.

Park S, Lim Y, Shin J, Chang Y, Shin Y, Paek J . Streptococcus gwangjuense sp. nov., Isolated from Human Pericoronitis. Curr Microbiol. 2019; 76(7):799-803. DOI: 10.1007/s00284-019-01687-8. View

15.

Ohkura K, Hori H, Nagamune H . Molecular dynamics of human-specific cytolysin: analysis of membrane binding motif for therapeutic application. Anticancer Res. 2007; 26(6A):4055-62. View

16.

Kilian M, Tettelin H . Identification of Virulence-Associated Properties by Comparative Genome Analysis of Streptococcus pneumoniae, S. pseudopneumoniae, S. mitis, Three S. oralis Subspecies, and . mBio. 2019; 10(5). PMC: 6722419. DOI: 10.1128/mBio.01985-19. View

17.

Matsumoto A, Tabata A, Ohkura K, Oda H, Kodama C, Ohkuni H . Molecular characteristics of an adhesion molecule containing cholesterol-dependent cytolysin-motif produced by mitis group streptococci. Microbiol Immunol. 2020; 65(2):61-75. DOI: 10.1111/1348-0421.12868. View

18.

Jensen A, Scholz C, Kilian M . Re-evaluation of the taxonomy of the Mitis group of the genus Streptococcus based on whole genome phylogenetic analyses, and proposed reclassification of Streptococcus dentisani as Streptococcus oralis subsp. dentisani comb. nov., Streptococcus.... Int J Syst Evol Microbiol. 2016; 66(11):4803-4820. DOI: 10.1099/ijsem.0.001433. View

19.

Zou Y, Sun Y, Qi H, Liu D, Tian H, Wang N . sp. nov. E24 Isolated From the Oropharynx of Healthy Chinese Children. Front Microbiol. 2020; 11:563213. PMC: 7550633. DOI: 10.3389/fmicb.2020.563213. View

20.

Tabata A, Ohkura K, Ohkubo Y, Tomoyasu T, Ohkuni H, Whiley R . The diversity of receptor recognition in cholesterol-dependent cytolysins. Microbiol Immunol. 2014; 58(3):155-71. DOI: 10.1111/1348-0421.12131. View