Role of SrtA in Pathogenicity of

Overview

Journal Microorganisms

Specialty Microbiology

Date 2020 Dec 16

PMID 33322541

Citations 7

Authors

Muzaffar Hussain

Christian Kohler

Karsten Becker

Affiliations

Soon will be listed here.

Abstract

Among coagulase-negative staphylococci (CoNS), has a special position as causative agent of aggressive courses of infectious endocarditis (IE) more reminiscent of IEs caused by than those by CoNS. To initiate colonization and invasion, bacterial cell surface proteins are required; however, only little is known about adhesion of to biotic surfaces. Cell surface proteins containing the LPXTG anchor motif are covalently attached to the cell wall by sortases. Here, we report the functionality of sortase A (SrtA) to link LPXTG substrates to the cell wall. To determine the role of SrtA dependent surface proteins in biofilm formation and binding eukaryotic cells, we generated SrtA-deficient mutants (Δ). These mutants formed a smaller amount of biofilm and bound less to immobilized fibronectin, fibrinogen, and vitronectin. Furthermore, SrtA absence affected the gene expression of two different adhesins on transcription level. Surprisingly, we found no decreased adherence and invasion in human cell lines, probably caused by the upregulation of further adhesins in Δ mutant strains. In conclusion, the functionality of SrtA in anchoring LPXTG substrates to the cell wall let us define it as the pathogen's housekeeping sortase.

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References

Perry A, Ton-That H, Mazmanian S, Schneewind O . Anchoring of surface proteins to the cell wall of Staphylococcus aureus. III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring. J Biol Chem. 2002; 277(18):16241-8. DOI: 10.1074/jbc.M109194200. View

van der Mee-Marquet N, ACHARD A, Mereghetti L, Danton A, Minier M, Quentin R . Staphylococcus lugdunensis infections: high frequency of inguinal area carriage. J Clin Microbiol. 2003; 41(4):1404-9. PMC: 153917. DOI: 10.1128/JCM.41.4.1404-1409.2003. View

Weiss W, Lenoy E, Murphy T, Tardio L, Burgio P, Projan S . Effect of srtA and srtB gene expression on the virulence of Staphylococcus aureus in animal models of infection. J Antimicrob Chemother. 2004; 53(3):480-6. DOI: 10.1093/jac/dkh078. View

Hussain M, Schafer D, Juuti K, Peters G, Haslinger-Loffler B, Kuusela P . Expression of Pls (plasmin sensitive) in Staphylococcus aureus negative for pls reduces adherence and cellular invasion and acts by steric hindrance. J Infect Dis. 2009; 200(1):107-17. DOI: 10.1086/599359. View

Heilbronner S, Hanses F, Monk I, Speziale P, Foster T . Sortase A promotes virulence in experimental Staphylococcus lugdunensis endocarditis. Microbiology (Reading). 2013; 159(Pt 10):2141-2152. DOI: 10.1099/mic.0.070292-0. View

Hussain M, Haggar A, Heilmann C, Peters G, Flock J, Herrmann M . Insertional inactivation of Eap in Staphylococcus aureus strain Newman confers reduced staphylococcal binding to fibroblasts. Infect Immun. 2002; 70(6):2933-40. PMC: 128007. DOI: 10.1128/IAI.70.6.2933-2940.2002. View

Hirakawa H, Ishikawa S, Nagamune T . Design of Ca2+-independent Staphylococcus aureus sortase A mutants. Biotechnol Bioeng. 2012; 109(12):2955-61. DOI: 10.1002/bit.24585. View

Palma M, Nozohoor S, Schennings T, Heimdahl A, Flock J . Lack of the extracellular 19-kilodalton fibrinogen-binding protein from Staphylococcus aureus decreases virulence in experimental wound infection. Infect Immun. 1996; 64(12):5284-9. PMC: 174520. DOI: 10.1128/iai.64.12.5284-5289.1996. View

Spirig T, Weiner E, Clubb R . Sortase enzymes in Gram-positive bacteria. Mol Microbiol. 2011; 82(5):1044-59. PMC: 3590066. DOI: 10.1111/j.1365-2958.2011.07887.x. View

10.

Becker K, Heilmann C, Peters G . Coagulase-negative staphylococci. Clin Microbiol Rev. 2014; 27(4):870-926. PMC: 4187637. DOI: 10.1128/CMR.00109-13. View

11.

Ton-That H, Liu G, Mazmanian S, Faull K, Schneewind O . Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif. Proc Natl Acad Sci U S A. 1999; 96(22):12424-9. PMC: 22937. DOI: 10.1073/pnas.96.22.12424. View

12.

Sundqvist M, Bieber L, Smyth R, Kahlmeter G . Detection and identification of Staphylococcus lugdunensis are not hampered by use of defibrinated horse blood in blood agar plates. J Clin Microbiol. 2010; 48(5):1987-8. PMC: 2863894. DOI: 10.1128/JCM.02307-09. View

13.

Kim S, Shin D, Oh M, Chung S, Lee J, Oh K . Inhibition of the bacterial surface protein anchoring transpeptidase sortase by isoquinoline alkaloids. Biosci Biotechnol Biochem. 2004; 68(2):421-4. DOI: 10.1271/bbb.68.421. View

14.

Nobbs A, Vajna R, Johnson J, Zhang Y, Erlandsen S, Oli M . Consequences of a sortase A mutation in Streptococcus gordonii. Microbiology (Reading). 2007; 153(Pt 12):4088-4097. DOI: 10.1099/mic.0.2007/007252-0. View

15.

Mazmanian S, Liu G, Ton-That H, Schneewind O . Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science. 1999; 285(5428):760-3. DOI: 10.1126/science.285.5428.760. View

16.

Maresso A, Schneewind O . Sortase as a target of anti-infective therapy. Pharmacol Rev. 2008; 60(1):128-41. DOI: 10.1124/pr.107.07110. View

17.

Oshida T, Sugai M, Komatsuzawa H, Hong Y, Suginaka H, Tomasz A . A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase domain and an endo-beta-N-acetylglucosaminidase domain: cloning, sequence analysis, and characterization. Proc Natl Acad Sci U S A. 1995; 92(1):285-9. PMC: 42863. DOI: 10.1073/pnas.92.1.285. View

18.

Nilsson M, Bjerketorp J, Guss B, Frykberg L . A fibrinogen-binding protein of Staphylococcus lugdunensis. FEMS Microbiol Lett. 2004; 241(1):87-93. DOI: 10.1016/j.femsle.2004.10.008. View

19.

Mazmanian S, Ton-That H, Su K, Schneewind O . An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc Natl Acad Sci U S A. 2002; 99(4):2293-8. PMC: 122358. DOI: 10.1073/pnas.032523999. View

20.

Khan S, Novick R . Terminal nucleotide sequences of Tn551, a transposon specifying erythromycin resistance in Staphylococcus aureus: homology with Tn3. Plasmid. 1980; 4(2):148-54. DOI: 10.1016/0147-619x(80)90004-9. View