Principle and potential applications of the non-classical protein secretory pathway in bacteria
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In addition to the extracellular proteins secreted by known secretory pathways, a number of cytoplasmic proteins without predicable or known signal sequences or secretory motifs have been found in the extracellular milieu, and were consequently classified as non-classically secreted proteins. Non-classical protein secretion is considered to be a general, conserved cellular phenomenon in both eukaryotes and prokaryotes. There are several research hotspots on the non-classical protein secretory pathway, and the most important two of them are the recognition principle of substrate proteins and possible secretory mechanisms. To date, researchers have made some progress in understanding the characteristics of these proteins. For example, it was discovered that many non-classically secreted proteins exist and are secreted in multimeric form. Some of these proteins prefer to be clustered and exported at the poles and the septum of the cell. The majority of these proteins play different functions when they are in the intra- and extracellular environments, and several of their functions are related to survival and pathogenicity. Furthermore, non-classically secreted proteins can be used as leading proteins to guide a POI (protein of interest) out of the cells, which provides a novel strategy for protein secretion with potential applications in the industry. Summarizing these findings, this review emphasizes the hot spots related to non-classically secreted proteins in bacteria, lists the most important hypotheses on the selection and secretion mechanisms of non-classically secreted proteins, and put forward their potential applications.
KeywordsNon-classical secretion pathway Secretion mechanism Protein secretion Signal-less proteins
The authors wish to express their gratitude for the great support received from the funding agencies.
Availability of data and materials
This is a review article without original data.
QK and DZ conceived the review; QK and DZ wrote the manuscript.
This work was supported by the National Key R&D Program of China (2018YFA0900302, 2018YFD0901001), the National Natural Science Foundation of China (NSFC 31800086), the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC45300), and the Science and Technology Service Network (STS) Initiative of the Chinese Academy of Sciences (CAS) (KFJ-STS-ZDTP-065).
Compliance with ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
- Beck HC, Madsen SM, Glenting J, Petersen J, Israelsen H, Norrelykke MR, Antonsson M, Hansen AM (2009) Proteomic analysis of cell surface-associated proteins from probiotic Lactobacillus plantarum. FEMS Microbiol Lett 297(1):61–66. https://doi.org/10.1111/j.1574-6968.2009.01662.x CrossRefPubMedGoogle Scholar
- Callahan B, Nguyen K, Collins A, Valdes K, Caplow M, Crossman DK, Steyn AJ, Eisele L, Derbyshire KM (2010) Conservation of structure and protein-protein interactions mediated by the secreted mycobacterial proteins EsxA, EsxB, and EspA. J Bacteriol 192(1):326–335. https://doi.org/10.1128/JB.01032-09 CrossRefPubMedGoogle Scholar
- Candela M, Centanni M, Fiori J, Biagi E, Turroni S, Orrico C, Bergmann S, Hammerschmidt S, Brigidi P (2010) DnaK from Bifidobacterium animalis subsp. lactis is a surface-exposed human plasminogen receptor upregulated in response to bile salts. Microbiology 156(Pt 6):1609–1618. https://doi.org/10.1099/mic.0.038307-0 CrossRefPubMedGoogle Scholar
- Cui J, Wang G, Chen H, Chen J, Gu Z, Chen W, Zhang H (2015) Effect of non-classical secreted proteins on LipaseA secretion. Acta Microbiol Sin 55(2):198–204Google Scholar
- Ebner P, Rinker J, Nguyen MT, Popella P, Nega M, Luqman A, Schittek B, Di Marco M, Stevanovic S, Gotz F (2016b) Excreted cytoplasmic proteins contribute to pathogenicity in Staphylococcus aureus. Infect Immun 84(6):1672–1681. https://doi.org/10.1128/IAI.00138-16 CrossRefPubMedPubMedCentralGoogle Scholar
- Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, Smith S, Sherman DR (2004) Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Microbiol 51(2):359–370. https://doi.org/10.1046/j.1365-2958.2003.03844.x CrossRefPubMedPubMedCentralGoogle Scholar
- Hamilton JJ, Marlow VL, Owen RA, Costa Mde A, Guo M, Buchanan G, Chandra G, Trost M, Coulthurst SJ, Palmer T, Stanley-Wall NR, Sargent F (2014) A holin and an endopeptidase are essential for chitinolytic protein secretion in Serratia marcescens. J Cell Biol 207(5):615–626. https://doi.org/10.1083/jcb.201404127 CrossRefPubMedPubMedCentralGoogle Scholar
- Harth G, Horwitz MA (1997) Expression and efficient export of enzymatically active Mycobacterium tuberculosis glutamine synthetase in Mycobacterium smegmatis and evidence that the information for export is contained within the protein. J Biol Chem 272(36):22728–22735. https://doi.org/10.1074/jbc.272.36.22728 CrossRefPubMedGoogle Scholar
- Harth G, Horwitz MA (1999) Export of recombinant Mycobacterium tuberculosis superoxide dismutase is dependent upon both information in the protein and mycobacterial export machinery. A model for studying export of leaderless proteins by pathogenic mycobacteria. J Biol Chem 274(7):4281–4292. https://doi.org/10.1074/jbc.274.7.4281 CrossRefPubMedGoogle Scholar
- Jeiranikhameneh M, Razavi MR, Irani S, Siadat SD, Oloomi M (2017) Designing novel construction for cell surface display of protein E on Escherichia coli using non-classical pathway based on Lpp-OmpA. AMB Express 7(1). https://doi.org/10.1186/s13568-017-0350-0
- Nega M, Dube L, Kull M, Ziebandt AK, Ebner P, Albrecht D, Krismer B, Rosenstein R, Hecker M, Gotz F (2015) Secretome analysis revealed adaptive and non-adaptive responses of the Staphylococcus carnosus femB mutant. Proteomics 15(7):1268–1279. https://doi.org/10.1002/pmic.201400343 CrossRefPubMedPubMedCentralGoogle Scholar
- Oliveira L, Madureira P, Andrade EB, Bouaboud A, Morello E, Ferreira P, Poyart C, Trieu-Cuot P, Dramsi S (2012) Group B streptococcus GAPDH is released upon cell lysis, associates with bacterial surface, and induces apoptosis in murine macrophages. PLoS One 7(1):e29963. https://doi.org/10.1371/journal.pone.0029963 CrossRefPubMedPubMedCentralGoogle Scholar
- Pacheco LG, Slade SE, Seyffert N, Santos AR, Castro TL, Silva WM, Santos AV, Santos SG, Farias LM, Carvalho MA, Pimenta AM, Meyer R, Silva A, Scrivens JH, Oliveira SC, Miyoshi A, Dowson CG, Azevedo V (2011) A combined approach for comparative exoproteome analysis of Corynebacterium pseudotuberculosis. BMC Microbiol 11(1):12. https://doi.org/10.1186/1471-2180-11-12 CrossRefPubMedPubMedCentralGoogle Scholar
- Pasztor L, Ziebandt AK, Nega M, Schlag M, Haase S, Franz-Wachtel M, Madlung J, Nordheim A, Heinrichs DE, Gotz F (2010) Staphylococcal major autolysin (Atl) is involved in excretion of cytoplasmic proteins. J Biol Chem 285(47):36794–36803. https://doi.org/10.1074/jbc.M110.167312 CrossRefPubMedPubMedCentralGoogle Scholar
- Rinas U, Hoffmann F, Betiku E, Estape D, Marten S (2007) Inclusion body anatomy and functioning of chaperone-mediated in vivo inclusion body disassembly during high-level recombinant protein production in Escherichia coli. J Biotechnol 127(2):244–257. https://doi.org/10.1016/j.jbiotec.2006.07.004 CrossRefPubMedGoogle Scholar
- Rosenkrands I, Slayden RA, Crawford J, Aagaard C, Barry CEI, Andersen P (2002) Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins. J Bacteriol 184(13):3485–3491. https://doi.org/10.1128/jb.184.13.3485-3491.2002 CrossRefPubMedPubMedCentralGoogle Scholar
- Scott JR, Barnett TC (2006) Surface proteins of gram-positive bacteria and how they get there. Annu Rev Microbiol 60:397–423. https://doi.org/10.1146/annurev.micro.60.080805.142256 CrossRefPubMedGoogle Scholar
- Tjalsma H, Antelmann H, Jongbloed JD, Braun PG, Darmon E, Dorenbos R, Dubois JY, Westers H, Zanen G, Quax WJ, Kuipers OP, Bron S, Hecker M, van Dijl JM (2004) Proteomics of protein secretion by Bacillus subtilis: separating the “secrets” of the secretome. Microbiol Mol Biol Rev 68(2):207–233. https://doi.org/10.1128/MMBR.68.2.207-233.2004 CrossRefPubMedPubMedCentralGoogle Scholar
- Tullius MV, Harth G, Horwitz MA (2001) High extracellular levels of Mycobacterium tuberculosis glutamine synthetase and superoxide dismutase in actively growing cultures are due to high expression and extracellular stability rather than to a protein-specific export mechanism. Infect Immun 69(10):6348–6363. https://doi.org/10.1128/IAI.69.10.6348-6363.2001 CrossRefPubMedPubMedCentralGoogle Scholar
- Wickner W, Driessen AJ, Hartl FU (1991) The enzymology of protein translocation across the Escherichia coli plasma membrane. Annu Rev Biochem 60:101–124. https://doi.org/10.1146/annurev.bi.60.070191.000533 CrossRefPubMedGoogle Scholar
- Wild K, Bange G, Motiejunas D, Kribelbauer J, Hendricks A, Segnitz B, Wade RC, Sinning I (2016) Structural basis for conserved regulation and adaptation of the signal recognition particle targeting complex. J Mol Biol 428(14):2880–2897. https://doi.org/10.1016/j.jmb.2016.05.015 CrossRefPubMedGoogle Scholar
- Yang CK, Zhang XZ, Lu CD, Tai PC (2014) An internal hydrophobic helical domain of Bacillus subtilis enolase is essential but not sufficient as a non-cleavable signal for its secretion. Biochem Biophys Res Commun 446(4):901–905. https://doi.org/10.1016/j.bbrc.2014.03.032 CrossRefPubMedPubMedCentralGoogle Scholar