Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease

Author:

Burggraaf Maroeska J.1,Speer Alexander2,Meijers Aniek S.2,Ummels Roy2,van der Sar Astrid M.2,Korotkov Konstantin V.3ORCID,Bitter Wilbert24,Kuijl Coenraad2ORCID

Affiliation:

1. Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Microbiology and Infection Control, Cancer Center Amsterdam, Amsterdam, Netherlands

2. Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Microbiology and Infection Control, Amsterdam Institute of Infection & Immunity, Amsterdam, Netherlands

3. Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA

4. Molecular Microbiology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

Abstract

Aspartic proteases are common in eukaryotes and retroviruses but are relatively rare among bacteria (N. D. Rawlings and A. Bateman, BMC Genomics 10:437, 2009, https://doi.org/10.1186/1471-2164-10-437 ). In contrast to eukaryotic aspartic proteases, bacterial aspartic proteases are generally located in the cytoplasm. We have identified a surface-associated mycobacterial aspartic protease, PecA, which cleaves itself and many other type VII secretion substrates of the PE_PGRS family. PecA is present in most pathogenic mycobacterial species, including M. tuberculosis . In addition, pathogenicity of M. marinum is reduced in the ΔpecA mutant, indicating that PecA contributes to virulence.

Funder

Cancer Center Amsterdam

NWO VENI

National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference40 articles.

1. WHO. 2018. Global tuberculosis report 2018. World Health Organization, Geneva, Switzerland.

2. Bottai D, Groschel MI, Brosch R. 2017. Type VII secretion systems in Gram-positive bacteria, p 235–266. In Bagnoli F, Rappuoli R (ed), Protein and sugar export and assembly in Gram-positive bacteria. Springer Nature, Cham, Switzerland.

3. Take five — Type VII secretion systems of Mycobacteria

4. Systematic Genetic Nomenclature for Type VII Secretion Systems

5. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti

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