Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains.

Holger Kneuper,Kate B Twomey,James S Cargill,William N Hunter,Franziska Jäger,James Chalmers,Jan Maarten Van Dijl,Zhen Ping Cao,Tracy Palmer,Robert P Ryan,Martin Zoltner,Magdalena M Van Der Kooi‐Pol

doi:10.1111/mmi.12707

Abstract

The Type VII protein secretion system, found in Gram-positive bacteria, secretes small proteins, containing a conserved W-x-G amino acid sequence motif, to the growth medium. Staphylococcus aureus has a conserved Type VII secretion system, termed Ess, which is dispensable for laboratory growth but required for virulence. In this study we show that there are unexpected differences in the organization of the ess gene cluster between closely related strains of S. aureus. We further show that in laboratory growth medium different strains of S. aureus secrete the EsxA and EsxC substrate proteins at different growth points, and that the Ess system in strain Newman is inactive under these conditions. Systematic deletion analysis in S. aureus RN6390 is consistent with the EsaA, EsaB, EssA, EssB, EssC and EsxA proteins comprising core components of the secretion machinery in this strain. Finally we demonstrate that the Ess secretion machinery of two S. aureus strains, RN6390 and COL, is important for nasal colonization and virulence in the murine lung pneumonia model. Surprisingly, however, the secretion system plays no role in the virulence of strain SA113 under the same conditions.

Highlights

Most bacteria secrete proteins into their external environments, where they play essential roles in nutrient acquisition, colonization and host interactions
We further show that in laboratory growth medium different strains of S. aureus secrete the EsxA and EsxC substrate proteins at different growth points, and that the Ess system in strain Newman is inactive under these conditions
Systematic deletion analysis in S. aureus RN6390 is consistent with the EsaA, EsaB, EssA, EssB, EssC and EsxA proteins comprising core components of the secretion machinery in this strain

Summary

Introduction

Most bacteria secrete proteins into their external environments, where they play essential roles in nutrient acquisition, colonization and host interactions. A secretion system that has, to date, only been experimentally described in Gram-positive bacteria, variously termed the ESX, Ess or Type VII protein secretion system, serves to translocate proteins to the extracellular environment. This secretion system was first described in pathogenic mycobacteria where it secretes two T cell antigens, ESAT-6 (early secreted antigenic target, 6 kDa) and CFP-10 (culture filtrate protein 10 kDa), renamed EsxA and EsxB, respectively, and was shown to be essential for virulence (Hsu et al, 2003; Pym et al, 2003; Stanley et al, 2003). This secretion system has variously been shown to function in other actinobacterial species, Type VII secretion in S. aureus 929 including non-pathogenic members (Abdallah et al, 2006; Akpe San Roman et al, 2010; Fyans et al, 2013)

Results

Discussion

Conclusion