DrsG from Streptococcus dysgalactiae subsp. equisimilis inhibits the antimicrobial peptide LL-37

Smyth, D. , Cameron, A., Davies, M. R., McNeilly, C., Hafner, L., Sriprakash, K. S. and McMillan, D. J. (2014) DrsG from Streptococcus dysgalactiae subsp. equisimilis inhibits the antimicrobial peptide LL-37. Infection and Immunity, 82(6), pp. 2337-2344. (doi: 10.1128/IAI.01411-13) (PMID:24664506) (PMCID:PMC4019180)

Abstract

SIC and DRS are related proteins present in only 4 of the >200 Streptococcus pyogenes emm types. These proteins inhibit complement-mediated lysis and/or the activity of certain antimicrobial peptides (AMPs). A gene encoding a homologue of these proteins, herein called DrsG, has been identified in the related bacterium Streptococcus dysgalactiae subsp. equisimilis. Here we show that geographically dispersed isolates representing 14 of 50 emm types examined possess variants of drsG. However, not all isolates within the drsG-positive emm types possess the gene. Sequence comparisons also revealed a high degree of conservation in different S. dysgalactiae subsp. equisimilis emm types. To examine the biological activity of DrsG, recombinant versions of two major DrsG variants, DrsGS and DrsGL, were expressed and purified. Western blot analysis using antisera raised to these proteins demonstrated both variants to be expressed and secreted into culture supernatants. Unlike SIC, but similar to DRS, DrsG does not inhibit complement-mediated lysis. However, like both SIC and DRS, DrsG is a ligand of the cathelicidin LL-37 and is inhibitory to its bactericidal activity in in vitro assays. Conservation of prolines in the C-terminal region also suggests that these residues are important in the biology of this family of proteins. This is the first report demonstrating the activity of an AMP-inhibitory protein in S. dysgalactiae subsp. equisimilis and suggests that inhibition of AMP activity is the primary function of this family of proteins. The acquisition of the complement-inhibitory activity of SIC may reflect its continuing evolution.

• Item Type: Articles
• Additional Information: This work was supported by funding provided by the National Health and Medical Research Council of Australia, the Australian Infectious Diseases Research Centre, and the University of the Sunshine Coast. The ongoing S. dysgalactiae subsp. equisimilis genome sequencing project is supported by The Wellcome Trust, United Kingdom.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smyth, Dr Danielle
• Authors: Smyth, D., Cameron, A., Davies, M. R., McNeilly, C., Hafner, L., Sriprakash, K. S., and McMillan, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Infection and Immunity
• Publisher: American Society for Microbiology
• ISSN: 0019-9567
• ISSN (Online): 1098-5522
• Published Online: 24 March 2014