Group A Streptococcal M1 Protein Provides Resistance against the Antimicrobial Activity of Histones

Döhrmann S, LaRock CN, Anderson EL, Cole JN, Ryali B, Stewart C, Nonejuie P, Pogliano J, Corriden R, Ghosh P, Nizet V.

Sci. Rep. 7, 43039

Speaker: Ke-Ying Hsieh (謝可盈)                                Time: 14:00~15:00, May. 31, 2017

Commentator: Dr. I-Hsiu Huang (黃一修老師)           Place: Room 601

Abstract:

Once pathogens are sensed by our immune system, neutrophils will be recruited to the site of infection and eliminate pathogens by phagocytosis or by neutrophil extracellular traps (NETs). NETs are composed of cellular DNA and many antimicrobial peptides secreted from neutrophils ^[1]. 70 % of the proteins secreted in NETs are composed of histones, a group of positively charged proteins that help eukaryotic DNA winding and regulate gene expression. It is known that histones also have antimicrobial activity ^[2], which suggests they might play crucial roles in innate immunity. In this study, the authors first used six representative strains of Gram-positive bacteria to see if histones released from NETs had antimicrobial effect on those bacteria. Among the six Gram-positive bacteria, group A streptococcus (GAS) showed significantly higher resistance to histones compare to others. Next, the authors screened multiple isogenic GAS mutants lacking individual candidate virulence factors and found that emm1 (encoding the surface-anchored M1 protein) mutant strain exhibited decreased histone resistance. Further analysis using flow cytometry revealed that histone binds to GAS via M1. Furthermore, N-terminus region of M1 protein was found to be responsible for histone binding. Expression of M1 protein in the usually histone sensitive Lactococcus lactis also increased its histone resistance. Taken together, the authors discovered a novel strategy for GAS to evade histone killing using its surface proteins and also highlighted the importance of histones in innate immunity.

References:

1.     Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535

2.     Hirsch, J. G. Bactericidal action of histone. J Exp Med. 1958 Dec 1; 108(6):925-44.