Cytolysin-dependent evasion of lysosomal killing

Research output: Contribution to journalArticle

Abstract

Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into lysosomes, where they were killed by a pH-dependent mechanism. Because SLO is the prototype of cholesterol-dependent cytolysins produced by many Gram-positive bacteria, cytolysin-mediated evasion of lysosomal killing may be a general mechanism to protect such pathogens from clearance by host epithelial cells.

Details

Authors
External organisations
  • Brigham and Women's Hospital / Harvard Medical School
Research areas and keywords

Keywords

  • Bacterial Proteins, Cells, Cultured, Exocytosis, Genes, Bacterial, Humans, Hydrogen-Ion Concentration, Immunity, Mucosal, Keratinocytes, Lysosomes, Mutation, Oropharynx, Streptococcus pyogenes, Streptolysins, Virulence
Original languageEnglish
Pages (from-to)5192-5197
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume102
Issue number14
Publication statusPublished - 2005 Apr 5
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes