Subversion of phagocytosis Overall strategies, continued Survival inside phagocytes Escape into the cytoplasm Inhibition of lysosome and phagosome fusion Resistance to lysosomal enzymes Inhibition of phagocyte oxidative pathway Antibody effects(host counters) BIOL 533 Lecture 8
BIOL 533 12 Lecture 8 Subversion of Phagocytosis • Overall strategies, continued – Survival inside phagocytes • Escape into the cytoplasm • Inhibition of lysosome and phagosome fusion • Resistance to lysosomal enzymes • Inhibition of phagocyte oxidative pathway – Antibody effects (host counters)
Subversion of phagocytosis General aspects Being inside cell is not necessarily bad for an organism Powerful strategy is to grow within nonphagocytic cell Shielded from antibodies and drugs BIOL 533 Lecture 8
BIOL 533 13 Lecture 8 Subversion of Phagocytosis • General aspects – Being inside cell is not necessarily bad for an organism • Powerful strategy is to grow within nonphagocytic cell – Shielded from antibodies and drugs
Subversion of phagocytosis Inhibition of phagocyte recruitment Direct inhibition of neutrophil motility and chemotaxis o Bordetella pertussis produces toxins Adenylate cyclase toxin > Increase cyclic AMP in neutrophils >> Leads to paralysis Pertussis toxin >>Impairs migration of monocytes BIOL 533 Lecture 8
BIOL 533 14 Lecture 8 Subversion of Phagocytosis • Inhibition of phagocyte recruitment – Direct inhibition of neutrophil motility and chemotaxis • Bordetella pertussis produces toxins – Adenylate cyclase toxin » Increase cyclic AMP in neutrophils » Leads to paralysis – Pertussis toxin » Impairs migration of monocytes
Subversion of phagocytosis Microbial killing of phagocytes Leukocidins(exotoxins) kill neutrophils and macrophages Can work at distance or after ingestion Typical producers are highly invasive bacteria Pseudomonas, staphylococci, group a streptococci, gas gangrene clostridia BIOL 533 Lecture 8
BIOL 533 15 Lecture 8 Subversion of Phagocytosis • Microbial killing of phagocytes – Leukocidins (exotoxins) kill neutrophils and macrophages • Can work at distance or after ingestion • Typical producers are highly invasive bacteria – Pseudomonas, staphylococci, group A streptococci, gas gangrene clostridia
Subversion of phagocytosis Escaping ingestion Naked capsule is effective(pneumococci) Opsonized bacteria not as effective Countering opsonization by complement components or ab Any mechanism inhibits Activation of complement Synthesis or activity of Ab BIOL 533 Lecture 8
BIOL 533 16 Lecture 8 Subversion of Phagocytosis • Escaping ingestion – Naked capsule is effective (pneumococci) • Opsonized bacteria not as effective – Countering opsonization by complement components or Ab • Any mechanism inhibits – Activation of complement – Synthesis or activity of Ab