Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus

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Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. / Logsdon, Lauren K; Håkansson, Anders P; Wessels, Michael R; Cortés, Guadalupe.

In: mBio, Vol. 2, No. 1, 2011, p. e00332-10.

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Logsdon, Lauren K ; Håkansson, Anders P ; Wessels, Michael R ; Cortés, Guadalupe. / Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. In: mBio. 2011 ; Vol. 2, No. 1. pp. e00332-10.

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TY - JOUR

T1 - Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus

AU - Logsdon, Lauren K

AU - Håkansson, Anders P

AU - Wessels, Michael R

AU - Cortés, Guadalupe

N1 - Copyright © 2011 Logsdon et al.

PY - 2011

Y1 - 2011

N2 - Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.

AB - Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.

KW - Bacterial Proteins

KW - Cell Line

KW - Clathrin

KW - Down-Regulation

KW - Dynamins

KW - Gene Expression Regulation, Bacterial

KW - Humans

KW - Keratinocytes

KW - Streptococcal Infections

KW - Streptococcus pyogenes

KW - Streptolysins

U2 - 10.1128/mBio.00332-10

DO - 10.1128/mBio.00332-10

M3 - Article

C2 - 21325037

VL - 2

SP - e00332-10

JO - mBio

JF - mBio

SN - 2161-2129

IS - 1

ER -