Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation

Cuong Thach Nguyen; Nhat-Tu Le; Thao Dang-Hien Tran; Eun-Hye Kim; Sang-Sang Park; Truc Thanh Luong; Kyung-Tae Chung; Suhkneung Pyo; Dong-Kwon Rhee

doi:10.1128/IAI.02012-14

Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation

Cuong Thach Nguyen, Nhat-Tu Le, Thao Dang-Hien Tran, Eun-Hye Kim, Sang-Sang Park, Truc Thanh Luong, Kyung-Tae Chung, Suhkneung Pyo, Dong-Kwon Rhee

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

Original language	English (US)
Pages (from-to)	3802-10
Number of pages	9
Journal	Infection and Immunity
Volume	82
Issue number	9
DOIs	https://doi.org/10.1128/IAI.02012-14
State	Published - Sep 2014

Keywords

Actin Depolymerizing Factors
Actins
Bacterial Adhesion
Bacterial Proteins
Cell Line, Tumor
Endopeptidase Clp
Humans
Lung Neoplasms
Pneumococcal Infections
Serine Endopeptidases
Streptococcus pneumoniae
Telomere-Binding Proteins
Virulence
rac1 GTP-Binding Protein
Journal Article
Research Support, Non-U.S. Gov't

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10.1128/IAI.02012-14

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title = "Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation",

abstract = "Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.",

keywords = "Actin Depolymerizing Factors, Actins, Bacterial Adhesion, Bacterial Proteins, Cell Line, Tumor, Endopeptidase Clp, Humans, Lung Neoplasms, Pneumococcal Infections, Serine Endopeptidases, Streptococcus pneumoniae, Telomere-Binding Proteins, Virulence, rac1 GTP-Binding Protein, Journal Article, Research Support, Non-U.S. Gov't",

author = "Nguyen, {Cuong Thach} and Nhat-Tu Le and Tran, {Thao Dang-Hien} and Eun-Hye Kim and Sang-Sang Park and Luong, {Truc Thanh} and Kyung-Tae Chung and Suhkneung Pyo and Dong-Kwon Rhee",

year = "2014",

month = sep,

doi = "10.1128/IAI.02012-14",

language = "English (US)",

volume = "82",

pages = "3802--10",

journal = "Infection and Immunity",

issn = "0019-9567",

publisher = "American Society for Microbiology",

number = "9",

}

TY - JOUR

T1 - Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation

AU - Nguyen, Cuong Thach

AU - Le, Nhat-Tu

AU - Tran, Thao Dang-Hien

AU - Kim, Eun-Hye

AU - Park, Sang-Sang

AU - Luong, Truc Thanh

AU - Chung, Kyung-Tae

AU - Pyo, Suhkneung

AU - Rhee, Dong-Kwon

PY - 2014/9

Y1 - 2014/9

N2 - Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

AB - Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

KW - Actin Depolymerizing Factors

KW - Actins

KW - Bacterial Adhesion

KW - Bacterial Proteins

KW - Cell Line, Tumor

KW - Endopeptidase Clp

KW - Humans

KW - Lung Neoplasms

KW - Pneumococcal Infections

KW - Serine Endopeptidases

KW - Streptococcus pneumoniae

KW - Telomere-Binding Proteins

KW - Virulence

KW - rac1 GTP-Binding Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1128/IAI.02012-14

DO - 10.1128/IAI.02012-14

M3 - Article

C2 - 24980975

SN - 0019-9567

VL - 82

SP - 3802

EP - 3810

JO - Infection and Immunity

JF - Infection and Immunity

IS - 9

ER -

Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation

Abstract

Keywords

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