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.
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Cuong Thach
authors: CT
authors: Nguyen
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Nhat-Tu
authors: NT
authors: Le
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Thao Dang-Hien
authors: TD
authors: Tran
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Eun-Hye
authors: EH
authors: Kim
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Sang-Sang
authors: SS
authors: Park
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Truc Thanh
authors: TT
authors: Luong
authors: Department of Clinical Laboratory Science, Dong-Eui University, Busan, South Korea.
authors: Kyung-Tae
authors: KT
authors: Chung
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors: Suhkneung
authors: S
authors: Pyo
authors: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea dkrhee@skku.edu.
authors: Dong-Kwon
authors: DK
authors: Rhee
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049071:Endopeptidase Clp; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D001426:Bacterial Proteins; C107953:RAC1 protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D012697:Serine Endopeptidases; C501427:ClpP protein, Streptococcus pneumoniae; D049071:Endopeptidase Clp; D020830:rac1 GTP-Binding Protein