TY - JOUR
T1 - Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia
AU - Lee, Seungyeop
AU - Ghosh, Prachetash
AU - Kwon, Hyogyoung
AU - Park, Sang Sang
AU - Kim, Gyu Lee
AU - Choi, Sang Yoon
AU - Kim, Eun Hye
AU - Tran, Thao Dang Hien
AU - Seon, Seung Han
AU - Le, Nhat Tu
AU - Iqbal, Hamid
AU - Lee, Sangho
AU - Pyo, Suhkneung
AU - Rhee, Dong Kwon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea [2015R1 A2 A1 A10052511].
Funding Information:
This work was supported by the National Research Foundation (NRF-2015R1 A2 A1 A10052511) to DKR. The funding body played no role in designing the study, data collection and analysis, decision to publish, or manuscript preparation.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Streptococcus pneumoniae (pneumococcus), the major pathogen for pneumonia, commonly colonizes the lung, but the mechanism underlying the coordination of virulence factors during invasion via the host protein remains poorly understood. Bacterial lysis releases the components of the cell wall, and triggers innate immunity and the subsequent secretion of pro-inflammatory cytokines. Previously, the virulence of the pep27 mutant was shown to be attenuated as a feasible candidate for vaccine development. However, the role of pep27 gene, belonging to the vancomycin- resistance locus (vncRS operon), in virulence, is largely unknown. This study demonstrates that transferrin in the host serum reduces the survival of the host during S. pneumoniae infections in mice. The exposure of the pneumococcal D39 strain to lactoferrin induced the vncRS operon, lysis, and subsequent in vivo cytokine production, resulting in lung inflammation. However, these responses were significantly attenuated in pneumococci harboring a mutation in pep27. Mechanistically, the VncS ligand, identified as lactoferrin, induced the vncRS operon and increased the in vivo mortality rates. Thus, serum-induced activation of vncRS plays an essential role in inducing pneumonia.
AB - Streptococcus pneumoniae (pneumococcus), the major pathogen for pneumonia, commonly colonizes the lung, but the mechanism underlying the coordination of virulence factors during invasion via the host protein remains poorly understood. Bacterial lysis releases the components of the cell wall, and triggers innate immunity and the subsequent secretion of pro-inflammatory cytokines. Previously, the virulence of the pep27 mutant was shown to be attenuated as a feasible candidate for vaccine development. However, the role of pep27 gene, belonging to the vancomycin- resistance locus (vncRS operon), in virulence, is largely unknown. This study demonstrates that transferrin in the host serum reduces the survival of the host during S. pneumoniae infections in mice. The exposure of the pneumococcal D39 strain to lactoferrin induced the vncRS operon, lysis, and subsequent in vivo cytokine production, resulting in lung inflammation. However, these responses were significantly attenuated in pneumococci harboring a mutation in pep27. Mechanistically, the VncS ligand, identified as lactoferrin, induced the vncRS operon and increased the in vivo mortality rates. Thus, serum-induced activation of vncRS plays an essential role in inducing pneumonia.
KW - Lactoferrin
KW - Pep27
KW - Pneumococcal pneumonia
KW - Streptococcus pneumoniae
KW - Vncrs
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U2 - 10.1080/21505594.2018.1526529
DO - 10.1080/21505594.2018.1526529
M3 - Article
C2 - 30246592
AN - SCOPUS:85054426693
SN - 2150-5594
VL - 9
SP - 1562
EP - 1575
JO - Virulence
JF - Virulence
IS - 1
ER -