Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

Prachetash Ghosh, Hyogyoung Kwon, Sang-Sang Park, Gyu-Lee Kim, Sang-Yoon Choi, Eun-Hye Kim, Thao Dang-Hien Tran, Seung Han Seon, Nhat Tu Le, Hamid Iqbal, Sangho Lee, Suhkneung Pyo, Dong-Kwon Rhee

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1562-1575
Number of pages14
Issue number1
StatePublished - 2018


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