A Serine-Threonine Kinase (StkP) Regulates Expression of the Pneumococcal Pilus and Modulates Bacterial Adherence to Human Epithelial and Endothelial Cells In Vitro.

Jenny A Herbert,Timothy J Mitchell,Andrea M Mitchell,Eliane Namie Miyaji

doi:10.1371/journal.pone.0127212

Jenny A Herbert, Timothy J Mitchell + Show 2 more

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https://doi.org/10.1371/journal.pone.0127212

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Journal: PloS one	Publication Date: Jun 19, 2015
Citations: 17	License type: CC BY 4.0

Affiliation: University of Birmingham

Abstract

The pneumococcal serine threonine protein kinase (StkP) acts as a global regulator in the pneumococcus. Bacterial mutants deficient in StkP are less virulent in animal models of infection. The gene for this regulator is located adjacent to the gene for its cognate phosphatase in the pneumococcal genome. The phosphatase dephosphorylates proteins phosphorylated by StkP and has been shown to regulate a number of key pneumococcal virulence factors and to modulate adherence to eukaryotic cells. The role of StkP in adherence of pneumococci to human cells has not previously been reported. In this study we show StkP represses the pneumococcal pilus, a virulence factor known to be important for bacterial adhesion. In a serotype 4 strain regulation of the pilus by StkP modulates adherence to human brain microvascular endothelial cells (HBMEC) and human lung epithelial cells. This suggests that the pneumococcal pilus may play a role in adherence during infections such as meningitis and pneumonia. We show that regulation of the pilus occurs at the population level as StkP alters the number of pili-positive cells within a single culture. As far as we are aware this is the first gene identified outside of the pilus islet that regulates the biphasic expression of the pilus. These findings suggest StkPs role in cell division may be linked to regulation of expression of a cell surface adhesin.

Highlights

Streptococcus pneumoniae is normally found as a commensal in the nasopharynx of humans, colonising 10% to 40% of adults and children respectively [1]
The full length and allelic variant amino acid sequence of StkP are shown in S1 Fig. Deletion of the whole 3rd protein and serine threonine kinase associated (PASTA) domain in this strain has occurred between two almost identical 10 amino acid repeats located at the end of the second and third PASTA domain
In this study we show that StkP regulates expression of the pneumococcal pilus in TIGR4

Summary

Introduction

Streptococcus pneumoniae is normally found as a commensal in the nasopharynx of humans, colonising 10% to 40% of adults and children respectively [1]. This bacterium can cause a number of invasive diseases including meningitis, septicaemia, pneumonia and otitis media. The organism is the worlds biggest killer of children under the age of five, and is a huge burden on the health services worldwide [2]. There are over 90 different capsule types and only a small proportion of these can be included in the vaccine composition [3]. Vaccine replacement and capsule switching adds to the PLOS ONE | DOI:10.1371/journal.pone.0127212. Vaccine replacement and capsule switching adds to the PLOS ONE | DOI:10.1371/journal.pone.0127212 June 19, 2015

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