Co(2+)-dependent gene expression in Streptococcus pneumoniae: opposite effect of Mn(2+) and Co(2+) on the expression of the virulence genes psaBCA, pcpA, and prtA.

Sulman Shafeeq,Oscar P Kuipers,Irfan Manzoor,Tomas G Kloosterman

doi:10.3389/fmicb.2015.00748

Abstract

Manganese (Mn2+)-, zinc (Zn2+)- and copper (Cu2+) play significant roles in transcriptional gene regulation, physiology, and virulence of Streptococcus pneumoniae. So far, the effect of the important transition metal ion cobalt (Co2+) on gene expression of S. pneumoniae has not yet been explored. Here, we study the impact of Co2+ stress on the transcriptome of S. pneumoniae strain D39. BLAST searches revealed that the genome of S. pneumoniae encodes a putative Co2+-transport operon (cbi operon), the expression of which we show here to be induced by a high Co2+ concentration. Furthermore, we found that Co2+, as has been shown previously for Zn2+, can cause derepression of the genes of the PsaR virulence regulon, encoding the Mn2+-uptake system PsaBCA, the choline binding protein PcpA and the cell-wall associated serine protease PrtA. Interestingly, although Mn2+ represses expression of the PsaR regulon and Co2+ leads to derepression, both metal ions stimulate interaction of PsaR with its target promoters. These data will be discussed in the light of previous studies on similar metal-responsive transcriptional regulators.

Highlights

The Gram-positive bacterium Streptococcus pneumoniae resides asymptomatically in the human nasopharynx (Bogaert et al, 2004)
BLAST searches with the CbiMNQO sequences revealed the presence of putative Co2+-transport genes in S. pneumoniae D39 as well (Supplementary Figure S1)
We have explored Co2+-dependent gene expression in the human pathogen S. pneumoniae by whole transcriptome analysis

Summary

Introduction

The Gram-positive bacterium Streptococcus pneumoniae resides asymptomatically in the human nasopharynx (Bogaert et al, 2004). During its route from the nasopharynx to other parts of the human body, it is exposed to different levels of macro- and micronutrients, including varying concentrations of transition metal ions, which can affect the expression of various genes involved in virulence as well as metabolic processes (Gupta et al, 2009; Shafeeq et al, 2011a, 2013). The interplay of and competition between different metal ions play an important role in the regulation of metal ion homeostasis and physiology in bacteria (Dudev and Lim, 2008; Jacobsen et al., 2011). Co2+ is an important transition metal ion for many bacteria (Nies, 1992) and takes the fourth position in the Irving–Williams stability series, where the order is Mn2+ < Fe2+ < Co2+ < Ni2+ < Cu2+ > Zn2+ (Irving and Williams, 1953).

Methods

Results

Conclusion