Mn ²⁺ -Dependent Regulation of Multiple Genes in Streptococcus pneumoniae through PsaR and the Resultant Impact on Virulence

Abstract

The concentration of Mn 2؉ is 1,000-fold higher in secretions than it is at internal sites of the body, making it a potential signal by which bacteria can sense a shift from a mucosal environment to a more invasive site. PsaR, a metal-dependent regulator in Streptococcus pneumoniae, was found to negatively affect the transcription of psaBCA, pcpA, rrgA, rrgB, rrgC, srtBCD, and rlrA in the presence of Mn 2؉ . psaBCA encode an ABC-type transporter for Mn 2؉ . pcpA, rrgA, rrgB, and rrgC encode several outer surface proteins. srtBCD encode a cluster of sortase enzymes, and rlrA encodes a transcriptional regulator. Steady-state RNA levels are high under low Mn 2؉ concentrations in the wild-type strain and are elevated under both high and low Mn

Characterization of a Ferrous Iron-Responsive Two-Component System in Nontypeable Haemophilus influenzae

“…The procedures previously described by Johnston et al were used to evaluate the lung colonization profiles of the H. influenzae strains in C57BL/6 mice (Harlan Laboratories, Indianapolis, IN) (45). Briefly, mice were anesthetized with isoflurane then infected intranasally with 10 7 bacteria in a 50-l volume.…”

At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

“…MntR represses the transcription of mntABC when the intracellular concentrations of Mn are elevated by binding as a homodimer to a 19-bp MntR-box consensus sequence (3). Mn-responsive DtxR homologs have been identified in several gram-positive bacteria including S. pneumoniae (PsaR), Streptococcus gordonii (ScaR), Enterococcus faecalis (EfaR), and Bacillus anthracis (AntR) (105,109,140,203). Although the degree to which mutants of these dtxR homologs have been characterized varies, all were identified as regulating Mn transport, and the S. gordonii and S. pneumoniae homologs have been implicated as being important for virulence.…”

Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

“…To study the contribution of PcpA, PhtD, and PhtABD proteins to adherence to human lung epithelial cells, TIGR4 and its isogenic mutants, the TIGR4⌬PcpA insertion-duplication mutant (19), TIGR4⌬PhtD, and a TIGR4⌬PhtABD triple mutant (9), were incubated with A549 cells for 1 h. The adherence of wild-type TIGR4 to A549 cells was set as maximal adherence (100%), and the reduction in adherence of the mutants compared to that of TIGR4 is shown as percentage adherence compared to that of the wild type (Fig. 1).…”

“…The pcpA gene has been shown to be conserved among 25 different strains examined (18), and PcpA protein is surface exposed (18). PcpA is not required for NP colonization of the mouse (18,19) but is indispensable for murine lung infection (20). PcpA is under the control of a manganese (Mn)-dependent regulator, PsaR, and the Mn concentration in the NP of mice has been shown to result in downregulation of pcpA expression (19).…”

“…PcpA is not required for NP colonization of the mouse (18,19) but is indispensable for murine lung infection (20). PcpA is under the control of a manganese (Mn)-dependent regulator, PsaR, and the Mn concentration in the NP of mice has been shown to result in downregulation of pcpA expression (19). The antibody response elicited by recombinant PcpA vaccination has been shown to provide protection against systemic infection (18) but not against colonization (21) in mice.…”