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. 2015 Apr 8;6:279.
doi: 10.3389/fmicb.2015.00279. eCollection 2015.

CRH Promotes S. Pneumoniae Growth in Vitro and Increases Lung Carriage in Mice

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Free PMC article

CRH Promotes S. Pneumoniae Growth in Vitro and Increases Lung Carriage in Mice

Colette G Ngo Ndjom et al. Front Microbiol. .
Free PMC article

Abstract

Streptococcus pneumoniae (S. pneumoniae), a commensal across the nasal passages, is responsible for the majority of infectious pneumonia cases worldwide. Previous studies have shown that hormonal factors may be influential in regulating S. pneumoniae's transition from a non-pathogen to a pathogenic state. The current study investigated the effects of corticotropin-releasing hormone (CRH), a peptide hormone involved in stress, on the pathogenicity of S. pneumoniae. Mice were infected with CRH-treated S. pneumoniae via intranasal route, showing an increase in pulmonary bacterial burden. We also quantified S. pneumoniae's response to CRH through limited serial dilutions and growth curve analysis. We demonstrated that CRH promotes S. pneumoniae titer-dependent proliferation, as well as accelerates log-phase growth. Results also showed an increase in pneumococcal-associated virulence protein A virulence gene expression in response to CRH. These results demonstrate a role for CRH in S. pneumoniae pathogenicity, thus implicating CRH in mediating the transition of S. pneumoniae into a pathogenic state.

Keywords: Corticotropin releasing hormone; Streptococcus pneumoniae; commensal; hormones; pathogenicity; respiratory; virulence.

Figures

FIGURE 1
FIGURE 1
Corticotropin-releasing hormone (CRH)-treated Streptococcus pneumoniae increases mice lung carriage. We assessed whether or not exposing mice to S. pneumoniae (105 cells), previously treated or untreated with CRH, would result in bacterial burden for the mice. Mice (N = 5) treated with previously exposed to CRH bacteria (2.0 × 105 cells) showed an increase in lung carriage compared to the unexposed group. Bar graphs represent the mean ± SE of (N = 5) the number of CFUs in lungs. Asterisks () indicate significant (P ≤ 0.05) differences between experimental groups.
FIGURE 2
FIGURE 2
Titer-dependent effects of CRH on S. pneumoniae colony formation. Ten-fold serial dilutions of S. pneumoniae were incubated in the absence (A) or presence of two concentrations of CRH, 2.1 × 10-4 μM (B) and 4.0 × 10-4 μM, (C) and plated on blood agar plates. Data shown is representative of two independent experiments (A). (B) Represents quantitation of the aforementioned results in (A). Bars represent mean (N = 3) ± SE. Asterisks () indicate significant (P ≤ 0.05) differences between experimental groups. White bars denote unexposed S. pneumoniae, gray and black bars denote S. pneumoniae exposed to two different CRH concentrations, 4.0 × 10-4 μM and 2.0 × 10-4 μM, respectively (B). (C) Highlights the specificity of CRH compared to its homolog UCN. Bars represent mean (N = 3) ± SE. Asterisks () indicate significant (P ≤ 0.05) differences between experimental groups.
FIGURE 3
FIGURE 3
Corticotropin-releasing hormone accelerates log-phase growth of S. pneumoniae. S. pneumoniae, CRH exposed (2.1 × 10-4 μM/μl) vs. non-exposed, growth analysis was performed over a period of 9 h. Asterisks () indicate significant (P ≤ 0.05) differences observed in the final bacterial mass during stationary phase. All experiments were performed in duplicates.
FIGURE 4
FIGURE 4
Streptococcus pneumoniae adhesion and virulence factors increase in the presence of CRH. pavA gene expression was determined by quantitative realtime PCR analysis of S. pneumoniae’s mRNA exposed to CRH (N = 3). The analysis showed overexpression of the bacterium’s adhesion and virulence gene (pavA) when compared to control genes. Asterisks () indicate significant (P ≤ 0.05) difference between CRH treated (CRH-Sp) and non-CRH treated (Sp) bacterial groups.

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