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. 2005 Dec;187(24):8340-9.
doi: 10.1128/JB.187.24.8340-8349.2005.

Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae

Ramkumar Iyer  1 , Nitin S Baliga, Andrew Camilli
Affiliations

V体育平台登录 - Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae

Ramkumar Iyer et al. J Bacteriol. 2005 Dec.

Abstract

We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible beta-galactosidase activity in S. pneumoniae. CCR of maltose-inducible alpha-glucosidase, raffinose-inducible alpha-galactosidase, and cellobiose-inducible beta-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these systems. The ccpA strain is severely attenuated for nasopharyngeal colonization and lung infection in the mouse, establishing its role in fitness on these mucosal surfaces VSports手机版. Comparison of the cell wall fraction of the ccpA and wild-type strains shows that CcpA regulates many proteins in this compartment that are involved in central and intermediary metabolism, a subset of which are required for survival and multiplication in vivo. Both in vitro and in vivo defects were complemented by providing ccpA in trans. Our results demonstrate that CcpA, though not a global regulator of CCR in S. pneumoniae, is required for colonization of the nasopharynx and survival and multiplication in the lung. .

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Figures

FIG. 1.
FIG. 1.
CCR of sugar-degrading enzymes in S. pneumoniae. (A) β-Galactosidase activity in wild-type and ccpA and bgaA mutant cells in the presence of the inducer lactose (L) alone compared to activity in the presence of the repressing sugar glucose (L+G) or sucrose (L+S). (B) β-Glucosidase activity in wild-type and ccpA mutant cells in the presence of the inducer cellobiose (C) compared to activity in the presence of the repressing sugar glucose (C+G). (C) α-Galactosidase activity in wild-type and ccpA mutant cells in the presence of the inducer raffinose (R) alone compared to activity in the presence of the repressing sugar sucrose (R+S). (D) α-Glucosidase activity in wild-type and ccpA mutant cells in the presence of the inducer maltose (M) alone compared to activity in the presence of the repressing sugar sucrose (M+S).
FIG. 2.
FIG. 2.
Role of ccpA in pneumonia and nasopharyngeal colonization in mice. Loss of ccpA causes attenuation of the ccpA mutant (ccpA) in an in vivo competition with the wild type in the pneumonia (Lung) and nasopharyngeal carriage (N.P.) models of infection. Provision of a single copy of ccpA complements both defects (ΔccpA/ccpA+). Horizontal bars represent geometric means.
FIG. 3.
FIG. 3.
Single-strain pneumonia and nasopharyngeal colonization of mice with the wild type and the ccpA mutant. The ccpA strain (ccpA) is attenuated in both pneumonia (A) and nasopharyngeal colonization (B) compared to the wild type. Open symbols represent data at or below the limit of detection (∼100 per mouse). Horizontal bars represent arithmetic means.
FIG. 4.
FIG. 4.
2-D gels of cell wall fraction of S. pneumoniae. Panels: A, wild type; B, ccpA mutant (ccpA)−; C, ccpA-complemented strain (ΔccpA/ccpA+). Arrows indicate differences in the protein profiles. M.W., molecular mass.
FIG. 5.
FIG. 5.
RPA to analyze mRNA levels of SP1176 (ptsI) (A) and SP1128 (enolase) (B) in wild-type (Wt) strain AC353 and ccpA strain RI1932. Riboprobes for SP1176 (ptsI), SP1128 (enolase), and SP1414 (rpsU loading control) were generated and hybridized to 3 μg of RNA from the three S. pneumoniae strains. RNA was harvested from cells grown in THB to an OD600 of 0.3. Undigested riboprobes of SP1176, SP1414, and SP1128 in the absence of S. pneumoniae RNA are indicated. An rpoB riboprobe is also indicated but was not used in the experiments. The value below a lane is the relative abundance of the SP1176 or SP1128 transcript in the wild-type or ccpA strain normalized to SP1414 (rpsU), as calculated by densitometry with ImageQuant TL software (Amersham Biosciences).
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References

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