title: Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae.
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. 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.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Iyer
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D050260:Carbohydrate Metabolism; D002353:Carrier State / Q000382:microbiology; D002473:Cell Wall / Q000737:chemistry; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D007785:Lactose / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000382:microbiology; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors; D000519:alpha-Galactosidase / Q000032:analysis; D000520:alpha-Glucosidases / Q000032:analysis; D001616:beta-Galactosidase / Q000032:analysis; D001617:beta-Glucosidase / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012097:Repressor Proteins; D037521:Virulence Factors; C069286:catabolite control proteins, bacteria; D000520:alpha-Glucosidases; D001617:beta-Glucosidase; D000519:alpha-Galactosidase; D001616:beta-Galactosidase; D007785:Lactose