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1.
Proc Natl Acad Sci U S A ; 103(8): 2857-62, 2006 Feb 21.
Article in English | MEDLINE | ID: mdl-16481624

ABSTRACT

Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.


Subject(s)
Fimbriae, Bacterial/physiology , Genes, Bacterial/physiology , Genomic Islands , Pneumonia, Bacterial/microbiology , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/pathogenicity , Animals , Bacterial Adhesion/genetics , Bacterial Proteins/genetics , Fimbriae, Bacterial/genetics , Fimbriae, Bacterial/ultrastructure , Genes, Bacterial/genetics , Genomic Islands/genetics , Genomic Islands/physiology , Mice , Mice, Inbred C57BL , Mutation , Respiratory Mucosa/microbiology , Streptococcus pneumoniae/ultrastructure , Trans-Activators/genetics , Virulence
2.
Mol Microbiol ; 39(6): 1452-63, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11260463

ABSTRACT

Production of cellulose has been thought to be restricted to a few bacterial species such as the model organism Acetobacter xylinus. We show by enzymatic analysis and mass spectrometry that, besides thin aggregative fimbriae, the second component of the extracellular matrix of the multicellular morphotype (rdar) of Salmonella typhimurium and Escherichia coli is cellulose. The bcsA, bcsB, bcsZ and bcsC genes responsible for cellulose biosynthesis are not regulated by AgfD, the positive transcriptional regulator of the rdar morphotype. Transcription of the bcs genes was not co-expressed with the rdar morphotype under any of the environmental conditions examined. However, cellulose biosynthesis was turned on by the sole expression of adrA, a gene encoding a putative transmembrane protein regulated by agfD, indicating a novel pathway for the activation of cellulose synthesis. The co-expression of cellulose and thin aggregative fimbriae leads to the formation of a highly hydrophobic network with tightly packed cells aligned in parallel in a rigid matrix. As the production of cellulose would now appear to be a property widely distributed among bacteria, the function of the cellulose polymer in bacteria will have to be considered in a new light.


Subject(s)
Arabidopsis Proteins , Cellulose/metabolism , Escherichia coli/metabolism , Extracellular Matrix/metabolism , Gene Expression Regulation, Bacterial , Salmonella typhimurium/metabolism , Transcription Factors , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli/genetics , Extracellular Matrix/chemistry , Fimbriae, Bacterial/genetics , Genome, Bacterial , Glucosyltransferases/genetics , Glucosyltransferases/metabolism , Multigene Family , Mutation , Salmonella typhimurium/genetics
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