Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus sanguinis, a normal inhabitant of the human oral cavity, has low cariogenicity, though colonization on tooth surfaces by this bacterium initiates aggregation by other oral bacteria and maturation of dental plaque. Additionally, S. sanguinis is frequently isolated from infective endocarditis patients. We investigated the functions of sortase A (SrtA), which cleaves LPXTG-containing proteins and anchors them to the bacterial cell wall, as a possible virulence factor of S. sanguinis. We identified the srtA gene of S. sanguinis by searching a homologous gene of Streptococcus mutans in genome databases. Next, we constructed an srtA-deficient mutant strain of S. sanguinis by insertional inactivation and compared it to the wild type strain. In the case of the mutant strain, some surface proteins could not anchor to the cell wall and were partially released into the culture supernatant. Furthermore, adherence to saliva-coated hydroxyapatite beads and polystyrene plates, as well as adherence to and invasion of human epithelial cells were reduced significantly in the srtA-deficient strain when compared to the wild type. In addition, antiopsonization levels and bacterial survival of the srtA-deficient mutant were decreased in human whole blood. This is the first known study to report that SrtA contributes to antiopsonization in streptococci. Our results suggest that SrtA anchors surface adhesins as well as some proteins that function as antiopsonic molecules as a means of evading the human immune system. Furthermore, they demonstrate that SrtA of S. sanguinis plays important roles in bacterial colonization.
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PMID:Role of Streptococcus sanguinis sortase A in bacterial colonization. 1704 3

Surface adhesion plays an essential part in the survival of the commensal organism Streptococcus gordonii in the oral cavity as well as during opportunistic infections such as endocarditis. At least two types of cell surface protein involved in adhesion are found on the surface of Gram-positive bacteria: those anchored via an LPXTG motif by the enzyme sortase A (SrtA) and those associated with the cell surface by, as yet, unknown mechanisms. In srtA(-) mutants, LPXTG-containing proteins have been shown to be released rather than cross-linked to the cell wall. We have therefore used 2D gel electrophoresis of released proteins from an srtA(-) mutant as well as the wild-type strain, followed by peptide identification by MS, to identify a set of novel proteins predicted to be present on the surface of S. gordonii DL1. This includes two large LPXTG-linked proteins (SGO_0707 and SGO_1487), which both contain tandemly repeated sequences similar to those present in known fibrillar adhesins. A 5'-nucleotidase and a protein with a putative collagen-binding domain, both containing LPXTG motifs, were also identified. Anchorless proteins with known chaperone, stress response and elongation factor functions, apparently responsible for bacterial binding to keratinocytes and saliva-coated surfaces in the absence of the LPXTG-linked adhesins, were also associated with the cell surface. These data reveal a range of proteins to be present on the S. gordonii DL1 cell surface, the expression of which plays an important role in adhesion to epithelia and which represent likely candidates for novel virulence factors in S. gordonii.
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PMID:Identification of novel LPXTG-linked surface proteins from Streptococcus gordonii. 1938 83

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified-a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (approximately 2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.
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PMID:Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis. 1970 77

Staphylococcus lugdunensis is a commensal of humans and an opportunistic pathogen. It can cause an aggressive form of infective endocarditis in healthy humans akin to Staphylococcus aureus. Here we compared the virulence of the genome-sequenced S. lugdunensis strain N920143 to S. aureus in an experimental rat endocarditis model. N920143 caused a milder course of disease with lower levels of bacteraemia and smaller endocardial vegetations than S. aureus strain Newman. However, vegetations were comparable to those produced by S. aureus MRSA strain COL. Little is known about virulence factors of S. lugdunensis as systems to manipulate the bacterium genetically are currently limited. Here, we report a method for electroporation of S. lugdunensis with plasmid DNA and demonstrate that the low efficiency of transformation is due to the activity of a conserved type I restriction-modification system. To streamline the transformation process, we constructed SL01B, an E. coli strain expressing the hsdM/hsdS genes of N920143. Modified plasmid DNA isolated from SL01B transformed S. lugdunensis strains from clonal complexes 1 and 2 efficiently. A deletion mutant of N920143 lacking sortase A was significantly less virulent than the wild-type in the endocarditis model. Mutants defective in single surface proteins Fbl or vWbl were not significantly different from the wild-type but showed trends towards reduced virulence.
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PMID:Sortase A promotes virulence in experimental Staphylococcus lugdunensis endocarditis. 2394 87

Streptococcus gallolyticus is an emerging cause of infective endocarditis that has been epidemiologically linked to colorectal cancer. S. gallolyticus is poorly transformable using electroporation and no defined mutant has been published yet. Hence, we used mobilization to introduce plasmid DNA from Streptococcus agalactiae into S. gallolyticus using the transfer origin of the conjugative element TnGBS1 (oriTTnGBS1), followed by a classical homologous recombination technique. Two isogenic mutants of S. gallolyticus UCN34, one deleted for the pil1 pilus operon and another for the sortase A gene, were constructed and characterized. This genetic tool should help in unravelling virulence mechanisms of this bacterium.
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PMID:Construction of isogenic mutants in Streptococcus gallolyticus based on the development of new mobilizable vectors. 2415 86