The Cell Walls of Group D Streptococci

Bleiweis, Arnold S.; Krause, Richard M.

doi:10.1084/jem.122.2.237

Cited by 39 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, only limited information is available on the specific role of polysaccharide antigens in the pathogenicity of enterococcal infections (1,2,13,39,40). CP antigens and teichoic acids from enterococci have been identified and partially characterized by a number of investigators in the past (3,4,9,(25)(26)(27), but the host immune response to these antigens and their potential usefulness as vaccines have not previously been elucidated. Only one attempt at a systematic seroepidemiologic approach to classifying enterococci based on CP structures has been reported (33,34).…”

Section: Discussionmentioning

confidence: 99%

Prophylactic and Therapeutic Efficacy of Antibodies to a Capsular Polysaccharide Shared among Vancomycin-Sensitive and -Resistant Enterococci

et al. 2000

View full text Add to dashboard Cite

Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics, including vancomycin. A recently described capsular polysaccharide (CP) isolated from Enterococcus faecalis 12030 was used to evaluate the potential efficacy of active or passive immunotherapy regimens as adjunctive treatments. Evaluation of protective efficacy was carried out in immunocompetent mice challenged intravenously (i.v.) with live enterococci. In nonimmune mice, i.v. inoculations resulted in high levels of bacteria in kidneys, spleens, and livers 5 days after challenge. Mice immunized with four 10-g doses of CP antigen/mouse were protected against challenge with the homologous E. faecalis strain. High-titer opsonic immunoglobulin G was also induced by immunizing rabbits with the purified CP, and passive transfer of this antiserum to mice produced significantly lower bacterial counts in organs than did normal rabbit serum or sterile saline. Antibodies to the polysaccharide isolated from E. faecalis 12030 were protective against Enterococcus faecalis OG1RF and against two serologically related, vancomycin-resistant Enterococcus faecium clinical isolates. Antibodies to this CP antigen were also effective as a therapeutic reagent in mice when passive therapy was initiated 48 h after live bacterial challenge. These data indicate that CP antigens from enterococci are potential targets of protective antibodies and that these antibodies may be useful for prophylaxis and treatment of enterococcal infections.Enterococcal infections are an increasing threat in modern medicine and especially in intensive care unit (ICU) patients and immunocompromised patients such as neonates, oncology patients, and transplant recipients. In some medical ICUs, enterococci are the second most common bloodstream isolate, more common even than Staphylococcus aureus (31). The National Nosocomial Infection Surveillance System reported in 1998 that Enterococcus spp. were responsible for 10% of bloodstream infections, 14% of urinary tract infections, and 20% of cardiovascular infections in coronary care units (23).The increasing occurrence of multidrug-resistant enterococcal infections, including vancomycin-resistant strains, has resulted in some cases of infection that are difficult to treat with routinely used antimicrobials. Current rates of about 14 to 25% vancomycin resistance in enterococcal isolates in ICUs raise the prospect of a "postantibiotic era" of untreatable bacterial infections (7,8,24). Recently, we identified an enterococcal surface antigen that is a target of opsonic killing (13), a hallmark of antibodies protective against bacterial pathogens (5). Purification and chemical characterization of this antigen revealed a glycerol-teichoic acid-like molecule with a backbone structure of -6-alpha-D-glucose-1-2-glycerol-3-PO 4 -substituted on carbon 2 of the glucose molecule with an alpha-2-1-linked molecule of -D-glucose (38). The purified antigen was immunogenic in rabbits, and th...

show abstract

Section: Discussionmentioning

confidence: 99%

Prophylactic and Therapeutic Efficacy of Antibodies to a Capsular Polysaccharide Shared among Vancomycin-Sensitive and -Resistant Enterococci

et al. 2000

View full text Add to dashboard Cite

show abstract

“…However, we were not able to detect the PS antigen in several E. faecalis strains. Early studies of E. faecalis showed that some cell wall PS were antigenic and might be used for serological typing (1,9,19,21). Neither the chemical compositions nor the genetic basis of these PS have been elucidated.…”

mentioning

confidence: 99%

Analysis of a Gene Cluster ofEnterococcus faecalisInvolved in Polysaccharide Biosynthesis

et al. 2000

View full text Add to dashboard Cite

Previously, we described a gene cluster of Enterococcus faecalis OG1RF that produced an antigenic polysaccharide when cloned in Escherichia coli. The polysaccharide antigen was not detectable in E. faecalis strains, however. Here, we show by reverse transcriptase-PCR that the 16 genes in this region are transcribed in OG1RF. Gene disruption of orfde4, encoding a putative glycosyl transferase, and orfde6, a putative dTDPrhamnose biosynthesis gene, generated two OG1RF mutants. The mutants showed delayed killing and a higher 50% lethal dose in a mouse peritonitis model. In addition, two mucoid E. faecalis isolates from patients with chronic urinary tract infections were found to produce the polysaccharide antigen.Polysaccharides (PS) of bacterial pathogens play important roles during infection. The capsule of Streptococcus pneumoniae is considered its most important virulence factor, since it enables the organism to persist in the host by conferring resistance to phagocytosis (6,8). Capsular PS from Staphylococcus aureus types 5 and 8 were shown to induce cytokine release from human epithelial and endothelial cell lines (22). The serotype f PS (a rhamnose-glucose polymer) of Streptococcus mutans was found to stimulate the release of tumor necrosis factor ␣ (23). Furthermore, being the dominant immunogens on the bacterial surface, some PS (e.g., the O antigens of gram-negative bacteria and capsules of streptococci and staphylococci) have been used as the basis for both vaccine development and serological typing of clinical isolates.Enterococci are a leading cause of nosocomial infections and account for 5 to 15% of infective endocarditis in the United States (14), with most clinical isolates being Enterococcus faecalis. The development of multiple antibiotic resistance in enterococci in recent decades has posed a serious threat to effective therapy and raises awareness of the need for a better understanding of the pathogenicity of enterococci. Members of our group previously reported that a cloned gene cluster (epa, encoding proteins involved in the biosynthesis of an enterococcal PS antigen) of E. faecalis OG1RF produced a PS in Escherichia coli (27). The PS reacted with sera from four patients with enterococcal endocarditis. Sequence analysis showed that epa genes were similar to those involved in the biosynthesis and export of PS, including genes for rhamnose biosynthesis, glycosyl transferases, and ATP-binding cassette transporters. Insertion mutations in three of the genes, orfde4, orfde5, and orfde8, abolished immunoreactivity of the E. coli clone (27). However, we were not able to detect the PS antigen in several E. faecalis strains. Early studies of E. faecalis showed that some cell wall PS were antigenic and might be used for serological typing (1,9,19,21). Neither the chemical compositions nor the genetic basis of these PS have been elucidated. In addition, Bottone et al. (2) recently described the first isolation of mucoid E. faecalis strains from patients with chronic urinary tract infections.The biosynt...

show abstract

“…There is very little information available on cell surface-associated polysaccharides of enterococci. Crude cell wall extracts from E. faecalis type 1 strains performed in the 1960s were found to contain L -rhamnose, glucose, galactose, N-acetylglucosamine and N-acetylgalactosamine [34]. More recently, a carbohydrate polymer was identified containing L -rhamnose, glucosamine, galactosamine, glucose, galactose, and phosphate in a 4:2:2:1:1:1 ratio [35].…”

Section: Discussionmentioning

confidence: 99%

Boosted Rat Natural Xenoantibodies Cross-React with <b><i>Enterococcus faecalis</i></b> by Targeting Melibiose and <smlcap>L</smlcap>-Rhamnose

2013

View full text Add to dashboard Cite

Natural antibodies include a subset described as xenoantibodies considered to be directed at microorganisms and also cross-react with antigens of unrelated species. In this study, we generated T-cell-independent (TI) and T-cell-dependent (TD) xenoantibodies in Lewis rats with hamster and pig blood injections. TI anti-hamster and anti-pig IgM and IgG xenoantibodies cross-reacted with Enterococcus faecalis but not with Escherichia coli isolated from the blood of Lewis rats after cecal ligation and puncture (CLP). TI anti-pig IgM xenoantibodies also showed some reactivity with two human blood isolates of E. faecalis. In contrast, TD xenoantibodies did not show any reactivity with rat or human bacteria. TI and TD anti-hamster and anti-pig IgM and IgG xenoantibodies showed cross-reactivity with lymphocytes and endothelial cells from species distinct to that used for immunization. Glycan array analysis and inhibition assays identified antibodies against melibiose and L-rhamnose as mediators of anti-hamster and anti-porcine xenoantibody cross-reactivity with E. faecalis. A rise in TI anti-hamster and anti-pig xenoantibodies was accompanied by decreased survival of Lewis rats in a low-severity sepsis model of CLP. Therefore, TI xenoantibodies in the rat include anti-carbohydrate antibodies reactive to bacteria of endogenous flora. Enhancement of these antibodies may result in more severe infectious diseases caused by these microorganisms.

show abstract

The Cell Walls of Group D Streptococci

Cited by 39 publications

References 13 publications

Prophylactic and Therapeutic Efficacy of Antibodies to a Capsular Polysaccharide Shared among Vancomycin-Sensitive and -Resistant Enterococci

Prophylactic and Therapeutic Efficacy of Antibodies to a Capsular Polysaccharide Shared among Vancomycin-Sensitive and -Resistant Enterococci

Analysis of a Gene Cluster ofEnterococcus faecalisInvolved in Polysaccharide Biosynthesis

Boosted Rat Natural Xenoantibodies Cross-React with <b><i>Enterococcus faecalis</i></b> by Targeting Melibiose and <smlcap>L</smlcap>-Rhamnose

Contact Info

Product

Resources

About