Biomedical subjects

Bernard Beall

Publications and source records attributed to Bernard Beall.

53 records · Page 3Linked to original sources

PubMed2003

M protein gene type distribution among group A streptococcal clinical isolates recovered in Mexico City, Mexico, from 1991 to 2000, and Durango, Mexico, from 1998 to 1999: overlap with type distribution within the United States.

To examine the type distribution of pathogenic group A streptococcal (GAS) strains in Mexico, we determined the emm types of 423 GAS isolates collected from ill patients residing in Mexico (Durango or Mexico City). These included 282 throat isolates and 107 isolates from normally sterile sites. Of the other isolates, 38 were recovered from other miscellaneous infections. A total of 31 different emm types were found, revealing a broad overlap between commonly occurring emm types in Mexico and the United States. The information obtained in this study is consistent with the possibility that multivalent, M type-specific vaccines prepared for GAS strain distribution within the United States could theoretically protect against the majority of GAS strains causing disease in the two cities surveyed in Mexico.

Alleles↗

PubMed2003

Clonal distribution of invasive pneumococcal isolates from children and selected adults in the United States prior to 7-valent conjugate vaccine introduction.

Theseven-valent pneumococcal conjugated polysaccharide vaccine PC7V was licensed for use among children in 2000. Since 90 serotypes of pneumococci exist, an increase in nonvaccine serotypes could occur through immune selection for capsular type switching. Eleven hundred sixty-eight invasive isolates (24 serotypes), recovered primarily from pediatric patients (855 isolates = 73%) and 22 reference strains of known multilocus sequence types (STs) were subjected to macrorestriction profiling (pulsed-field gel electrophoresis [PFGE]). The correlation of 187 ST results (including 49 newly discovered STs) with the PFGE data assigned 1,042 (89.2%) study isolates to 46 defined clonal complexes or genetic lineages based on related multilocus STs (BURST). Seventeen clonal complexes were represented by 2 to 10 related allelic profiles (STs), while 33 lineages (including reference strains) consisted of single STs with 4 or fewer allelic identities to other STs found in the study. Expansion of the BURST analysis to a global analysis of all known pneumococcal STs (as of 27 November 2002) reduced the number of single ST lineages from 33 to 8, and the number of multi-ST clonal complexes was reduced from 17 to 13. In this work, we established the basic genetic structure within individual serotypes prior to PC7V use. The resultant database will be useful for detecting potential selective effects of this vaccine in postvaccine surveillance.

Adult↗

PubMed2002

Population-based surveillance for postpartum invasive group a streptococcus infections, 1995-2000.

Estimates of disease burden and data on the sources of invasive postpartum group A streptococcus (GAS) infections will help guide public health action. Active, population-based surveillance was conducted in 9 regions from 1995 through 2000. A case of GAS infection was defined as isolation of GAS from a sterile site in a resident of a surveillance area who was pregnant or in the postpartum period. Census and live birth data were used to calculate rates. Eighty-seven cases of postpartum GAS infection (2.2% of 3957 invasive GAS infections) occurred at 3%-8% of hospitals annually. We estimate that 220 cases occurred annually in the United States. Two or more cases were noted during 6 months at 8 hospitals, during 1 year at 13 hospitals, and during 2 years at 16 hospitals. Cases due to identical emm types clustered more frequently than expected by chance. Although postpartum GAS infections are rare, the clustering of infections due to identical strains suggests that some invasive cases may have a common source and, therefore, may be preventable.

Adolescent↗

PubMed2002

Epidemiology of invasive group a streptococcus disease in the United States, 1995-1999.

Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10-20 years. We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992). From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons). Rates varied by age (higher among those <2 or >/=65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period. The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates. Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death. We estimate that 9600-9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100-1300 deaths.

Antigens, Bacterial↗

PubMed2002

A novel, multiple drug-resistant, serotype 24F strain of Streptococcus pneumoniae that caused meningitis in patients in Naples, Italy.

Three adult patients in Naples, Italy, had meningitis due to multiple drug-resistant serotype 24F Streptococcus pneumoniae isolates. The 3 isolates were genetically indistinguishable and shared pbp2b and pspA sequence types with previously characterized penicillin-resistant clones. This serotype 24F strain was found to be the same clonal type as a previously characterized, penicillin-resistant serotype 14 strain. The novel strain has probably arisen through transformation of a serotype 14 strain with type 24F capsular biosynthetic operon sequences.

Aged↗

PubMed2002

Emergence of a novel penicillin-nonsusceptible, invasive serotype 35B clone of Streptococcus pneumoniae within the United States.

Monitoring antibiotic-resistant pneumococcal strains not covered by the 7-valent conjugate vaccine is an important priority. The Centers for Disease Control and Prevention's Active Bacterial Core Surveillance identified 68 invasive penicillin-nonsusceptible serotype 35B (PN35B) isolates recovered from 1995 to 2001 from patients residing in the states of California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New York, Oregon, Tennessee, and Texas. Nonsusceptible isolates accounted for 69% of all serotype 35B isolates recovered during this time. Twelve (18%) of the 68 PN35B isolates recovered since 1995 were obtained from pediatric patients. These 68 isolates exhibited penicillin MICs of 0.25-2 microg/mL and reduced susceptibility to cefotaxime. Representative PN35B isolates exhibited a common chromosomal macrorestriction profile and identical penicillin-binding-protein gene restriction profiles characteristic of penicillin-resistant strains, and they shared a unique 7-locus sequence type that included 3 new alleles. The mosaic pbp2b and divergent ddl sequences were suggestive of interspecies recombination at the ddl-pbp2b chromosomal region.

Adolescent↗

PubMed2002

The heterogeneity of endemic community pediatric group a streptococcal pharyngeal isolates and their relationship to invasive isolates.

By use of molecular techniques, the genetic heterogeneity of 63 community pediatric pharyngeal group A streptococcal (GAS) isolates circulating within a 3-week period were compared with 17 contemporaneous invasive pediatric isolates. Pharyngitis isolates represented 16 pulsed-field gel electrophoresis (PFGE) patterns with 12 emm serotypes, and invasive isolates represented 10 PFGE patterns with 9 emm serotypes. One-fourth of the pharyngeal isolates (16/63) were identical to at least 1 invasive isolate; conversely, 10 (59%) of 17 invasive isolates were identical to at least 1 pharyngeal strain. sic allele analysis of emm1 strains demonstrated additional heterogeneity and overlap. More pharyngeal (71%) than invasive isolates (35%) were positive for both speA and speC (P<.02). Many pharyngitis GAS strains circulate simultaneously. Most invasive pediatric GAS strains are identical to acute pharyngitis strains; thus, childhood pharyngitis is a major reservoir for strains with invasive potential. Pharyngeal isolates were more likely to be speA and speC positive than were the invasive isolates.

Adolescent↗

PubMed2002

Streptolysin S and necrotising infections produced by group G streptococcus.

BACKGROUND: We encountered three patients with severe necrotising soft tissue infections due to beta-haemolytic group G streptococcus. Due to strong clinical similarities with invasive infections produced by group A streptococcus, we investigated a potential link of shared beta-haemolytic phenotype to disease pathogenesis. METHODS: Hybridisation, DNA sequencing, targeted mutagenesis, and complementation studies were used to establish the genetic basis for group G streptococcus beta-haemolytic activity. The requirement of group G streptococcus beta-haemolysin in producing necrotising infection was examined in mice. FINDINGS: Each patient had an underlying medical condition. beta-haemolytic group G streptococcus was the sole microbial isolate from debrided necrotic tissue. The group G streptococcus chromosome contained a homologue of the nine-gene group A streptococcus sag operon encoding the beta-haemolysin streptolysin S (SLS). Targeted mutagenesis of the putative SLS structural gene sagA in group G streptococcus eliminated beta-haemolytic activity. Mice injected subcutaneously with wild-type group A streptococcus or group G streptococcus developed an inflammatory lesion with high bacterial counts, marked neutrophil infiltration, and histopathological evidence of diffuse tissue necrosis. These changes were not found in mice injected with the isogenic group A streptococcus or group G streptococcus SLS-negative mutants. INTERPRETATION: In patients with underlying medical conditions, beta-haemolytic group G streptococcus can produce necrotising soft tissue infections resembling those produced by group A streptococcus. The beta-haemolytic phenotype of group G streptococcus is produced by the exotoxin SLS, encoded by a functional homologue of the nine-gene group A streptococcus sag operon. SLS expression contributes to the pathogenesis of streptococcal necrotising soft tissue infection.

Animals↗

PubMed2002

Late-onset group B streptococcal infection in identical twins: insight to disease pathogenesis.

Late-onset group B streptococcal (GBS) infection affecting identical twins is described. Although exhibiting similar signs and symptoms at presentation, twin A suffered fulminant fatal meningitis while twin B recovered completely. The GBS isolates proved to be genetically identical and possessed equivalent abilities to invade and injure cells of the human blood-brain barrier in vitro. Clinical variables associated with the adverse outcome in twin A were longer duration of fever prior to antibiotics and the development of neutropenia. The case histories and experimental data are reviewed to underscore key features of GBS disease pathogenesis.

Age of Onset↗

PubMed2002

Erythromycin-resistant pharyngeal isolates of Streptococcus pyogenes recovered in Italy.

Three classes of macrolide resistance phenotypes and three different erythromycin resistance determinants were found among 127 erythromycin-resistant group A streptococcal (GAS) isolates recovered from 355 (35.8%) pediatric pharyngitis patients in Rome, Italy. According to emm and sof sequence typing results, erythromycin-resistant isolates comprised 11 different clonal types. Remarkably, 126 of the 127 macrolide-resistant isolates were serum opacity factor (sof) gene positive. These data suggest a strong association between macrolide resistance and the presence of sof among GAS isolates recovered from Italian pediatric pharyngitis patients.

Child↗

PubMed2002

Immunogenicity of a 26-valent group A streptococcal vaccine.

A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 microg of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.

Animals↗

PubMed2002

Genotypes of invasive pneumococcal isolates recently recovered from Italian patients.

We examined 73 recent invasive pneumococcal isolates within selected areas of Italy for genotypic variability. Thirty-three genomic macrorestriction types were found, three of which represented multiple serotypes. Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types. Of the nine macrorestriction types found among the 22 penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates, seven comprised isolates with allelic profiles showing five to seven allelic matches to profiles in the multilocus sequence typing database (www.mlst.net); however, three of the seven profiles represented serotypes not previously associated with these clonal clusters. Two PNSP macrorestriction types represented new clones with unique allelic profiles. Allelic profiles obtained from isolates of 3 of the 25 macrorestriction types found among the 51 penicillin-susceptible S. pneumoniae (PSSP) isolates were closely related to previously described profiles. One PSSP isolate was a novel type 24F isolate related to the multiresistant clone France(9V)-3. This work reports new PNSP strains and new serotype-clone associations.

Aminoacyltransferases↗

PubMed2002

Erythromycin-resistant group A streptococcal isolates recovered in Sofia, Bulgaria, from 1995 to 2001.

The frequency of erythromycin resistance within group A streptococci in Sofia, Bulgaria, from 1995 to 2001 was 2.1% (26 isolates). Of this, 57.7% was macrolide-lincosamide-streptogramin (MLS) inducible, 7.7% was MLS constitutive, and 34.6% had the M phenotype. Eleven different emm sequence types were found among 25 erythromycin-resistant isolates tested. Nineteen of 26 erythromycin-resistant isolates were additionally resistant to tetracycline and/or chloramphenicol.

Bulgaria↗

PubMed2001

Extension of the Lancefield classification for group A streptococci by addition of 22 new M protein gene sequence types from clinical isolates: emm103 to emm124.

Classic M protein serotyping has been invaluable during the past 60 years for the determination of relationships between different group A streptococci (GAS) strains and the varied clinical manifestations inflicted by these organisms worldwide. Nonetheless, during the past 20 years, the difficulties of continued expansion of the serology-based Lancefield classification scheme for GAS have become increasingly apparent. By use of a less demanding sequence-based methodology that closely adheres to previously established strain criteria while being predictive of known M protein serotypes, we recently added types emm94-emm102 to the Lancefield scheme. Continued expansion by the addition of types emm103 to emm124 are now proposed. As with types emm94-emm102, each of these new emm types was represented by multiple independent isolates recovered from serious disease manifestations, each was M protein nontypeable with all typing sera stocks available to international GAS reference laboratories, and each demonstrated antiphagocytic properties in vitro by multiplying in normal human blood.

Antigens, Bacterial↗

PubMed2000

emm and sof gene sequence variation in relation to serological typing of opacity-factor-positive group A streptococci.

Approximately 40-60% of group A streptococcal (GAS) isolates are capable of opacifying sera, due to the expression of the sof (serum opacity factor) gene. The emm (M protein gene) and sof 5' sequences were obtained from a diverse set of GAS reference strains and clinical isolates, and correlated with M serotyping and anti-opacity-factor testing results. Attempts to amplify sof from strains with M serotypes or emm types historically associated with the opacity-factor-negative phenotype were negative, except for emm12 strains, which were found to contain a highly conserved sof sequence. There was a strong correlation of certain M serotypes with specific emm sequences regardless of strain background, and likewise a strong association of specific anti-opacity-factor (AOF) types to sof gene sequence types. In several examples, M type identity, or partial identity shared between strains with differing emm types, was correlated with short, highly conserved 5' emm sequences likely to encode M-type-specific epitopes. Additionally, each of three pairs of historically distinct M type reference strains found to share the same 5' emm sequence, were also found to share M serotype specificity. Based upon sof sequence comparisons between strains of the same and of differing AOF types, an approximately 450 residue domain was determined likely to contain key epitopes required for AOF type specificity. Analysis of two Sof sequences that were not highly homologous, yet shared a common AOF type, further implicated a 107 aa portion of this 450-residue domain in putatively containing AOF-specific epitopes. Taken together, the serological data suggest that AOF-specific epitopes for all Sof proteins may reside within a region corresponding to this 107-residue sequence. The presence of specific, hypervariable emm/sof pairs within multiple isolates appears likely to be a reliable indicator of their overall genetic relatedness, and to be very useful for accurate subtyping of GAS isolates by an approach that has relevance to decades of past M-type-based epidemiological data.

Agglutination Tests↗

PubMed1999

Disruption of tonB in Bordetella bronchiseptica and Bordetella pertussis prevents utilization of ferric siderophores, haemin and haemoglobin as iron sources.

The Bordetella bronchiseptica tonB gene was cloned by detection of a chromosomal restriction fragment hybridizing with each of two degenerate oligonucleotides that corresponded to Pro-Glu and Pro-Lys repeats characteristic of known TonB proteins. The tonB(Bb) gene was situated upstream of exbB and exbD homologues and downstream of a putative Fur-regulated promoter. Hybridization results indicated that the tonB operon and flanking regions were highly conserved between B. bronchiseptica, Bordetella pertussis and Bordetella parapertussis. Disruption of tonB in B. bronchiseptica resulted in inability to grow in iron-limiting media, and inability to utilize alcaligin, enterobactin, ferrichrome, desferroxamine B, haemin and haemoglobin. Although it was not possible to inactivate tonB in a clinical B. pertussis isolate, tonB was disrupted in a laboratory B. pertussis strain previously selected for the ability to grow on Luria-Bertani medium. This B. pertussis tonB mutant shared a similar iron complex utilization deficient phenotype with the B. bronchiseptica tonB mutant. The B. bronchiseptica tonB operon present on a plasmid did not complement an Escherichia coli tonB mutant, but inefficient reconstitution of enterobactin utilization was observed in one fepA mutant harbouring plasmid copies of the B. pertussis fepA homologue and tonB(Bb) operon.

Anti-Bacterial Agents↗

PubMed1997

An iron-regulated outer-membrane protein specific to Bordetella bronchiseptica and homologous to ferric siderophore receptors.

The bfrA (Bordetella bronchiseptica ferric iron repressed outer-membrane protein) gene was cloned from Bordetella bronchiseptica by screening a library of TnphoA insertion mutants for iron-repressed fusions to phoA. The bfrA gene encoded an 80 kDa outer-membrane protein with a high level of amino acid sequence identity to several bacterial proteins belonging to the family of Ton B-dependent outer-membrane receptors. BfrA was especially homologous to Cir of Escherichia coli, IrgA of Vibrio cholerae and to three previously characterized ferric enterobactin receptors. DNA hybridization results indicated that bfrA was not present in other Bordetella species. Expression of the bfrA gene was induced by low iron availability from a promoter overlapped by a sequence resembling a consensus Fur-binding sequence, and bfrA expression was derepressed in a B. bronchiseptica fur mutant. Utilization of the Bordetella siderophore alcaligin and the exogenous siderophore enterobactin was unaffected in bfrA mutants. Upon attempting to find the specificity of BfrA, 2,3-dihydroxybenzoylserine (DHBS) was shown to be utilized in a bfeA (Bordetella ferric enterobactin receptor gene)-dependent manner by B. bronchiseptica and B. pertussis. In addition, the hydroxamate siderophores ferrichrome and desferrioxamine B, and the iron source haemin were shown to be utilized independently of bfeA and bfrA in B. bronchiseptica and B. pertussis.

Amino Acid Sequence↗