Antigenic Variation of Penicillin-Binding Proteins from Penicillin-Resistant Clinical Strains of Streptococcus pneumoniae

Hakenbeck, Regine; Briese, Thomas; Chalkley, L. J.; Ellerbrok, Heinz; Kalliokoski, Raili; Latorre, Carlota Cesarini; Leinonen, Maija; Martin, Carine

doi:10.1093/infdis/164.2.313

Cited by 72 publications

(29 citation statements)

References 23 publications

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“…Resistance of pneumococci to penicillin occurs when alterations in the organism's PBPs reduce their affinity for ␤-lactam agents (17). The genes encoding the PBPs are mosaics in which sequences of the native (susceptible) pbp genes have been replaced with blocks of highly altered DNA from other pneumococci or streptococcal species (9,29,33).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we used DNA fingerprinting (restriction digestion analysis of PCR products obtained after amplification of distinct regions of the pbp genes) to provide a more discriminating method for differentiating the pbp genes of ␤-lactamresistant pneumococci than SDS-PAGE and fluorography (6,8,17). Previous studies using DNA fingerprinting and sequencing of pbp genes indicated the presence of extensive heterogeneity in natural populations of penicillin-resistant pneumococci, suggesting that resistant strains have arisen independently many times (9,19).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States

McDougal

Rasheed

Biddle

et al. 1995

Antimicrob Agents Chemother

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We characterized 12 isolates of Streptococcus pneumoniae with various levels of susceptibility to penicillin and extended-spectrum cephalosporins by antimicrobial susceptibility patterns, serotypes, ribotypes, chromosomal DNA restriction patterns by pulsed-field gel electrophoresis, multilocus enzyme electrophoresis patterns, penicillin-binding protein (PBP) profiles, and DNA restriction endonuclease cleavage profiles of pbp1a, pbp2x, and pbp2b. Seven cefotaxime-resistant (MIC, >2 g/ml) serotype 23F isolates were related on the basis of ribotyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis, but they had two slightly different PBP patterns: one unique to strains for which the MIC of penicillin is high (4.0 g/ml) and one unique to strains for which the MIC of penicillin is low (0.12 to 1.0 g/ml). The pbp1a and pbp2x fingerprints were identical for the seven isolates; however, the pbp2b fingerprints were different. An eighth serotype 23F isolate with high-level resistance to cephalosporins was not related to the other seven isolates by typing data but was a variant of the widespread, multiresistant serotype 23F Spanish clone. The PBP profiles and fingerprints of pbp1a, pbp2x, and pbp2b were identical to those of the Spanish clone isolate. An additional serotype 6B isolate with high-level resistance to cephalosporins had unique typing profiles and was unrelated to the serotype 23F cephalosporin-resistant isolates but was related on the basis of genetic typing methods to a second serotype 6B isolate that was cephalosporin susceptible. The serotype 6B isolates had different PBP profiles and fingerprints for pbp1a, but the fingerprints for pbp2x and pbp2b were the same.Penicillin-resistant strains of Streptococcus pneumoniae, first isolated in the late 1960s in Australia, are now prevalent throughout the world and are often associated with resistance to other antimicrobial agents (1, 25). In the United States, previous surveys revealed only sporadic occurrences of penicillin-resistant pneumococcal isolates (prevalence, Յ5% [23,46]); however, more recent surveys show much higher rates of infection caused by resistant pneumococci (14,16,47). Although the optimal therapy for infections caused by penicillinintermediate or -resistant strains of pneumococci has not been established, several reports indicate that cefotaxime or ceftriaxone is the drug of choice for initial empiric therapy for meningitis and sepsis caused by this pathogen (7,14,31).Most pneumococcal isolates that are resistant to penicillin also have increased resistance to extended-spectrum cephalosporins, including cefotaxime and ceftriaxone. The MICs of penicillin are generally equal to or two to four times higher than the MICs of the cephalosporins. Recently, we (45) and others (3, 14, 22) reported on infections caused by pneumococcal isolates that have not responded to cephalosporin therapy and for which the MICs of cefotaxime and ceftriaxone are 2 to 32 g/ml. These MICs are in excess of the MICs of penicillin for these isolat...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States

McDougal

Rasheed

Biddle

et al. 1995

Antimicrob Agents Chemother

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“…Pneumococcal strains were grown in synthetic medium (CDM) or in Todd-Hewitt medium containing 0.5% yeast extract (THY) as described previously (70). The study used the serotype 19F strains EF3030 and BG8826 (2), the serogroup 6 strain SP670 (31), the serotype 3 strain WU2 (14), the serotype 2 strain D39 (3), and versions of D39 lacking capsule (44), pneumococcal surface protein C (PspC) (4), pneumococcal surface protein A (PspA) (46), pneumolysin (9), and autolysin (LytA) (8). Pneumococci were verified by their sensitivity to optochin, using a optochin-diffusion assay on blood agar, resulting in a clearing zone around the optochin disc (from Fluka Analytical/SigmaAldrich) of Ͼ15 mm (12).…”

Section: Methodsmentioning

confidence: 99%

Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and Colonization In Vitro and In Vivo

2012

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The human nasopharynx is the main reservoir for Streptococcus pneumoniae (the pneumococcus) and the source for both horizontal spread and transition to infection. Some clinical evidence indicates that nasopharyngeal carriage is harder to eradicate with antibiotics than is pneumococcal invasive disease, which may suggest that colonizing pneumococci exist in biofilm communities that are more resistant to antibiotics. While pneumococcal biofilms have been observed during symptomatic infection, their role in colonization and the role of host factors in this process have been less studied. Here, we show for the first time that pneumococci form highly structured biofilm communities during colonization of the murine nasopharynx that display increased antibiotic resistance. Furthermore, pneumococcal biofilms grown on respiratory epithelial cells exhibited phenotypes similar to those observed during colonization in vivo, whereas abiotic surfaces produced less ordered and more antibiotic-sensitive biofilms. The importance of bacterial-epithelial cell interactions during biofilm formation was shown using both clinical strains with variable colonization efficacies and pneumococcal mutants with impaired colonization characteristics in vivo. In both cases, the ability of strains to form biofilms on epithelial cells directly correlated with their ability to colonize the nasopharynx in vivo, with colonization-deficient strains forming less structured and more antibiotic-sensitive biofilms on epithelial cells, an association that was lost when grown on abiotic surfaces. Thus, these studies emphasize the importance of host-bacterial interactions in pneumococcal biofilm formation and provide the first experimental data to explain the high resistance of pneumococcal colonization to eradication by antibiotics.

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“…The first serotype 9 strain resistant to penicillin was isolated in Spain in 1987 (Hakenbeck etal., 1991). Three other strains belonging to the same serotype were later isolated in the same country (Hakenbeck et al, 1991). They are resistant to similar penicillin concentrations and share the same multilocus enzyme electrophoresis (MLEE) pattern, showing that they had very likely originated from a unique clone (Sibold et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Relatedness of penicillin-resistant Streptococcus pneumoniae serogroup 9 strains from France and Spain

Geslin²,

Am³

1995

Microbiology

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Pulsed-f ield gel electrophoresis of the genomic DNA of penicillin-resistant strains of Streptococcus pneumoniae was carried out. Eleven clinical strains of serogroup 9 from different French towns and Paris hospitals were tested. The restriction enzymes Apal and SmaI were used to digest intact chromosomes, and the fragments were resolved by f ield-inversion gel electrophoresis (FIGE). Five strains were similar using Apal and Smal. Four others were closely related when using Apal, and five others were closely related when using Smal. These results suggest that 10 of these strains are genetically related and have a clonal origin. The profile of the eleventh strain was completely different. Thus, in a given serotype the spreading of penicillin resistance can result from both clonal and independent events. Five strains had similar FIGE profiles to strains first isolated in Spain, suggesting that a resistant strain had spread from Spain to France.

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Antigenic Variation of Penicillin-Binding Proteins from Penicillin-Resistant Clinical Strains of Streptococcus pneumoniae

Cited by 72 publications

References 23 publications

Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States

Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States

Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and Colonization In Vitro and In Vivo

Relatedness of penicillin-resistant Streptococcus pneumoniae serogroup 9 strains from France and Spain

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