Variability of Penicillin-Binding Proteins from Penicillin-Sensitive Streptococcus pneumoniae

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

doi:10.1093/infdis/164.2.307

Cited by 34 publications

(24 citation statements)

References 22 publications

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“…To test for the expression of PcpA in all of the strains, they were grown in low-manganese medium (Յ0.1 M) (19,25). Total cellular protein samples were prepared from mid-logphase cells cultured in the low-manganese medium.…”

Section: Resultsmentioning

confidence: 99%

Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

Glover¹,

Hollingshead²,

Briles

2008

Infect Immun

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Previous studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence of Streptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewer S. pneumoniae cells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4-to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.

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Section: Resultsmentioning

confidence: 99%

Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

Glover¹,

Hollingshead²,

Briles

2008

Infect Immun

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“…Six of these had been observed previously, but the remaining four were novel and are not contained with the database that already contains 97 pbp2X RFLP patterns. This demonstrates the highly variable nature of the pbp2X gene, suggesting that it undergoes more recombination or that point mutations occur more frequently than in either of the other pbp genes (14). Variations in the RFLP patterns of the pbp2X gene only were responsible for six of the seven distinct genotypes observed among the PSP isolates.…”

Section: Vol 41 2003 Invasive Pneumococci In the Republic Of Irelanmentioning

confidence: 90%

Penicillin Susceptibility and Epidemiological Typing of Invasive Pneumococcal Isolates in the Republic of Ireland

et al. 2003

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A national study was undertaken to investigate the incidence of invasive pneumococcal disease in the Republic of Ireland and to examine the associated isolates. In 1999, 144 S. pneumoniae isolates, all recovered from cases of invasive disease, were received from 12 microbiology laboratories. The incidence of invasive pneumococcal disease was estimated to be 6.6/100,000 population. All isolates were analyzed for serotype, penicillin susceptibility, chromosomal relatedness (by using pulsed-field gel electrophoresis [PFGE]), and penicillin-binding protein (pbp) fingerprinting. Several findings of note were observed regarding the pneumococcal population in Ireland. First, isolates of 25 different serotypes were represented, with serotypes 14, 9V, 8, 5, 4, and 3 being the most common. This finding, together with the pbp fingerprinting and PFGE typing results, indicated the clonal spread of strains of these serotypes in Ireland. Second, 27 (18.7%) isolates had reduced susceptibility to penicillin, and 74% of these were serotype 9V. Of these, 80% appeared to belong to the same clone. This could suggest the spread of the international Spanish/French 9V penicillin-resistant clone into Ireland. Third, nine different pbp genotypes were identified, four of which were new. Two pbp genotypes accounted for the majority of isolates dividing them according to their penicillin susceptibility status but irrespective of serotype and PFGE type. This is strong evidence for the occurrence of horizontal transfer of pbp genes between strains, observed with both penicillin-susceptible and penicillin-nonsusceptible isolates. Fourth, there was evidence of serotype transformation since isolates, indistinguishable by pbp fingerprinting and PFGE typing, expressed different capsular types.

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“…An example that could be exploited for diagnosing antibiotic resistance is the pbp2x gene, which must be present in all strains, since it is an essential gene (13). In fact, all penicillinresistant strains were recognized here on the basis of sequence variation in their pbp2x gene, making this gene a tool suitable for diagnostic chip design (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…(i) Penicillin resistance. PBP2x represents a primary resistance determinant, and all penicillin-resistant isolates contain a low-affinity PBP2x encoded by a mosaic pbp2x gene, due to localized interspecies recombinational events (13,23). Figure 3a shows the intensity ratios between KNR.7/87 and all 20 strains for PBP2x.…”

Section: Downloaded Frommentioning

confidence: 99%

Mosaic Genes and Mosaic Chromosomes: Intra- and Interspecies Genomic Variation of Streptococcus pneumoniae

et al. 2001

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Streptococcus pneumoniae remains a major causative agent of serious human diseases. The worldwide increase of antibiotic resistant strains revealed the importance of horizontal gene transfer in this pathogen, a scenario that results in the modulation of the species-specific gene pool. We investigated genomic variation in 20 S. pneumoniae isolates representing major antibiotic-resistant clones and 10 different capsular serotypes. Variation was scored as decreased hybridization signals visualized on a high-density oligonucleotide array representing 1,968 genes of the type 4 reference strain KNR.7/87. Up to 10% of the genes appeared altered between individual isolates and the reference strain; variability within clones was below 2.1%. Ten gene clusters covering 160 kb account for half of the variable genes. Most of them are associated with transposases and are assumed to be part of a flexible gene pool within the bacterial population; other variable loci include mosaic genes encoding antibiotic resistance determinants and gene clusters related to bacteriocin production. Genomic comparison between S. pneumoniae and commensal Streptococcus mitis and Streptococcus oralis strains indicates distinct antigenic profiles and suggests a smooth transition between these species, supporting the validity of the microarray system as an epidemiological and diagnostic tool.

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Variability of Penicillin-Binding Proteins from Penicillin-Sensitive Streptococcus pneumoniae

Cited by 34 publications

References 22 publications

Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

Penicillin Susceptibility and Epidemiological Typing of Invasive Pneumococcal Isolates in the Republic of Ireland

Mosaic Genes and Mosaic Chromosomes: Intra- and Interspecies Genomic Variation of Streptococcus pneumoniae

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