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Short- and Long-Term Effects of Pneumococcal Conjugate Vaccination of Children on Penicillin Resistance. L. Temime, 2004.Recent observations have shown that wide-scale vaccination with pneumococcal conjugate vaccines was associated with a reduction in invasive disease, supporting the expectation that vaccination could help reduce carriage of Streptococcus pneumoniae and control the spread of resistant strains . However, it is too early to assess whether these effects can be sustained in the long term . Here, we used mathematical modeling to investigate time changes in pneumococcal colonization and resistance induced by conjugate vaccination in an environment where antibiotic exposure is high and resistance is widespread . According to model predictions, vaccination induced a decrease in carriage of vaccine-type pneumococci to very low levels, typically in 10 to 15 years under epidemiologically realistic conditions . Almost simultaneously, non-vaccine-type pneumococci spread in the community . Consequently, while there was a short-term decrease in the overall carriage rate, it was followed after a few years by a renewed, although limited, increase . Vaccination with a heptavalent vaccine did not affect the extent to which antibiotic resistance was selected: in all cases, the distribution of resistance levels peaked at high levels (MIC > 2 µg/ml) after 20 years . With a vaccine optimally designed to include all serotypes currently exhibiting decreased susceptibility to penicillin G, the selection of resistance was slowed down, although not prevented . These results suggest that because of serotype replacement, the effects of vaccination observed today may not be sustained in the long term . As a consequence, vaccination alone may not be successful in controlling selection for resistance in S . pneumoniae . Characterization of the Streptomyces sp . Strain C5 snp Locus and Development of snp-Derived Expression Vectors. Charles L. DeSanti, 2003.The Streptomyces sp . strain C5 snp locus is comprised of two divergently oriented genes: snpA, a metalloproteinase gene, and snpR, which encodes a LysR-like activator of snpA transcription . The transcriptional start point of snpR is immediately downstream of a strong T-N11-A inverted repeat motif likely to be the SnpR binding site, while the snpA transcriptional start site overlaps the ATG start codon, generating a leaderless snpA transcript . By using the aphII reporter gene of pIJ486 as a reporter, the plasmid-borne snpR-activated snpA promoter was ca . 60-fold more active than either the nonactivated snpA promoter or the melC1 promoter of pIJ702 . The snpR-activated snpA promoter produced reporter protein levels comparable to those of the up-mutated ermE* promoter . The SnpR-activated snpA promoter was built into a set of transcriptional and translational fusion expression vectors which have been used for the intracellular expression of numerous daunomycin biosynthesis pathway genes from Streptomyces sp . strain C5 as well as the expression and secretion of soluble recombinant human endostatin .
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