Rials/analysis tools: DX JZ. Wrote the paper: HC HW.

Streptococcus
Rials/analysis tools: DX JZ. Wrote the paper: HC HW.
Streptococcus pneumoniae (the pneumococcus) is a Gram positive bacterium that causes severe invasive infection such as pneumonia, septicemia, and meningitis especially in children, the elderly and immunocompromised patients [1?]. It has been estimated that the pneumococcus is responsible for 14.5 million cases of disease worldwide and more than 800,000 deaths in children under five each year [4]. Colonization of the nasopharynx is a necessary step along the path to pneumococcal disease (PD) [5,6]. Upon entering the nasopharynx, and during its residence there, the pneumococcus shares this anatomical and physiological niche with an array of other bacterial inhabitants [7,8]. Once Title Loaded From File carriage is established in the nasopharynx, the pneumococcus can remain asymptomatic or migrate through the Eustachian tubes to cause otitis media, descend down the respiratory tract to cause pneumonia, or invade the bloodstream through the respiratory epithelium to cause bacteremia or meningitis [6,9]. The mechanism(s) behind this migration, preceding disease, is not fully understood. The prevalence of pneumococcal carriage increases in the first few years of life, peaking at approximately 50?0 in hosts 2?3 years of age and decreasing thereafter until stabilizing at 5?0 in hosts over 10 years 16985061 of age in industrialized countries [5,10?4]. Studies have reported carriage rates as high as 60 in adults from some developing countries [12,15]. Carriage studies have classically utilized bacteriologic cultures, and more recently molecular detection using highly sensitive quantitative PCR (qPCR) reactions. These reactions target selected genes found in most screened S. pneumoniae isolates and genome-sequenced strains, (e.g. lytA, ply or cps4A) [16,17]. To date, at least 93 capsular serotypes have been identified among S. pneumoniae strains [6,18,19]. Prevention of PD in children has been achieved by vaccination with pneumococcal conjugate vaccine (PCV), the basis for which is induction of a protective antibody response against the bacterial polysaccharide capsule [6,20]. Although vaccination has been documented as effective for reducing PD mortality and burden, it seems clear that vaccines with greater coverage, based on proteins (non-capsular antigens) common to all serotypes, will be needed in the future [20]. The ideal protein antigen is one that is present on the cell surface, expressed during nasopharyngeal (NP) carriage and in all stages of the disease (e.g. in lungs during pneumonia) and highly conserved within all serotypes. Animal models of PD and in vitro cultures of human respiratory cells have allowed the identification of a number of factors implicated in colonization of the nasopharynx and in pathogenesis [3,21]. These factors include the capsular polysaccharide, pneumococcal pneumolysin (Ply), adhesins, several proteins implicated in fratricide and regulators. Some of the best characterized candidates as proteinaceousExpression of Sp Genes in the Human NasopharynxTable 1. Primers utilized in this study.Name JVS1L JVS2R JVS5L JVS6R JVS27L JVS28R JVS29L JVS30R JVS31L JVS32R JVS35L JVS36R JVS53L JVS54R JVS55L JVS56R JVS57L JVS58R JVS59L 1676428 JVS60R JVS61L JVS62R JVS63L JVS64R JVS65L JVS66R JVS67L JVS68R JVS69L Title Loaded From File JVS70R JVS73L JVS74R JVS75L JVS76R JVS77L JVS78R JVS79L JVS80R JVS81L JVS82R JVS83L JVS84R 1406F* 23Sr*Target lytASequence (59 to 39) AGTTTAAGCATGATATTGAGAAC TTCGTTGAAATAGTACCACTTATluxSACATCATCTCCAATTATGAT.Streptococcus
Rials/analysis tools: DX JZ. Wrote the paper: HC HW.
Streptococcus pneumoniae (the pneumococcus) is a Gram positive bacterium that causes severe invasive infection such as pneumonia, septicemia, and meningitis especially in children, the elderly and immunocompromised patients [1?]. It has been estimated that the pneumococcus is responsible for 14.5 million cases of disease worldwide and more than 800,000 deaths in children under five each year [4]. Colonization of the nasopharynx is a necessary step along the path to pneumococcal disease (PD) [5,6]. Upon entering the nasopharynx, and during its residence there, the pneumococcus shares this anatomical and physiological niche with an array of other bacterial inhabitants [7,8]. Once carriage is established in the nasopharynx, the pneumococcus can remain asymptomatic or migrate through the Eustachian tubes to cause otitis media, descend down the respiratory tract to cause pneumonia, or invade the bloodstream through the respiratory epithelium to cause bacteremia or meningitis [6,9]. The mechanism(s) behind this migration, preceding disease, is not fully understood. The prevalence of pneumococcal carriage increases in the first few years of life, peaking at approximately 50?0 in hosts 2?3 years of age and decreasing thereafter until stabilizing at 5?0 in hosts over 10 years 16985061 of age in industrialized countries [5,10?4]. Studies have reported carriage rates as high as 60 in adults from some developing countries [12,15]. Carriage studies have classically utilized bacteriologic cultures, and more recently molecular detection using highly sensitive quantitative PCR (qPCR) reactions. These reactions target selected genes found in most screened S. pneumoniae isolates and genome-sequenced strains, (e.g. lytA, ply or cps4A) [16,17]. To date, at least 93 capsular serotypes have been identified among S. pneumoniae strains [6,18,19]. Prevention of PD in children has been achieved by vaccination with pneumococcal conjugate vaccine (PCV), the basis for which is induction of a protective antibody response against the bacterial polysaccharide capsule [6,20]. Although vaccination has been documented as effective for reducing PD mortality and burden, it seems clear that vaccines with greater coverage, based on proteins (non-capsular antigens) common to all serotypes, will be needed in the future [20]. The ideal protein antigen is one that is present on the cell surface, expressed during nasopharyngeal (NP) carriage and in all stages of the disease (e.g. in lungs during pneumonia) and highly conserved within all serotypes. Animal models of PD and in vitro cultures of human respiratory cells have allowed the identification of a number of factors implicated in colonization of the nasopharynx and in pathogenesis [3,21]. These factors include the capsular polysaccharide, pneumococcal pneumolysin (Ply), adhesins, several proteins implicated in fratricide and regulators. Some of the best characterized candidates as proteinaceousExpression of Sp Genes in the Human NasopharynxTable 1. Primers utilized in this study.Name JVS1L JVS2R JVS5L JVS6R JVS27L JVS28R JVS29L JVS30R JVS31L JVS32R JVS35L JVS36R JVS53L JVS54R JVS55L JVS56R JVS57L JVS58R JVS59L 1676428 JVS60R JVS61L JVS62R JVS63L JVS64R JVS65L JVS66R JVS67L JVS68R JVS69L JVS70R JVS73L JVS74R JVS75L JVS76R JVS77L JVS78R JVS79L JVS80R JVS81L JVS82R JVS83L JVS84R 1406F* 23Sr*Target lytASequence (59 to 39) AGTTTAAGCATGATATTGAGAAC TTCGTTGAAATAGTACCACTTATluxSACATCATCTCCAATTATGAT.