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1.
Pathog Dis ; 76(7)2018 10 01.
Article in English | MEDLINE | ID: mdl-30215741

ABSTRACT

Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has developed a wide range of virulence factors to evade the immune system of which the polysaccharide capsule is the most important one. Formation of this capsule is dependent on the cps gene locus, but also involves other genes-like galU. The pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of prokaryotes and is required for the biosynthesis of capsular polysaccharides. In this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence using a Galleria mellonella model has been studied. We show that the mutation improves streptococcal adherence to epithelial cells and macrophage phagocytosis in vitro, while there is no definitive correlation on biofilm formation between parent and mutant strains. Moreover, in vivo virulence is attenuated for all mutated strains. Together, these results demonstrate that a galU mutation in S. pneumoniae influences host cell interactions in vitro and in vivo and can strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is worth investigating further as a potential drug target.


Subject(s)
Bacterial Adhesion , Biofilms/growth & development , Mutant Proteins/genetics , Mutation , Phagocytosis , Streptococcus pneumoniae/enzymology , UTP-Glucose-1-Phosphate Uridylyltransferase/genetics , Animals , Bacterial Capsules/metabolism , Cell Line , Disease Models, Animal , Epithelial Cells/microbiology , Humans , Lepidoptera , Macrophages/immunology , Macrophages/microbiology , Mice , Mutant Proteins/metabolism , Pneumococcal Infections/microbiology , Pneumococcal Infections/pathology , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/immunology , Streptococcus pneumoniae/physiology , UTP-Glucose-1-Phosphate Uridylyltransferase/metabolism , Virulence Factors/genetics , Virulence Factors/metabolism
4.
Int J Antimicrob Agents ; 25(3): 260-3, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15737523

ABSTRACT

Streptococcus pneumoniae isolates (n = 262) were recovered from adult patients with community-acquired pneumonia. Erythromycin-resistance levels increased from 9% (1997-1998) to 16% (2000-2002). Sampling for resistance mechanisms prevalent within 19 erythromycin-resistant S. pneumoniae showed mef(E) in 13/19 isolates while 4/19 carried the erm(B) gene (3/19 cMLS(B) and 1/19 iMLS(B) phenotype). MIC ranges for erythromycin and clindamycin were 0.5-16 mg/l and <0.008-0.063 mg/l for the M phenotype, 128-512 mg/l and 128-256 mg/l for the cMLS(B) phenotype, and 4 and <0.008 mg/l for the iMLS(B) phenotype. This is the first report studying the prevalence of macrolide resistance determinants in S. pneumoniae in our country.


Subject(s)
Anti-Bacterial Agents/pharmacology , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial/genetics , Macrolides/pharmacology , Pneumonia, Pneumococcal/microbiology , Streptococcus pneumoniae/drug effects , Adult , Argentina , Bacterial Proteins/genetics , Clindamycin/pharmacology , Erythromycin/pharmacology , Genes, Bacterial , Genotype , Hospitals, Teaching , Humans , Membrane Proteins/genetics , Methyltransferases/genetics , Microbial Sensitivity Tests , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/isolation & purification
5.
Epidemiol Infect ; 132(2): 177-84, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15061491

ABSTRACT

PspA is an antigenically variable virulence factor of Streptococcus pneumoniae that inhibits complement deposition and is a potential candidate for human vaccines. Of 64 published strains 96% are in PspA families 1 and 2; optimal protection is family-specific. Effective development of a PspA-containing vaccine requires more information about the PspA family of strains in parts of the world where the vaccine is most needed. In these studies we observed that of 149 isolates (of 19 capsular types) from Argentina, 54.4% were family 1, 41.6% were family 2 and 4.0% expressed both family 1 and family 2 PspAs. Box typing revealed the Argentinian strains to be from at least 10 clonally related groups.


Subject(s)
Bacterial Proteins/genetics , Streptococcus pneumoniae/classification , Child , Child, Preschool , Genetic Variation , Humans , Infant , Infant, Newborn , Serotyping , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/immunology
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