RESUMO
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.
Assuntos
Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Proteínas Mutantes/genética , Mutação , Fagocitose , Streptococcus pneumoniae/enzimologia , UTP-Glucose-1-Fosfato Uridililtransferase/genética , Animais , Cápsulas Bacterianas/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/microbiologia , Humanos , Lepidópteros , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Proteínas Mutantes/metabolismo , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/fisiologia , UTP-Glucose-1-Fosfato Uridililtransferase/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismoAssuntos
Farmacorresistência Bacteriana/genética , Lincosamidas/metabolismo , Nucleotidiltransferases/genética , Streptococcus agalactiae/genética , Proteínas de Bactérias/genética , Clindamicina/farmacologia , Eritromicina/farmacologia , Feminino , Humanos , Lincosamidas/farmacologia , Dados de Sequência Molecular , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificaçãoRESUMO
Here, we describe the first case of a Streptococcus lutetiensis isolate harboring the lnuB gene.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/diagnóstico , Clindamicina/farmacologia , Farmacorresistência Bacteriana , Genes Bacterianos , Streptococcus/isolamento & purificação , Idoso , Bacteriemia/microbiologia , DNA Bacteriano/química , DNA Bacteriano/genética , Humanos , Masculino , Dados de Sequência Molecular , Análise de Sequência de DNA , Streptococcus/efeitos dos fármacos , Streptococcus/genéticaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Adulto , Argentina , Proteínas de Bactérias/genética , Clindamicina/farmacologia , Eritromicina/farmacologia , Genes Bacterianos , Genótipo , Hospitais de Ensino , Humanos , Proteínas de Membrana/genética , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
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.
