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1.
Ugeskr Laeger ; 184(43)2022 10 24.
Artigo em Dinamarquês | MEDLINE | ID: mdl-36331171

Assuntos
Mpox , Humanos
2.
Glycobiology ; 31(12): 1655-1669, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34314482

RESUMO

The opportunistic pathogen Streptococcus mitis possesses, like other members of the Mitis group of viridans streptococci, phosphorylcholine (P-Cho)-containing teichoic acids (TAs) in its cell wall. Bioinformatic analyses predicted the presence of TAs that are almost identical with those identified in the pathogen Streptococcus pneumoniae, but a detailed analysis of S. mitis lipoteichoic acid (LTA) was not performed to date. Here, we determined the structures of LTA from two S. mitis strains, the high-level beta-lactam and multiple antibiotic resistant strain B6 and the penicillin-sensitive strain NCTC10712. In agreement with bioinformatic predictions, we found that the structure of one LTA (type IV) was like pneumococcal LTA, except the exchange of a glucose moiety with a galactose within the repeating units. Further genome comparisons suggested that the majority of S. mitis strains should contain the same type IV LTA as S. pneumoniae, providing a more complete understanding of the biosynthesis of these P-Cho-containing TAs in members of the Mitis group of streptococci. Remarkably, we observed besides type IV LTA, an additional polymer belonging to LTA type I in both investigated S. mitis strains. This LTA consists of ß-galactofuranosyl-(1,3)-diacylglycerol as glycolipid anchor and a poly-glycerol-phosphate chain at the O-6 position of the furanosidic galactose. Hence, these bacteria are capable of synthesizing two different LTA polymers, most likely produced by distinct biosynthesis pathways. Our bioinformatics analysis revealed the prevalence of the LTA synthase LtaS, most probably responsible for the second LTA version (type I), among S. mitis and Streptococcus pseudopneumoniae strains.


Assuntos
Streptococcus mitis , Ácidos Teicoicos , Lipopolissacarídeos/química , Streptococcus mitis/genética , Streptococcus mitis/metabolismo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Ácidos Teicoicos/química
3.
J Biol Chem ; 293(31): 12011-12025, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29884769

RESUMO

Streptococcus suis serotype 2 is an important porcine and human pathogen. Lipoteichoic acid (LTA) from S. suis has been suggested to contribute to its virulence, and absence of d-alanylation from the S. suis LTA is associated with increased susceptibility to cationic antimicrobial peptides. Here, using high-resolution NMR spectroscopy and MS analyses, we characterized the LTA structures from three S. suis serotype 2 strains differing in virulence, sequence type (ST), and geographical origin. Our analyses revealed that these strains possess-in addition to the typical type I LTA present in other streptococci-a second, mixed-type series of LTA molecules of high complexity. We observed a ST-specific difference in the incorporation of glycosyl residues into these mixed-type LTAs. We found that strains P1/7 (ST1, high virulence) and SC84 (ST7, very high virulence) can attach a 1,2-linked α-d-Glcp residue as branching substituent to an α-d-Glcp that is 1,3-linked to glycerol phosphate moieties and that is not present in strain 89-1591 (ST25, intermediate virulence). In contrast, the latter strain could glycosylate its LTA at the glycerol O-2 position, which was not observed in the other two strains. Using LTA preparations from WT strains and from mutants with an inactivated prolipoprotein diacylglyceryl transferase, resulting in deficient lipoprotein acylation, we show that S. suis LTAs alone do not induce Toll-like receptor 2-dependent pro-inflammatory mediator production from dendritic cells. In summary, our study reveals an unexpected complexity of LTAs present in three S. suis serotype 2 strains differing in genetic background and virulence.


Assuntos
Adjuvantes Imunológicos/química , Células Dendríticas/efeitos dos fármacos , Lipopolissacarídeos/química , Streptococcus suis/química , Ácidos Teicoicos/química , Transferases/deficiência , Adjuvantes Imunológicos/isolamento & purificação , Adjuvantes Imunológicos/farmacologia , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Expressão Gênica , Glicosilação , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/isolamento & purificação , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Éteres Fosfolipídicos/química , Cultura Primária de Células , Sorogrupo , Streptococcus suis/classificação , Streptococcus suis/patogenicidade , Relação Estrutura-Atividade , Ácidos Teicoicos/isolamento & purificação , Ácidos Teicoicos/farmacologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Transferases/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Virulência
5.
Sci Rep ; 5: 16718, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26577602

RESUMO

Members of the Mitis group of streptococci possess teichoic acids (TAs) as integral components of their cell wall that are unique among Gram-positive bacteria. Both, lipoteichoic (LTA) and wall teichoic acid, are formed by the same biosynthetic pathway, are of high complexity and contain phosphorylcholine (P-Cho) residues. These residues serve as anchors for choline-binding proteins (CBPs), some of which have been identified as virulence factors of the human pathogen Streptococcus pneumoniae. We investigated the LTA structure of its close relative Streptococcus oralis. Our analysis revealed that S. oralis Uo5 LTA has an overall architecture similar to pneumococcal LTA (pnLTA) and can be considered as a subtype of type IV LTA. Its structural complexity is even higher than that of pnLTA and its composition differs in number and type of carbohydrate moieties, inter-residue connectivities and especially the P-Cho substitution pattern. Here, we report the occurrence of a saccharide moiety substituted with two P-Cho residues, which is unique as yet in bacterial derived surface carbohydrates. Finally, we could link the observed important structural variations between S. oralis and S. pneumoniae LTA to the divergent enzymatic repertoire for their TA biosynthesis.


Assuntos
Lipopolissacarídeos/química , Fosforilcolina/química , Streptococcus oralis/química , Ácidos Teicoicos/química , Vias Biossintéticas , Parede Celular/química , Parede Celular/metabolismo , Hidrazinas/farmacologia , Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/metabolismo , Espectrometria de Massas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Fosforilcolina/metabolismo , Streptococcus oralis/metabolismo , Streptococcus pneumoniae/química , Streptococcus pneumoniae/metabolismo , Ácidos Teicoicos/biossíntese , Ácidos Teicoicos/metabolismo
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