Glycoengineering with neuraminic acid analogs to label lipooligosaccharides and detect native sialyltransferase activity in Gram-negative bacteria DOI

Erianna I. Alvarado-Melendez,

Hanna de Jong,

Jet E. M. Hartman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 6, 2024

Abstract Lipooligosaccharides (LOS) are the most abundant cell surface glycoconjugates on outer membrane of Gram-negative bacteria. They play important roles in host-microbe interactions. Certain pathogenic bacteria cap their LOS with sialic acid, N -acetylneuraminic acid (Neu5Ac), to mimic host glycans that among others protects these from recognition by hosts immune system. This process molecular mimicry is not fully understood and remains under investigated. To explore functional role acid-capped lipooligosaccharides at level, it have tools readily available for detection manipulation both Neu5Ac involved sialyltransferases, preferably live We shown native sialyltransferases some can incorporate extracellular unnatural nucleotides onto LOS. here report expanded use bacterial neuraminic acids analogs a reporter group into variety show this approach offers quick strategy screen expression ability exogenous CMP-Neu5Ac decorate glycoconjugates. For selected we also complements two other glycoengineering techniques, Metabolic Oligosaccharide Engineering (MOE) Selective Exo-Enzymatic Labelling (SEEL), together they provide modify, label, detect visualize sialylation

Language: Английский

Prevotella are major contributors of sialidases in the human vaginal microbiome DOI Creative Commons
Paula Pelayo,

Fatima A. Hussain,

Caroline A. Werlang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(36)

Published: Aug. 26, 2024

Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and vaginosis (BV). These negative effects may arise from sialidase-mediated degradation of protective mucus layer cervicovaginal environment. Prior biochemical studies vaginal sialidases have focused solely on BV-associated organism Gardnerella vaginalis . Despite their implications for sexual reproductive health, other bacteria not been characterized. Here, we show that Prevotella species produce possess variable toward mucin substrates. The sequences genes presence are largely conserved across clades different geographies, hinting at importance globally. Finally, find transcripts, those encoding mucin-degrading timonensis , highly prevalent abundant human genomes transcriptomes. Together, our results identify as a critical source microbiome, improving understanding this detrimental activity.

Language: Английский

Citations

7

Prevotellaare major contributors of sialidases in the human vaginal microbiome DOI Open Access
Paula Pelayo,

Fatima A. Hussain,

Caroline A. Werlang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Abstract Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and vaginosis. These negative effects may arise from sialidase-mediated degradation of protective mucus layer cervicovaginal environment. Prior biochemical studies vaginal sialidases have focused solely on vaginosis-associated organism Gardnerella vaginalis . Despite their implications for sexual reproductive health, other bacteria not been characterized. Here, we show that Prevotella species produce active possess variable toward mucin. are highly conserved across clades different geographies, hinting at importance globally. Finally, find sialidases, mucin-degrading enzymes timonensis , prevalent abundant human metagenomes metatranscriptomes, Together, our results identify as a critical source microbiome, improving understanding this detrimental activity. Significance Statement Sialidase microbiome increased vaginosis adverse outcomes. release sialic acid host-derived glycans environment, altering structures functions. However, limited to one genus, In work, characterize multiple genus We more microbial communities than sialidases. Our work highlights an underappreciated important both therapeutic development.

Language: Английский

Citations

4

Early prediction of preeclampsia using the first trimester vaginal microbiome DOI Creative Commons
William F. Kindschuh, George I. Austin, Yoli Meydan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Preeclampsia is a severe obstetrical syndrome which contributes to 10-15% of all maternal deaths. Although the mechanisms underlying systemic damage in preeclampsia-such as impaired placentation, endothelial dysfunction, and immune dysregulation-are well studied, initial triggers condition remain largely unknown. Furthermore, although pathogenesis preeclampsia begins early pregnancy, there are no diagnostics for this life-threatening syndrome, typically diagnosed much later, after has already manifested. Here, we performed deep metagenomic sequencing multiplex immunoassays vaginal samples collected during first trimester from 124 pregnant individuals, including 62 who developed with features. We identified multiple significant associations between factors, microbes, clinical preeclampsia. These vary BMI, stratification revealed strong

Language: Английский

Citations

1

Glycoengineering with neuraminic acid analogs to label lipooligosaccharides and detect native sialyltransferase activity in Gram-negative bacteria DOI

Erianna I. Alvarado-Melendez,

Hanna de Jong,

Jet E. M. Hartman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 6, 2024

Abstract Lipooligosaccharides (LOS) are the most abundant cell surface glycoconjugates on outer membrane of Gram-negative bacteria. They play important roles in host-microbe interactions. Certain pathogenic bacteria cap their LOS with sialic acid, N -acetylneuraminic acid (Neu5Ac), to mimic host glycans that among others protects these from recognition by hosts immune system. This process molecular mimicry is not fully understood and remains under investigated. To explore functional role acid-capped lipooligosaccharides at level, it have tools readily available for detection manipulation both Neu5Ac involved sialyltransferases, preferably live We shown native sialyltransferases some can incorporate extracellular unnatural nucleotides onto LOS. here report expanded use bacterial neuraminic acids analogs a reporter group into variety show this approach offers quick strategy screen expression ability exogenous CMP-Neu5Ac decorate glycoconjugates. For selected we also complements two other glycoengineering techniques, Metabolic Oligosaccharide Engineering (MOE) Selective Exo-Enzymatic Labelling (SEEL), together they provide modify, label, detect visualize sialylation

Language: Английский

Citations

0