Group B Streptococcus Drives Major Transcriptomic Changes in the Colonic Epithelium

Domínguez, Kristen; Lindon, April K.; Gibbons, Justin; Darch, Sophie E.; Randis, Tara M.

doi:10.1128/iai.00035-23

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…We found that GBS meningitis is associated with more severe clinical manifestations and worse long-term neurological outcomes in neonates. Most of the GBS isolates that caused neonatal meningitis in our cohort belong to the type III/CC17 and type Ib/CC12 strains, which is compatible with previous studies [4,6,[21][22][23][24]. WGS was used to investigate the genetic differences between the GBS isolates of neonatal meningitis and those that caused neonatal sepsis in our cohort, and we found the presence of BspC, HvgA, and PezT genes, as well as ICESag37, to be potentially associated with the occurrence of GBS meningitis.…”

Section: Discussionsupporting

confidence: 89%

“…Compared to numerous studies that have investigated the molecular epidemiology of neonatal GBS invasive diseases and colonization in pregnant women, relatively fewer studies have focused on GBS meningitis [4,21,22]. We found that GBS meningitis is associated with more severe clinical manifestations and worse long-term neurological outcomes in neonates.…”

Section: Discussionmentioning

confidence: 61%

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The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates

Hsu,

Lu,

Chu

et al. 2023

IJMS

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Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 61%

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates

Hsu,

Lu,

Chu

et al. 2023

IJMS

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“…After birth, GBS is capable of colonizing the infant GI tract and can subsequently disrupt the intestinal barrier and spread systemically to the brain, resulting in meningitis and LOD. Previous studies have used murine neonatal models of GBS LOD that use either oral gavage of postnatal day 5 (P5) and P10 pups or intraperitoneal injection of P2 and P5 pups ( 16 , 19 – 21 , 33 ). We sought to modify the P2 neonatal meningitis infection model to incorporate direct GI colonization of P2 pups to mimic LOD at this age ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We also determined that GBS glycolipids are important for bloodstream survival in an established hematogenous murine model of meningitis. To further investigate GBS LOD, we adapted a neonatal meningitis model ( 16 , 19 , 20 , 33 ) by directly seeding the gut of P2 mice with GBS and monitoring systemic spread. In neonatal mice, we observed significant attenuation of GBS∆ iagB with decreased bloodstream survival compared to WT GBS.…”

Section: Discussionmentioning

confidence: 99%

“…The neonatal gut is more susceptible to translocation of bacterial pathogens due to it being a weaker barrier than in adults because it contains a shorter cell height, lower barrier integrity, as well as a lower innate immune response and underdeveloped immune system (17). GBS GI colonization promotes transcriptional changes in the intestinal epithelial barrier resulting in decreased barrier integrity, allowing GBS translocation and systemic spread via the bloodstream (16,(18)(19)(20). Currently, the only factor known to affect GBS GI colonization is the capsule (21), yet other factors that mediate GI colonization, barrier translocation, and systemic spread are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Streptococcus agalactiae glycolipids promote virulence by thwarting immune cell clearance

Joyce,

Kim,

Spencer

et al. 2024

Sci. Adv.

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Streptococcus agalactiae [group B Streptococcus (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen interactions, and the functions of glycolipids are yet to be fully elucidated. GBS synthesizes three major glycolipids: glucosyl-diacylglycerol (Glc-DAG), diglucosyl-DAG (Glc 2 -DAG), and lysyl-Glc-DAG (Lys-Glc-DAG). Here, we identify the enzyme, IagB, as responsible for biosynthesis of Glc-DAG, the precursor for the two other glycolipids in GBS. To examine the collective role of glycolipids to GBS virulence, we adapted a murine model of neonatal meningitis to simulate LOD. The GBS∆ iagB mutant traversed the gut-epithelial barrier comparable to wild type but was severely attenuated in bloodstream survival, resulting in decreased bacterial loads in the brain. The GBS∆ iagB mutant was more susceptible to neutrophil killing and membrane targeting by host antimicrobial peptides. This work reveals an unexplored function of GBS glycolipids with their ability to protect the bacterial cell from host antimicrobial killing.

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Insights into Women's health: Exploring the vaginal microbiome, quorum sensing dynamics, and therapeutic potential of quorum sensing quenchers

Núño,

Jensen,

O'Connor

et al. 2024

Molecular Aspects of Medicine

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Group B Streptococcus Drives Major Transcriptomic Changes in the Colonic Epithelium

Abstract: Group B Streptococcus (GBS) is a leading cause of infant sepsis worldwide. Colonization of the gastrointestinal tract is a critical precursor to late-onset disease in exposed newborns.

Cited by 7 publications

References 27 publications

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates

Streptococcus agalactiae glycolipids promote virulence by thwarting immune cell clearance

Insights into Women's health: Exploring the vaginal microbiome, quorum sensing dynamics, and therapeutic potential of quorum sensing quenchers

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