Biology subjects

Neely, M. N.

Publications and source records attributed to Neely, M. N..

4 recordsLinked to original sources

bioRxiv2025

Interactions between Streptococcus agalactiae and Candida albicans affect persistence and virulence

Streptococcus agalactiae (Group B Streptococcus or GBS), a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, are commensal microbes in most of the population they colonize. However, for certain patients they can cause severe and sometimes fatal infections. Previous research has indicated that GBS and C. albicans can synergize to enhance the colonization of GBS in the bladders of mice, but not much was known prior to this study about how interactions between GBS and C. albicans alter treatment effectiveness and infection outcome in vivo. Results showed that interactions between the two opportunistic pathogens were influenced by media nutrient availability, and that the presence of C. albicans in a culture reduces the effectiveness of certain antibiotics against GBS in vitro. This study also utilized a larval zebrafish model to investigate differences in virulence in solo infections vs co-infections with both pathogens in vivo. Co-infections of GBS and C. albicans into the otic vesicle were found to have increased virulence compared to solo infections of either pathogen. Co-infection also led to an increased GBS burden compared to solo GBS infections. Co-infections of GBS and C. albicans by yolk sac injection were not more virulent than solo infections with either pathogen. However, the antibiotic clindamycin was less effective in preventing mortality in co-infections compared to solo GBS infections. Overall, these findings highlight how interactions between GBS and C. albicans can influence treatment effectiveness and virulence during infection.

microbiology↗

bioRxiv2025

Akkermansia muciniphila Impacts Group B Streptococcus Vaginal Colonization

Streptococcus agalactiae or Group B Streptococcus (GBS) is an opportunistic pathogen that asymptomatically colonizes the vaginal tract of up to 30% of healthy individuals. However, during pregnancy it is associated with adverse pregnancy outcomes, and GBS can be transmitted to the fetus in utero, or the newborn during vaginal birth, resulting in invasive neonatal disease. Previously we identified that Akkermansia muciniphila alters the dynamics of GBS vaginal colonization. However, the global effect of A. muciniphila in the female genital tract remains largely unknown, as it has predominantly been studied in the context of gastrointestinal health. Here we determine that A. muciniphila promotes GBS aggregation and attachment to human vaginal epithelial cells (hVECs). RNA-sequencing analysis revealed that A. muciniphila changed expression of 258 unique GBS genes during hVEC colonization, with many involved in cell wall/membrane/envelope biogenesis. We demonstrate that A. muciniphila-mediated increases in GBS aggregation and attachment to hVECs are dependent on GBS capsule and pili, respectively. Lastly, we found that A. muciniphila promoted GBS aggregation in the murine vaginal lumen and continual treatment with A. muciniphila reduced GBS vaginal persistence. Our results highlight the dynamic impact of A. muciniphila on GBS gene expression and vaginal colonization, as well as demonstrate the probiotic potential of A. muciniphila in the vaginal environment. IMPORTANCEGroup B Streptococcus (GBS) is a frequent colonizer of the vaginal tract of healthy people, however during pregnancy, maternal colonization is associated with adverse pregnancy outcomes. GBS is a leading cause of neonatal sepsis and meningitis and can be transmitted to a newborn during vaginal delivery or by ascension into the uterus during pregnancy. Influence of the vaginal microbiota on GBS pathogenesis remains greatly underappreciated. We have found that GBS is associated with the mucin-degrading intestinal commensal Akkermansia muciniphila, a newly identified colonizer of the vaginal tract. Significance of our research is in identifying the mechanistic impact of this commensal organism on GBS aggregation, cell adherence, and gene expression, as well as its therapeutic potential during GBS vaginal colonization. Unraveling relationships between GBS and the vaginal microbiota will improve maternal and fetal health and may enterprise the development of alternative methods to reduce GBS in utero complications and neonatal disease.

microbiology↗

bioRxiv2025

A fungal pathobiont promotes Streptococcus agalactiae vaginal persistence and pathogenesis through physical and metabolic interactions

Complex polymicrobial interactions at the host interface can shape the mucosal landscape and tip the scales between commensalism and pathogenicity. Here, we use a newly adapted murine model of vaginal colonization to show that the human pathobiont Candida albicans (Ca) supports Group B Streptococcus (GBS) fitness in the vaginal tract and ascension to the uterus. GBS frequently colonizes the vagina asymptomatically; however, during pregnancy, colonization can lead to adverse outcomes and neonatal invasive infection. Using human vaginal isolates of Ca and GBS, we demonstrate that physical interactions contribute to persistence. Triple RNA sequencing of Ca, GBS, and a physiologically relevant model of the human vaginal epithelium reveals that GBS induces arginine biosynthesis in Ca. This drives the expression of bacterial virulence factors and primes GBS for adhesion to the epithelium. We show that interkingdom nutrient exchange can increase GBS pathogenic potential and identify a new target for preventative therapies.

microbiology↗

bioRxiv2023

Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small [a]-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intra-species diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low inter-species and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Further, we observe subtype-specific effects of GBS T7SS on host colonization, as subtype I but not subtype III T7SS promotes GBS vaginal persistence. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.

microbiology↗