Biology subjects

Manning, S. D.

Publications and source records attributed to Manning, S. D..

3 recordsLinked to original sources

bioRxiv2023

Recovery of the gut microbiome following enteric infection and persistence of antimicrobial resistance genes in specific microbial hosts

Enteric pathogens cause widespread foodborne illness and are increasingly found to harbor antimicrobial resistance. The ecological impact of these pathogens on the human gut microbiome and resistome, however, has yet to be fully elucidated. This study applied shotgun metagenome sequencing to stools from 60 patients (cases) with enteric bacterial infections for comparison to stools collected from the same patients post-recovery (follow-ups). Overall, the case samples harbored more antimicrobial resistance genes (ARGs) and had greater resistome diversity than the follow-up samples (p<0.001), while follow-ups had much more diverse microbiomes (p<0.001). Although cases were primarily defined by genera Escherichia, Salmonella, and Shigella along with ARGs for multi-compound and multidrug resistance, follow-ups had a greater abundance of Bacteroidetes and Firmicutes phyla and genes for tetracycline, macrolides, lincosamides, and streptogramins (MLS), and aminoglycoside resistance. A host-tracking analysis revealed that Escherichia was the primary carrier of ARGs in both cases and follow-ups, with a greater abundance occurring during infection. Eleven distinct extended spectrum beta-lactamases (ESBLs) were identified during infection, some of which appear to be lost or transferred to different microbial hosts upon recovery. The increasing incidence of disease caused by foodborne pathogens, coupled with their evolving role in harboring and transferring antimicrobial resistance determinants within communities, justifies further examination of the repercussions of enteric infection on human gut ecology.

microbiology↗

bioRxiv2022

Group B streptococcal membrane vesicles induce proinflammatory cytokine production and are sensed in an NLRP3 inflammasome-dependent mechanism in human macrophages

Group B Streptococcus (GBS) is a major cause of fetal and neonatal mortality worldwide. Many of the adverse effects associated with invasive GBS are associated with inflammation that leads to chorioamnionitis, preterm birth, sepsis, and meningitis; therefore, understanding bacterial factors that promote inflammation is of critical importance. Membrane vesicles (MVs), which are produced by many pathogenic and non-pathogenic bacteria, may modulate host inflammatory responses. In mice, GBS MVs injected intra-amniotically can induce preterm birth and fetal death. Although it is known that GBS MVs induce large-scale leukocyte recruitment into infected tissues, the immune effectors driving these responses are unclear. Here, we hypothesized that macrophages respond to GBS-derived MVs by producing proinflammatory cytokines and are recognized through one or more pattern recognition receptors. We show that THP-1 macrophage-like cells produce high levels of neutrophil- and monocyte-specific chemokines in response to MVs derived from different clinical isolates of GBS. Interleukin (IL)-1{beta} was significantly upregulated in response to MVs, which was independent of NF-kB signaling but dependent on both caspase-1 and NLRP3. These data indicate that MVs contain one or more pathogen-associated molecular patterns that can be sensed by the immune system. Furthermore, this study identifies the NLRP3 inflammasome as a novel sensor of GBS MVs. Our data additionally indicate that MVs may serve as immune effectors that can be targeted for immunotherapeutics, particularly given that similar responses were observed across this subset of GBS isolates.

immunology↗

bioRxiv2021

Production and composition of group B streptococcal membrane vesicles varies across diverse lineages

Although the neonatal and fetal pathogen Group B Streptococcus (GBS) asymptomatically colonizes the vaginal tract of [~]30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes. Because the relationship between strain variation and vesicle composition or production is unknown, we sought to quantify MV production and examine the protein composition, using label-free proteomics on MVs produced by diverse clinical GBS strains representing three phylogenetically distinct lineages. We found that MV production varied across strains, with certain strains displaying nearly two-fold increases in production relative to others. Hierarchical clustering and principal component analysis of the proteomes revealed that MV composition is lineage-dependent but independent of clinical phenotype. Multiple proteins that contribute to virulence or immunomodulation, including hyaluronidase, C5a peptidase, and sialidases, were differentially abundant in MVs, and were partially responsible for this divergence. Together, these data indicate that production and composition of GBS MVs vary in a strain-dependent manner, suggesting that MVs have lineage-specific functions relating to virulence. Such differences may contribute to variation in clinical phenotypes observed among individuals infected with GBS strains representing distinct lineages.

microbiology↗