More Like this

1. Anti‐biofilm Activity of Human Milk Oligosaccharides in Clinical Strains of Streptococcus agalactiae with Diverse Capsular and Sequence Types

   https://doi.org/10.1002/cbic.202200643  

   Moore, Rebecca E. ; Spicer, Sabrina K. ; Talbert, Julie A. ; Manning, Shannon D. ; Townsend, Steven D. ; Gaddy, Jennifer A. ( February 2023 , ChemBioChem)

   Group BStreptococcus(GBS) is an encapsulated Gram‐positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short‐chain sugars that have recently been shown to possess antimicrobial and anti‐biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO‐dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular‐type‐ and sequence‐type‐specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST‐1, ST‐12, ST‐19, and ST‐23 strains. Interestingly, CpsIa as well as ST‐7 and ST‐17 were not susceptible to the anti‐biofilm activity of HMOs, underscoring the strain‐specific effects of these important antimicrobial molecules against the perinatal pathogenStreptococcus agalactiae.

    

   more » « less
2. The Diverse Antimicrobial Activities of Human Milk Oligosaccharides against Group B Streptococcus

   https://doi.org/10.1002/cbic.202100423  

   Moore, Rebecca E. ; Townsend, Steven D. ; Gaddy, Jennifer A. ( October 2021 , ChemBioChem)

   Streptococcus agalactiaeor Group BStreptococcus(GBS) is a Gram‐positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants. However, human milk has also been shown to have protective effects against infection; a characteristic that is likely derived from antimicrobial and immunomodulatory properties of molecules that comprise human milk. Recent evidence suggests that human milk oligosaccharides (HMOs), short‐chain sugars that comprise 8–20 % of breast milk, have antimicrobial and anti‐biofilm activity against GBS and other bacterial pathogens. Additionally, HMOs have been shown to potentiate the activity of antibiotics against GBS. This review presents the most recent published work that studies the interaction between HMOs and GBS.

    

   more » « less
3. Bacterial multispecies interaction mechanisms dictate biogeographic arrangement between the oral commensals Corynebacterium matruchotii and Streptococcus mitis

   https://doi.org/10.1128/msystems.00115-23  

   Almeida, Eric ; Puri, Surendra ; Labossiere, Alex ; Elangovan, Subashini ; Kim, Jiyeon ; Ramsey, Matthew ( October 2023 , mSystems)

   Traxler, Matthew F. (Ed.)

   Polymicrobial biofilms are present in many environments particularly in the human oral cavity where they can prevent or facilitate the onset of disease. While recent advances have provided a clear picture of both the constituents and their biogeographic arrangement, it is still unclear what mechanisms of interaction occur between individual species in close proximity within these communities. In this study, we investigated two mechanisms of interaction between the highly abundant supragingival plaque (SUPP) commensalCorynebacterium matruchotiiandStreptococcus mitiswhich are directly adjacent/attachedin vivo. We discovered thatC. matruchotiienhanced the fitness of streptococci dependent on its ability to detoxify streptococcal-produced hydrogen peroxide and its ability to oxidize lactate also produced by streptococci. We demonstrate that the fitness of adjacent streptococci was linked to that ofC. matruchotiiand that these mechanisms support the previously described “corncob” arrangement between these species but that this is favorable only in aerobic conditions. Furthermore, we utilized scanning electrochemical microscopy to quantify lactate production and consumption between individual bacterial cells for the first time, revealing that lactate oxidation provides a fitness benefit toS. mitisnot due to pH mitigation. This study describes mechanistic interactions between two highly abundant human commensals that can explain their observedin vivospatial arrangements and suggest a way by which they may help preserve a healthy oral bacterial community.

   As the microbiome era matures, the need for mechanistic interaction data between species is crucial to understand how stable microbiomes are preserved, especially in healthy conditions where the microbiota could help resist opportunistic or exogenous pathogens. Here we reveal multiple mechanisms of interaction between two commensals that dictate their biogeographic relationship to each other in previously described structures in human supragingival plaque. Using a novel variation for chemical detection, we observed metabolite exchange between individual bacterial cells in real time validating the ability of these organisms to carry out metabolic crossfeeding at distal and temporal scales observedin vivo. These findings reveal one way by which these interactions are both favorable to the interacting commensals and potentially the host.

    

   more » « less
4. Ear mite infection is associated with altered microbial communities in genetically depauperate Santa Catalina Island foxes ( Urocyon littoralis catalinae )

   https://doi.org/10.1111/mec.15325  

   DeCandia, Alexandra L. ; Brenner, Lara J. ; King, Julie L. ; vonHoldt, Bridgett M. ( January 2020 , Molecular Ecology)

   The host‐associated microbiome is increasingly recognized as a critical player in health and immunity. Recent studies have shown that disruption of commensal microbial communities can contribute to disease pathogenesis and severity. Santa Catalina Island foxes (Urocyon littoralis catalinae) present a compelling system in which to examine microbial dynamics in wildlife due to their depauperate genomic structure and extremely high prevalence of ceruminous gland tumors. Although the precise cause is yet unknown, infection with ear mites (Otodectes cynotis) has been linked to chronic inflammation, which is associated with abnormal cell growth and tumor development. Given the paucity of genomic variation in these foxes, other dimensions of molecular diversity, such as commensal microbes, may be critical to host response and disease pathology. We characterized the host‐associated microbiome across six body sites of Santa Catalina Island foxes, and performed differential abundance testing between healthy and mite‐infected ear canals. We found that mite infection was significantly associated with reduced microbial diversity and evenness, with the opportunistic pathogenStaphylococcus pseudintermediusdominating the ear canal community. These results suggest that secondary bacterial infection may contribute to the sustained inflammation associated with tumor development. As the emergence of antibiotic resistant strains remains a concern of the medical, veterinary, and conservation communities, uncovering high relative abundance ofS. pseudintermediusprovides critical insight into the pathogenesis of this complex system. Through use of culture‐independent sequencing techniques, this study contributes to the broader effort of applying a more inclusive understanding of molecular diversity to questions within wildlife disease ecology.

    

   more » « less
5. A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

   https://doi.org/10.1128/mBio.00076-20  

   Chambers, Schuyler A. ; Moore, Rebecca E. ; Craft, Kelly M. ; Thomas, Harrison C. ; Das, Rishub ; Manning, Shannon D. ; Codreanu, Simona G. ; Sherrod, Stacy D. ; Aronoff, David M. ; McLean, John A. ; et al ( April 2020 , mBio)

   ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics. 

   more » « less