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  1. Article ; Online: Evolving understanding of the type VII secretion system in Gram-positive bacteria.

    Spencer, Brady L / Doran, Kelly S

    PLoS pathogens

    2022  Volume 18, Issue 7, Page(s) e1010680

    MeSH term(s) Bacterial Proteins ; Gram-Positive Bacteria ; Type VII Secretion Systems
    Chemical Substances Bacterial Proteins ; Type VII Secretion Systems
    Language English
    Publishing date 2022-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Virtual Streptococcal Seminar Series and Trainee Symposium: Adaptations of a Research Community during the COVID-19 Pandemic.

    Spencer, Brady L / Doran, Kelly S / Burcham, Lindsey R

    Journal of microbiology & biology education

    2021  Volume 22, Issue 1

    Abstract: The COVID-19 pandemic has forced academic research communities to develop online means of learning, networking, and engaging in new research. To allow increased interaction and engagement of the streptococcal research community during the COVID-19 ... ...

    Abstract The COVID-19 pandemic has forced academic research communities to develop online means of learning, networking, and engaging in new research. To allow increased interaction and engagement of the streptococcal research community during the COVID-19 shutdown, we organized the Virtual Streptococcal Seminar Series and Virtual Streptococcal Trainee Symposium and advertised via e-mail and social media outlets. The seminar series initially met weekly on Thursdays at 12 pm Eastern Daylight Time and transitioned to monthly seminars, while the trainee symposium spanned 3 days in September 2020. In this study, we analyzed seminar attendance data and online recording accesses from the first 20 seminars and found community engagement to be independent of speaker gender, career stage, geographic location, and organism of interest, with an average of 124 live attendees and 1,683 recording accesses per seminar. We also report attendance and speaker statistics from the 3-day Virtual Streptococcal Trainee Symposium, which hosted a total of 38 trainees from five continents presenting on
    Language English
    Publishing date 2021-03-31
    Publishing country United States
    Document type Journal Article
    ISSN 1935-7877
    ISSN 1935-7877
    DOI 10.1128/jmbe.v22i1.2479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence.

    Spencer, Brady L / Tak, Uday / Mendonça, Jéssica C / Nagao, Prescilla E / Niederweis, Michael / Doran, Kelly S

    PLoS pathogens

    2021  Volume 17, Issue 12, Page(s) e1010121

    Abstract: Type VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, and/or interbacterial killing in a few genera. Bioinformatic analysis ... ...

    Abstract Type VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, and/or interbacterial killing in a few genera. Bioinformatic analysis indicates that isolates of Group B Streptococcus (GBS) encode at least four distinct subtypes of T7SS machinery, three of which encode adjacent putative T7SS effectors with WXG and LXG motifs. However, the function of T7SS in GBS pathogenesis is unknown. Here we assessed the role of the most abundant GBS T7SS subtype during GBS pathogenesis. In a murine model of hematogenous meningitis, mice infected with GBS lacking a functional T7SS or lacking the secreted WXG100 effector EsxA exhibited less mortality, lower bacterial burdens in tissues, and decreased inflammation in the brain compared to mice infected with the parental GBS strain. We further showed that this T7SS induces cytotoxicity in brain endothelium and that EsxA contributes to these cytotoxicity phenotypes in a WXG motif-dependent manner. Finally, we determined that EsxA is a pore-forming protein, thus demonstrating the first role for a non-mycobacterial EsxA homolog in pore formation. This work reveals the importance of a T7SS in host-GBS interactions and has implications for T7SS effector function in other Gram-positive bacteria.
    MeSH term(s) Animals ; Bacterial Proteins/metabolism ; Cells, Cultured ; Humans ; Mice ; Streptococcal Infections/metabolism ; Streptococcus agalactiae/metabolism ; Streptococcus agalactiae/pathogenicity ; Type VII Secretion Systems/metabolism ; Virulence/physiology
    Chemical Substances Bacterial Proteins ; Type VII Secretion Systems
    Language English
    Publishing date 2021-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Complete Genome Sequence of Neonatal Clinical Group B Streptococcal Isolate CJB111.

    Spencer, Brady L / Chatterjee, Anushila / Duerkop, Breck A / Baker, Carol J / Doran, Kelly S

    Microbiology resource announcements

    2021  Volume 10, Issue 2

    Abstract: ... Group ... ...

    Abstract Group B
    Language English
    Publishing date 2021-01-14
    Publishing country United States
    Document type Journal Article
    ISSN 2576-098X
    ISSN (online) 2576-098X
    DOI 10.1128/MRA.01268-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Formation and function of the meningeal arachnoid barrier around the developing mouse brain.

    Derk, Julia / Como, Christina N / Jones, Hannah E / Joyce, Luke R / Kim, Sol / Spencer, Brady L / Bonney, Stephanie / O'Rourke, Rebecca / Pawlikowski, Brad / Doran, Kelly S / Siegenthaler, Julie A

    Developmental cell

    2023  Volume 58, Issue 8, Page(s) 635–644.e4

    Abstract: The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and ... ...

    Abstract The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and timing are largely unknown. Here, we show that mouse arachnoid barrier cell specification requires the repression of Wnt-β-catenin signaling and that constitutively active β-catenin can prevent its formation. We also show that the arachnoid barrier is functional prenatally and, in its absence, a small molecular weight tracer and the bacterium group B Streptococcus can cross into the CNS following peripheral injection. Acquisition of barrier properties prenatally coincides with the junctional localization of Claudin 11, and increased E-cadherin and maturation continues after birth, where postnatal expansion is marked by proliferation and re-organization of junctional domains. This work identifies fundamental mechanisms that drive arachnoid barrier formation, highlights arachnoid barrier fetal functions, and provides novel tools for future studies on CNS barrier development.
    MeSH term(s) Mice ; Animals ; beta Catenin ; Meninges ; Arachnoid ; Blood-Brain Barrier ; Central Nervous System ; Tight Junctions
    Chemical Substances beta Catenin
    Language English
    Publishing date 2023-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2023.03.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Ficolin-2 binds to serotype 35B pneumococcus as it does to serotypes 11A and 31, and these serotypes cause more infections in older adults than in children.

    Geno, K Aaron / Spencer, Brady L / Bae, Sejong / Nahm, Moon H

    PloS one

    2018  Volume 13, Issue 12, Page(s) e0209657

    Abstract: Among 98 serotypes of Streptococcus pneumoniae, only a small subset regularly causes invasive pneumococcal diseases (IPD). We previously demonstrated that serotype 11A binds to ficolin-2 and has low invasiveness in children. Epidemiologic data suggested, ...

    Abstract Among 98 serotypes of Streptococcus pneumoniae, only a small subset regularly causes invasive pneumococcal diseases (IPD). We previously demonstrated that serotype 11A binds to ficolin-2 and has low invasiveness in children. Epidemiologic data suggested, however, that serotype 11A IPD afflicts older adults, possibly indicating reduced ficolin-2-mediated immune protection. Therefore, we studied the epidemiology of ficolin-2-bound serotypes. We obtained IPD case data from the United States Centers for Disease Control and Prevention. We studied three prominent ficolin-2-bound serotypes and their acetyltransferase-deficient variants for ficolin-2 binding and ficolin-2-mediated complement deposition with flow-cytometry. We determined the age distributions of these serotypes from the obtained epidemiologic data. We discovered that the serotype 35B capsule is a novel ficolin-2 ligand due to O-acetylation via WciG. Ficolin-2-mediated complement deposition was observed on serotypes 11A and 35B but not serotype 31 or any O-acetyl transferase deficient derivatives of these serotypes. Serotypes 11A, 35B, and 31 cause more IPD among older adults than children. Studies of the three serotypes provide additional evidence for ficolin-2 providing innate immunity against IPD. The skewed age distribution of the three serotypes suggests that older adults have reduced ficolin-2-mediated immunity and are more susceptible to these serotypes.
    MeSH term(s) Acetylation ; Acetyltransferases/deficiency ; Acetyltransferases/genetics ; Acetyltransferases/immunology ; Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Lectins/genetics ; Lectins/immunology ; Male ; Middle Aged ; Pneumococcal Infections/genetics ; Pneumococcal Infections/immunology ; Pneumococcal Infections/microbiology ; Pneumococcal Infections/pathology ; Protein Binding/genetics ; Serogroup ; Serotyping ; Streptococcus pneumoniae/genetics ; Streptococcus pneumoniae/immunology ; Streptococcus pneumoniae/pathogenicity ; United States ; Young Adult ; Ficolins
    Chemical Substances Lectins ; Acetyltransferases (EC 2.3.1.-)
    Language English
    Publishing date 2018-12-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0209657
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  7. Article ; Online: Global Annotation, Expression Analysis, and Stability of Candidate sRNAs in Group B Streptococcus.

    Keogh, Rebecca A / Spencer, Brady L / Sorensen, Hailee M / Zapf, Rachel L / Briaud, Paul / Bonsall, Abigail E / Doran, Kelly S / Carroll, Ronan K

    mBio

    2021  Volume 12, Issue 6, Page(s) e0280321

    Abstract: Small, noncoding RNAs (sRNAs) are being increasingly identified as important regulatory molecules in prokaryotes. Due to the prevalence of next-generation sequencing-based techniques, such as RNA sequencing (RNA-seq), there is potential for increased ... ...

    Abstract Small, noncoding RNAs (sRNAs) are being increasingly identified as important regulatory molecules in prokaryotes. Due to the prevalence of next-generation sequencing-based techniques, such as RNA sequencing (RNA-seq), there is potential for increased discovery of sRNAs within bacterial genomes; however, these elements are rarely included in annotation files. Consequently, expression values for sRNAs are omitted from most transcriptomic analyses, and mechanistic studies have lagged behind those of protein regulators in numerous bacteria. Two previous studies have identified sRNAs in the human pathogen group B Streptococcus (GBS). Here, we utilize the data from these studies to create updated genome annotation files for the model GBS strains NEM316 and COH1. Using the updated COH1 annotation file, we reanalyze publicly available GBS RNA-seq whole-transcriptome data from GenBank to monitor GBS sRNA expression under a variety of conditions and genetic backgrounds. This analysis generated expression values for 232 putative sRNAs that were overlooked in previous transcriptomic analyses in 21 unique comparisons. To demonstrate the utility of these data, we identify an sRNA that is upregulated during vaginal colonization and demonstrate that overexpression of this sRNA leads to increased bacterial invasion into host epithelial cells. Finally, to monitor RNA degradation, we perform a transcript stability assay to identify highly stable sRNAs and compare stability profiles of sRNA- and protein-coding genes. Collectively, these data provide a wealth of transcriptomic data for putative sRNAs in GBS and a platform for future mechanistic studies.
    MeSH term(s) Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genome, Bacterial ; Humans ; RNA Stability ; RNA, Bacterial/chemistry ; RNA, Bacterial/genetics ; RNA, Bacterial/metabolism ; RNA, Small Untranslated/chemistry ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; Streptococcal Infections/microbiology ; Streptococcus agalactiae/chemistry ; Streptococcus agalactiae/genetics ; Streptococcus agalactiae/metabolism
    Chemical Substances RNA, Bacterial ; RNA, Small Untranslated
    Language English
    Publishing date 2021-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.02803-21
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  8. Article: Enhanced Vulnerability of Diabetic Mice to Hypervirulent

    da Conceição Mendonça, Jéssica / Sobral Pena, João Matheus / Dos Santos Macêdo, Noemi / de Souza Rodrigues, Dayane / de Oliveira, Dayane Alvarinho / Spencer, Brady L / Lopes-Torres, Eduardo José / Burcham, Lindsey R / Doran, Kelly S / Nagao, Prescilla Emy

    Pathogens (Basel, Switzerland)

    2023  Volume 12, Issue 4

    Abstract: Streptococcus ... ...

    Abstract Streptococcus agalactiae
    Language English
    Publishing date 2023-04-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12040580
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  9. Article ; Online: Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract.

    Spencer, Brady L / Job, Alyx M / Robertson, Clare M / Hameed, Zainab A / Serchejian, Camille / Wiafe-Kwakye, Caitlin S / Mendonça, Jéssica C / Apolonio, Morgan A / Nagao, Prescilla E / Neely, Melody N / Korotkova, Natalia / Korotkov, Konstantin V / Patras, Kathryn A / Doran, Kelly S

    Molecular microbiology

    2023  Volume 120, Issue 2, Page(s) 258–275

    Abstract: Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B ... ...

    Abstract Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-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 intraspecies 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 interspecies 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. Furthermore, we observe subtype-specific effects of GBS T7SS on host colonization, as CJB111 subtype I but not CNCTC 10/84 subtype III T7SS promotes GBS vaginal colonization. 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.
    MeSH term(s) Infant, Newborn ; Female ; Humans ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Type VII Secretion Systems/genetics ; Virulence ; Operon/genetics ; Genitalia, Female/metabolism ; Streptococcal Infections/microbiology ; Streptococcus agalactiae/genetics ; Streptococcus agalactiae/metabolism ; Vagina/metabolism ; Vagina/microbiology
    Chemical Substances Bacterial Proteins ; Type VII Secretion Systems
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15115
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  10. Article: Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract.

    Spencer, Brady L / Job, Alyx M / Robertson, Clare M / Hameed, Zainab A / Serchejian, Camille / Wiafe-Kwakye, Caitlin S / Mendonça, Jéssica C / Apolonio, Morgan A / Nagao, Prescilla E / Neely, Melody N / Korotkova, Natalia / Korotkov, Konstantin V / Patras, Kathryn A / Doran, Kelly S

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group ... ...

    Abstract Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.25.525443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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