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  1. Article ; Online: Group B Streptococcus and diabetes: Finding the sweet spot.

    Keogh, Rebecca A / Doran, Kelly S

    PLoS pathogens

    2023  Volume 19, Issue 2, Page(s) e1011133

    MeSH term(s) Humans ; Diabetes Mellitus ; Streptococcus agalactiae
    Language English
    Publishing date 2023-02-16
    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.1011133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Detection and Quantification of Secreted Nuclease Activity in Staphylococcus aureus Culture Supernatants.

    Wiemels, Richard E / Keogh, Rebecca A / Carroll, Ronan K

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2341, Page(s) 17–24

    Abstract: Staphylococcal secreted nuclease contributes to S. aureus virulence by degrading neutrophil extracellular traps (NETs), which allows the bacterium to evade the host immune system and has also been shown to promote biofilm dispersal. In this chapter, two ... ...

    Abstract Staphylococcal secreted nuclease contributes to S. aureus virulence by degrading neutrophil extracellular traps (NETs), which allows the bacterium to evade the host immune system and has also been shown to promote biofilm dispersal. In this chapter, two methods for detecting nuclease activity are described, both of which have increased sensitivity compared to the traditional nuclease agar method.
    MeSH term(s) Animals ; Bacterial Proteins/analysis ; Bacterial Proteins/metabolism ; Bacteriological Techniques ; Extracellular Traps/metabolism ; Immune Evasion ; Male ; Micrococcal Nuclease/analysis ; Micrococcal Nuclease/metabolism ; Salmon/genetics ; Spermatozoa/chemistry ; Staphylococcus aureus/enzymology ; Staphylococcus aureus/pathogenicity ; Virulence Factors/analysis ; Virulence Factors/metabolism
    Chemical Substances Bacterial Proteins ; Virulence Factors ; nuc protein, staphylococcus ; Micrococcal Nuclease (EC 3.1.31.1)
    Language English
    Publishing date 2021-07-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1550-8_3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Staphylococcus aureus CamS lipoprotein is a repressor of toxin production that shapes host-pathogen interaction.

    Schilcher, Katrin / Severn, Morgan M / Jenul, Christian / Avina, Young-Saeng C / Keogh, Rebecca A / Horswill, Alexander R

    PLoS biology

    2024  Volume 22, Issue 1, Page(s) e3002451

    Abstract: Lipoproteins of the opportunistic pathogen Staphylococcus aureus play a crucial role in various cellular processes and host interactions. Consisting of a protein and a lipid moiety, they support nutrient acquisition and anchor the protein to the ... ...

    Abstract Lipoproteins of the opportunistic pathogen Staphylococcus aureus play a crucial role in various cellular processes and host interactions. Consisting of a protein and a lipid moiety, they support nutrient acquisition and anchor the protein to the bacterial membrane. Recently, we identified several processed and secreted small linear peptides that derive from the secretion signal sequence of S. aureus lipoproteins. Here, we show, for the first time, that the protein moiety of the S. aureus lipoprotein CamS has a biological role that is distinct from its associated linear peptide staph-cAM373. The small peptide was shown to be involved in interspecies horizontal gene transfer, the primary mechanism for the dissemination of antibiotic resistance among bacteria. We provide evidence that the CamS protein moiety is a potent repressor of cytotoxins, such as α-toxin and leukocidins. The CamS-mediated suppression of toxin transcription was reflected by altered disease severity in in vivo infection models involving skin and soft tissue, as well as bloodstream infections. Collectively, we have uncovered the role of the protein moiety of the staphylococcal lipoprotein CamS as a previously uncharacterized repressor of S. aureus toxin production, which consequently regulates virulence and disease outcomes. Notably, the camS gene is conserved in S. aureus, and we also demonstrated the muted transcriptional response of cytotoxins in 2 different S. aureus lineages. Our findings provide the first evidence of distinct biological functions of the protein moiety and its associated linear peptide for a specific lipoprotein. Therefore, lipoproteins in S. aureus consist of 3 functional components: a lipid moiety, a protein moiety, and a small linear peptide, with putative different biological roles that might not only determine the outcome of host-pathogen interactions but also drive the acquisition of antibiotic resistance determinants.
    MeSH term(s) Humans ; Staphylococcus aureus/genetics ; Lipoproteins/genetics ; Staphylococcal Infections ; Host-Pathogen Interactions ; Cell Adhesion Molecules ; Cytotoxins ; Peptides
    Chemical Substances Lipoproteins ; Cell Adhesion Molecules ; Cytotoxins ; Peptides
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002451
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  4. Article: Androgens at the skin surface regulate

    John, Maria Sindhura / Chinnappan, Mahendran / Artami, Methinee / Bhattacharya, Mohini / Keogh, Rebecca A / Kavanaugh, Jeffrey / Sharma, Tripti / Horswill, Alexander R / Harris-Tryon, Tamia A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Staphylococcus aureus,: One-sentence summary: Testosterone ... ...

    Abstract Staphylococcus aureus,
    One-sentence summary: Testosterone promotes
    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.10.579753
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus.

    Wittekind, Marcus A / Frey, Andrew / Bonsall, Abigail E / Briaud, Paul / Keogh, Rebecca A / Wiemels, Richard E / Shaw, Lindsey N / Carroll, Ronan K

    Molecular microbiology

    2022  Volume 117, Issue 5, Page(s) 1196–1212

    Abstract: Staphylococcus aureus is a Gram-positive commensal that can also cause a variety of infections in humans. S. aureus virulence factor gene expression is under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and two- ... ...

    Abstract Staphylococcus aureus is a Gram-positive commensal that can also cause a variety of infections in humans. S. aureus virulence factor gene expression is under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and two-component systems (TCS). Previous work in our laboratory demonstrated that overexpression of the sRNA tsr37 leads to an increase in bacterial aggregation. Here, we demonstrate that the clumping phenotype is dependent on a previously unannotated 88 amino acid protein encoded within the tsr37 sRNA transcript (which we named ScrA for S. aureus clumping regulator A). To investigate the mechanism of action of ScrA we performed proteomics and transcriptomics in a ScrA overexpressing strain and show that a number of surface adhesins are upregulated, while secreted proteases are downregulated. Results also showed upregulation of the SaeRS TCS, suggesting that ScrA is influencing SaeRS activity. Overexpression of ScrA in a saeR mutant abrogates the clumping phenotype confirming that ScrA functions via the Sae system. Finally, we identified the ArlRS TCS as a positive regulator of scrA expression. Collectively, our results show that ScrA is an activator of the SaeRS system and suggests that ScrA may act as an intermediary between the ArlRS and SaeRS systems.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression ; Gene Expression Regulation, Bacterial/genetics ; Humans ; Protein Kinases/metabolism ; RNA, Small Untranslated/metabolism ; Staphylococcal Infections ; Staphylococcus aureus/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Virulence/genetics
    Chemical Substances Bacterial Proteins ; RNA, Small Untranslated ; Transcription Factors ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2022-04-15
    Publishing country England
    Document type Journal Article ; 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.14901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Rapid electrochemical detection of

    Ramanujam, Ashwin / Neyhouse, Bertrand / Keogh, Rebecca A / Muthuvel, Madhivanan / Carroll, Ronan K / Botte, Gerardine G

    Chemical engineering journal (Lausanne, Switzerland : 1996)

    2020  Volume 411, Page(s) 128453

    Abstract: A standalone electrochemical method for detecting the ... ...

    Abstract A standalone electrochemical method for detecting the bacterium
    Language English
    Publishing date 2020-01-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2012137-4
    ISSN 1873-3212 ; 1385-8947
    ISSN (online) 1873-3212
    ISSN 1385-8947
    DOI 10.1016/j.cej.2021.128453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection.

    Akbari, Madeline S / Keogh, Rebecca A / Radin, Jana N / Sanchez-Rosario, Yamil / Johnson, Michael D L / Horswill, Alexander R / Kehl-Fie, Thomas E / Burcham, Lindsey R / Doran, Kelly S

    mBio

    2023  Volume 14, Issue 4, Page(s) e0030423

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

    Abstract Group B
    MeSH term(s) Mice ; Animals ; Diabetes Mellitus, Experimental ; Neutrophils ; Wound Infection ; Streptococcal Infections/microbiology ; Streptococcus agalactiae/genetics
    Language English
    Publishing date 2023-06-26
    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.00304-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Staphylococcus aureus Responds to Physiologically Relevant Temperature Changes by Altering Its Global Transcript and Protein Profile.

    Bastock, Raeven A / Marino, Emily C / Wiemels, Richard E / Holzschu, Donald L / Keogh, Rebecca A / Zapf, Rachel L / Murphy, Erin R / Carroll, Ronan K

    mSphere

    2021  Volume 6, Issue 2

    Abstract: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    MeSH term(s) Bacterial Proteins/analysis ; Cells, Cultured ; Epithelial Cells/microbiology ; Gene Expression Regulation, Bacterial ; Humans ; Nose/cytology ; Proteome ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/chemistry ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism ; Temperature ; Transcriptome ; Virulence Factors/genetics
    Chemical Substances Bacterial Proteins ; Proteome ; Virulence Factors
    Language English
    Publishing date 2021-03-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/mSphere.01303-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Genomic Analyses Identify Manganese Homeostasis as a Driver of Group B Streptococcal Vaginal Colonization.

    Burcham, Lindsey R / Akbari, Madeline S / Alhajjar, Norhan / Keogh, Rebecca A / Radin, Jana N / Kehl-Fie, Thomas E / Belew, Ashton T / El-Sayed, Najib M / McIver, Kevin S / Doran, Kelly S

    mBio

    2022  Volume 13, Issue 3, Page(s) e0098522

    Abstract: Group B Streptococcus (GBS) is associated with severe ... ...

    Abstract Group B Streptococcus (GBS) is associated with severe infections
    MeSH term(s) Animals ; Female ; Genomics ; Homeostasis ; Hydrogen Peroxide ; Leukocyte L1 Antigen Complex ; Manganese ; Mice ; Paraquat ; Pregnancy ; Streptococcal Infections/genetics ; Streptococcus agalactiae/genetics ; Vagina
    Chemical Substances Leukocyte L1 Antigen Complex ; Manganese (42Z2K6ZL8P) ; Hydrogen Peroxide (BBX060AN9V) ; Paraquat (PLG39H7695)
    Language English
    Publishing date 2022-06-06
    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.00985-22
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