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  1. Article ; Online: Out of destruction comes new growth: Pore-forming antimicrobials make pancreas grow.

    Yunker, Rebecca / Bonakdar, Maryam / Vaishnava, Shipra

    Cell metabolism

    2022  Volume 34, Issue 11, Page(s) 1611–1613

    Abstract: Gut-residing bacteria are known to regulate the physiologies of distal organs. However, the mechanism behind the long-distance communication between gut microbes and distal organs remains unknown. In this issue of Cell Metabolism, two studies show that β ...

    Abstract Gut-residing bacteria are known to regulate the physiologies of distal organs. However, the mechanism behind the long-distance communication between gut microbes and distal organs remains unknown. In this issue of Cell Metabolism, two studies show that β cell expansion in the pancreas depends on bacterially induced antimicrobials produced in the gut.
    MeSH term(s) Bacteria/metabolism ; Anti-Infective Agents/pharmacology ; Anti-Infective Agents/metabolism ; Pancreas
    Chemical Substances Anti-Infective Agents
    Language English
    Publishing date 2022-10-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2022.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6169: Show issues Location:
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  2. Article ; Online: Gut commensals expand vitamin A metabolic capacity of the mammalian host.

    Bonakdar, Maryam / Czuba, Lindsay C / Han, Geongoo / Zhong, Guo / Luong, Hien / Isoherranen, Nina / Vaishnava, Shipra

    Cell host & microbe

    2022  Volume 30, Issue 8, Page(s) 1084–1092.e5

    Abstract: Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high ... ...

    Abstract Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.
    MeSH term(s) Animals ; Mammals ; Mice ; Retinoids/metabolism ; Tretinoin/metabolism ; Vitamin A/metabolism
    Chemical Substances Retinoids ; Vitamin A (11103-57-4) ; Tretinoin (5688UTC01R)
    Language English
    Publishing date 2022-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2022.06.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6578: Show issues Location:
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  3. Article ; Online: A Counterselectable Sucrose Sensitivity Marker Permits Efficient and Flexible Mutagenesis in

    Hooven, Thomas A / Bonakdar, Maryam / Chamby, Anna B / Ratner, Adam J

    Applied and environmental microbiology

    2019  Volume 85, Issue 7

    Abstract: Streptococcus ... ...

    Abstract Streptococcus agalactiae
    MeSH term(s) Alleles ; Aminoacyltransferases/genetics ; Bacterial Proteins/genetics ; Cysteine Endopeptidases/genetics ; Gene Editing ; Gene Expression Regulation, Bacterial ; Gene Knockout Techniques ; Genes, Bacterial/genetics ; Genetic Vectors ; Hexosyltransferases/genetics ; Mutagenesis ; Mutation ; Plasmids ; Polymorphism, Genetic ; Streptococcus agalactiae/cytology ; Streptococcus agalactiae/genetics ; Streptococcus agalactiae/metabolism ; Sucrose/metabolism
    Chemical Substances Bacterial Proteins ; Sucrose (57-50-1) ; Aminoacyltransferases (EC 2.3.2.-) ; sortase A (EC 2.3.2.-) ; Hexosyltransferases (EC 2.4.1.-) ; levansucrase (EC 2.4.1.10) ; Cysteine Endopeptidases (EC 3.4.22.-)
    Language English
    Publishing date 2019-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 223011-2
    ISSN 1098-5336 ; 0099-2240
    ISSN (online) 1098-5336
    ISSN 0099-2240
    DOI 10.1128/AEM.03009-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Impact of Circulating Antibody on Group B

    Vaz, Michelle J / Purrier, Sheryl A / Bonakdar, Maryam / Chamby, Anna B / Ratner, Adam J / Randis, Tara M

    Infection and immunity

    2020  Volume 89, Issue 1

    Abstract: Gastrointestinal (GI) colonization with group ... ...

    Abstract Gastrointestinal (GI) colonization with group B
    MeSH term(s) Age Factors ; Animals ; Antibodies, Bacterial/blood ; Antibodies, Bacterial/immunology ; Disease Models, Animal ; Disease Susceptibility ; Gastroenteritis/immunology ; Gastroenteritis/microbiology ; Gastroenteritis/mortality ; Gastroenteritis/pathology ; Host-Pathogen Interactions/immunology ; Immunization ; Mice ; Streptococcal Infections/immunology ; Streptococcal Infections/microbiology ; Streptococcal Infections/mortality ; Streptococcal Infections/pathology ; Streptococcal Vaccines/immunology ; Streptococcus agalactiae/immunology
    Chemical Substances Antibodies, Bacterial ; Streptococcal Vaccines
    Language English
    Publishing date 2020-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00348-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 684: Show issues Location:
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  5. Article ; Online: Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization.

    Baker, Jacqueline A / Lewis, Emma L / Byland, Leah M / Bonakdar, Maryam / Randis, Tara M / Ratner, Adam J

    Vaccine

    2017  Volume 35, Issue 9, Page(s) 1273–1280

    Abstract: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants, and colonization of the maternal genital tract is the primary risk factor for newborn infection. Despite the importance of mucosal colonization in GBS pathogenesis, ... ...

    Abstract Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants, and colonization of the maternal genital tract is the primary risk factor for newborn infection. Despite the importance of mucosal colonization in GBS pathogenesis, relevant host and bacterial factors are incompletely understood. We investigated the role of humoral immunity in clearance of vaginal colonization in vivo. B-cell-deficient mice or those lacking neonatal Fc-receptor, a mediator of IgG transport to the vaginal mucosa, exhibit prolonged GBS vaginal colonization compared to wild type animals. Intranasal but not intramuscular immunization induced systemic and mucosal immune responses and decreased GBS colonization duration without altering initial colonization density. Vaccine-induced clearance of GBS was serotype-specific, suggesting a role for anti-capsule antibodies in protection. Our results support a role for humoral immunity in GBS eradication from the female genital tract and suggest that mucosal vaccination may prime colonization clearance.
    Language English
    Publishing date 2017-03-01
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2017.01.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 458: Show issues

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  6. Article ; Online: The Streptococcus agalactiae Stringent Response Enhances Virulence and Persistence in Human Blood.

    Hooven, Thomas A / Catomeris, Andrew J / Bonakdar, Maryam / Tallon, Luke J / Santana-Cruz, Ivette / Ott, Sandra / Daugherty, Sean C / Tettelin, Hervé / Ratner, Adam J

    Infection and immunity

    2017  Volume 86, Issue 1

    Abstract: Streptococcus ... ...

    Abstract Streptococcus agalactiae
    MeSH term(s) Arginine/genetics ; Bacterial Proteins/genetics ; Cell Communication/genetics ; Gene Expression Regulation, Bacterial/genetics ; Genes, Bacterial/genetics ; Genetic Fitness/genetics ; Hemolysin Proteins/genetics ; Humans ; Hydrolases/genetics ; Operon/genetics ; Perforin/genetics ; Streptococcal Infections/microbiology ; Streptococcus agalactiae/genetics ; Streptococcus agalactiae/pathogenicity ; Transcriptome/genetics ; Virulence/genetics
    Chemical Substances Bacterial Proteins ; Hemolysin Proteins ; Perforin (126465-35-8) ; Arginine (94ZLA3W45F) ; Hydrolases (EC 3.-) ; arginine deiminase (EC 3.5.3.6)
    Language English
    Publishing date 2017-12-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00612-17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 684: Show issues Location:
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  7. Article ; Online: Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast cancer.

    Kwa, Maryann / Li, Xiaochun / Novik, Yelena / Oratz, Ruth / Jhaveri, Komal / Wu, Jennifer / Gu, Ping / Meyers, Marleen / Muggia, Franco / Speyer, James / Iwano, Alyssa / Bonakdar, Maryam / Kozhaya, Lina / Tavukcuoglu, Ece / Budan, Bahar / Raad, Roy / Goldberg, Judith D / Unutmaz, Derya / Adams, Sylvia

    Breast cancer research and treatment

    2017  Volume 168, Issue 1, Page(s) 57–67

    Abstract: Background and purpose: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and ... ...

    Abstract Background and purpose: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in patients with advanced HR-positive breast cancer and assessed changes in circulating immune cell subsets.
    Methods: This was a single-arm phase II trial of exemestane with cyclophosphamide in patients with metastatic HR-positive/HER2-negative breast cancer who had progressed on prior endocrine therapy (ClinicalTrials.gov: NCT01963481). Primary endpoint was progression-free survival (PFS) at 3 months (RECIST 1.1). Secondary objectives included median PFS, objective response rate, duration of response, and safety. Circulating Tregs (FOXP3
    Results: Twenty-three patients were enrolled. Treatment was well tolerated, without grade 4/5 toxicities. Objective responses were seen in 6/23 patients (26.1%; 95% CI 10.2-48.4%) and were durable (median 11.6 months). Three-month PFS rate was 50.1% (95% CI 33.0-76.0%); median PFS was 4.23 months (95% CI 2.8-11.7). No treatment-related decrease in Tregs was observed. However, elevated baseline levels of Naïve Tregs [greater than 2.5 (the median of the naïve Tregs)] were associated with relative risk of disease progression or death [hazard ratio 11.46 (95% CI 2.32-56.5)]. In addition, the baseline levels of Naïve Tregs (adj-p = 0.04), Memory Tregs (adj-p = 0.003), CD4 + Central Memory T cells (adj-p = 0.0004), PD-1 + CD4 + Central Memory T cells (adj-p = 0.008), and PD-1 + CD4 + Effector Memory T cells (adj-p = 0.009) were significantly greater in the patients than in the healthy controls; the baseline levels of  %CD4 + Naïve T cells (adj-p = 0.0004) were significantly lower in patients compared with healthy controls (n = 40).
    Conclusion: Treg depletion was not observed with low-dose cyclophosphamide when assessed by the specific marker FOXP3 + Helios +; however, baseline naïve Tregs were associated with 3-month PFS. Exemestane/cyclophosphamide combination had favorable safety profile with evidence of clinical activity in heavily pretreated patients.
    MeSH term(s) Administration, Oral ; Adult ; Aged ; Androstadienes/pharmacology ; Androstadienes/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/immunology ; Breast/pathology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Cyclophosphamide/pharmacology ; Cyclophosphamide/therapeutic use ; Disease Progression ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/immunology ; Female ; Humans ; Middle Aged ; Postmenopause ; Progression-Free Survival ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Androstadienes ; Biomarkers, Tumor ; Receptors, Estrogen ; Receptors, Progesterone ; Cyclophosphamide (8N3DW7272P) ; exemestane (NY22HMQ4BX)
    Language English
    Publishing date 2017-11-09
    Publishing country Netherlands
    Document type Clinical Trial, Phase II ; Journal Article
    ZDB-ID 604563-7
    ISSN 1573-7217 ; 0167-6806
    ISSN (online) 1573-7217
    ISSN 0167-6806
    DOI 10.1007/s10549-017-4570-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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