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  1. Article ; Online: Staphylococcus aureus: The Bug Behind the Itch in Atopic Dermatitis.

    Gallo, Richard L / Horswill, Alexander R

    The Journal of investigative dermatology

    2024  Volume 144, Issue 5, Page(s) 950–953

    Abstract: Pruritus or itch is a defining symptom of atopic dermatitis (AD). The origins of itch are complex, and it is considered both a defense mechanism and a cause of disease that leads to inflammation and psychological stress. Considerable progress has been ... ...

    Abstract Pruritus or itch is a defining symptom of atopic dermatitis (AD). The origins of itch are complex, and it is considered both a defense mechanism and a cause of disease that leads to inflammation and psychological stress. Considerable progress has been made in understanding the processes that trigger itch, particularly the pruritoceptive origins that are generated in the skin. This perspective review discusses the implications of a recent observation that the V8 protease expressed by Staphylococcus aureus can directly trigger sensory neurons in the skin through activation of protease-activated receptor 1. This may be a key to understanding why itch is so common in AD because S. aureus commonly overgrows in this disease owing to deficient antimicrobial defense from both the epidermis and the cutaneous microbiome. Increased understanding of the role of microbes in AD provides increased opportunities for safely improving the treatment of this disorder.
    MeSH term(s) Dermatitis, Atopic/microbiology ; Dermatitis, Atopic/complications ; Dermatitis, Atopic/immunology ; Humans ; Pruritus/microbiology ; Pruritus/immunology ; Staphylococcus aureus ; Animals ; Skin/microbiology ; Skin/pathology ; Sensory Receptor Cells/physiology ; Sensory Receptor Cells/metabolism ; Receptors, Proteinase-Activated/metabolism ; Staphylococcal Infections/complications ; Staphylococcal Infections/microbiology
    Chemical Substances Receptors, Proteinase-Activated
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2024.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The role of human extracellular matrix proteins in defining Staphylococcus aureus biofilm infections.

    Bhattacharya, Mohini / Horswill, Alexander R

    FEMS microbiology reviews

    2024  Volume 48, Issue 1

    Abstract: Twenty to forty one percent of the world's population is either transiently or permanently colonized by the Gram-positive bacterium, Staphylococcus aureus. In 2017, the CDC designated methicillin-resistant S. aureus (MRSA) as a serious threat, reporting ∼ ...

    Abstract Twenty to forty one percent of the world's population is either transiently or permanently colonized by the Gram-positive bacterium, Staphylococcus aureus. In 2017, the CDC designated methicillin-resistant S. aureus (MRSA) as a serious threat, reporting ∼300 000 cases of MRSA-associated hospitalizations annually, resulting in over 19 000 deaths, surpassing that of HIV in the USA. S. aureus is a proficient biofilm-forming organism that rapidly acquires resistance to antibiotics, most commonly methicillin (MRSA). This review focuses on a large group of (>30) S. aureus adhesins, either surface-associated or secreted that are designed to specifically bind to 15 or more of the proteins that form key components of the human extracellular matrix (hECM). Importantly, this includes hECM proteins that are pivotal to the homeostasis of almost every tissue environment [collagen (skin), proteoglycans (lung), hemoglobin (blood), elastin, laminin, fibrinogen, fibronectin, and fibrin (multiple organs)]. These adhesins offer S. aureus the potential to establish an infection in every sterile tissue niche. These infections often endure repeated immune onslaught, developing into chronic, biofilm-associated conditions that are tolerant to ∼1000 times the clinically prescribed dose of antibiotics. Depending on the infection and the immune response, this allows S. aureus to seamlessly transition from colonizer to pathogen by subtly manipulating the host against itself while providing the time and stealth that it requires to establish and persist as a biofilm. This is a comprehensive discussion of the interaction between S. aureus biofilms and the hECM. We provide particular focus on the role of these interactions in pathogenesis and, consequently, the clinical implications for the prevention and treatment of S. aureus biofilm infections.
    MeSH term(s) Humans ; Staphylococcus aureus ; Methicillin-Resistant Staphylococcus aureus ; Extracellular Matrix Proteins ; Biofilms ; Anti-Bacterial Agents ; Staphylococcal Infections/microbiology
    Chemical Substances Extracellular Matrix Proteins ; Anti-Bacterial Agents
    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 283740-7
    ISSN 1574-6976 ; 0168-6445
    ISSN (online) 1574-6976
    ISSN 0168-6445
    DOI 10.1093/femsre/fuae002
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  3. Article ; Online: Staphylococcus aureus.

    Keim, Klara C / Horswill, Alexander R

    Trends in microbiology

    2023  Volume 31, Issue 12, Page(s) 1300–1301

    MeSH term(s) Humans ; Staphylococcus aureus/genetics ; Staphylococcal Infections
    Language English
    Publishing date 2023-07-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 1158963-2
    ISSN 1878-4380 ; 0966-842X
    ISSN (online) 1878-4380
    ISSN 0966-842X
    DOI 10.1016/j.tim.2023.07.001
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    Zs.A 3738: Show issues Location:
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  4. Article ; Online: Breaking bad.

    Bhattacharya, Mohini / Horswill, Alexander R

    The Journal of experimental medicine

    2023  Volume 220, Issue 6

    Abstract: DNASE1 (D1) and DNASE1L3 (D1L3) synergistically reduce the severity of systemic infections caused by Staphylococcus aureus. In this issue of JEM, Lacey et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221086) develop D1-/-, D1L3-/-, and D1-/-D1L3-/ ...

    Abstract DNASE1 (D1) and DNASE1L3 (D1L3) synergistically reduce the severity of systemic infections caused by Staphylococcus aureus. In this issue of JEM, Lacey et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221086) develop D1-/-, D1L3-/-, and D1-/-D1L3-/- mice to show that exogenous addition of the DNase formulation Dornase alfa can facilitate removal of biofilms.
    MeSH term(s) Mice ; Animals ; Endodeoxyribonucleases
    Chemical Substances Dnase1l3 protein, mouse (EC 3.1.-) ; Endodeoxyribonucleases (EC 3.1.-)
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20230421
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    Zs.MG 45: Show issues

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  5. Article ; Online: The

    Costa, Flavia G / Mills, Krista B / Crosby, Heidi A / Horswill, Alexander R

    mBio

    2024  , Page(s) e0045324

    Abstract: Staphylococcus aureus: Importance: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    Importance: Staphylococcus aureus
    Language English
    Publishing date 2024-03-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00453-24
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  6. Article ; Online: Overcoming pH defenses on the skin to establish infections.

    Costa, Flavia G / Horswill, Alexander R

    PLoS pathogens

    2022  Volume 18, Issue 5, Page(s) e1010512

    Abstract: Skin health is influenced by the composition and integrity of the skin barrier. The healthy skin surface is an acidic, hypertonic, proteinaceous, and lipid-rich environment that microorganisms must adapt to for survival, and disruption of this ... ...

    Abstract Skin health is influenced by the composition and integrity of the skin barrier. The healthy skin surface is an acidic, hypertonic, proteinaceous, and lipid-rich environment that microorganisms must adapt to for survival, and disruption of this environment can result in dysbiosis and increase risk for infectious diseases. This work provides a brief overview of skin barrier function and skin surface composition from the perspective of how the most common skin pathogen, Staphylococcus aureus, combats acid stress. Advancements in replicating this environment in the laboratory setting for the study of S. aureus pathogenesis on the skin, as well as future directions in this field, are also discussed.
    MeSH term(s) Dysbiosis/pathology ; Humans ; Hydrogen-Ion Concentration ; Skin/pathology ; Staphylococcal Infections/pathology ; Staphylococcus aureus
    Language English
    Publishing date 2022-05-26
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; 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.1010512
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  7. Article ; Online: Staphylococcus epidermidis and its dual lifestyle in skin health and infection.

    Severn, Morgan M / Horswill, Alexander R

    Nature reviews. Microbiology

    2022  Volume 21, Issue 2, Page(s) 97–111

    Abstract: The coagulase-negative bacterium Staphylococcus epidermidis is a member of the human skin microbiota. S. epidermidis is not merely a passive resident on skin but actively primes the cutaneous immune response, maintains skin homeostasis and prevents ... ...

    Abstract The coagulase-negative bacterium Staphylococcus epidermidis is a member of the human skin microbiota. S. epidermidis is not merely a passive resident on skin but actively primes the cutaneous immune response, maintains skin homeostasis and prevents opportunistic pathogens from causing disease via colonization resistance. However, it is now appreciated that S. epidermidis and its interactions with the host exist on a spectrum of potential pathogenicity derived from its high strain-level heterogeneity. S. epidermidis is the most common cause of implant-associated infections and is a canonical opportunistic biofilm former. Additional emerging evidence suggests that some strains of S. epidermidis may contribute to the pathogenesis of common skin diseases. Here, we highlight new developments in our understanding of S. epidermidis strain diversity, skin colonization dynamics and its multifaceted interactions with the host and other members of the skin microbiota.
    MeSH term(s) Humans ; Staphylococcus epidermidis ; Skin/microbiology ; Virulence ; Biofilms ; Microbiota ; Staphylococcal Infections
    Language English
    Publishing date 2022-08-30
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/s41579-022-00780-3
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    Zs.A 5865: Show issues Location:
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    Zs.MG 74: Show issues

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  8. Article: X-ray-driven chemistry and conformational heterogeneity in atomic resolution crystal structures of bacterial dihydrofolate reductases.

    Smith, Nathan / Horswill, Alexander R / Wilson, Mark A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. Bacterial DHFRs are targets of several important antibiotics as well as model enzymes for the role of protein conformational dynamics in enzyme ... ...

    Abstract Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. Bacterial DHFRs are targets of several important antibiotics as well as model enzymes for the role of protein conformational dynamics in enzyme catalysis. We collected 0.93 Å resolution X-ray diffraction data from both
    Language English
    Publishing date 2023-11-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.07.566054
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  9. Article: The

    Costa, Flavia G / Mills, Krista B / Crosby, Heidi A / Horswill, Alexander R

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Staphylococcus aureus: Importance: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    Importance: Staphylococcus aureus
    Language English
    Publishing date 2023-10-24
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.24.563767
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Staphylococcus aureus

    Lyon, Laurie M / Doran, Kelly S / Horswill, Alexander R

    Infection and immunity

    2022  Volume 91, Issue 1, Page(s) e0046022

    Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and frequent colonizer of human skin and mucosal membranes, including the vagina, with vaginal colonization reaching nearly 25% in some pregnant populations. MRSA vaginal ... ...

    Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen and frequent colonizer of human skin and mucosal membranes, including the vagina, with vaginal colonization reaching nearly 25% in some pregnant populations. MRSA vaginal colonization can lead to aerobic vaginitis (AV), and during pregnancy, bacterial ascension into the upper reproductive tract can lead to adverse birth outcomes. USA300, the most prominent MRSA lineage to colonize pregnant individuals, is a robust biofilm former and causative agent of invasive infections; however, little is known about how it colonizes and ascends in the female reproductive tract (FRT). Our previous studies showed that a MRSA mutant of seven fibrinogen-binding adhesins was deficient in FRT epithelial attachment and colonization. Using both monolayer and multilayer air-liquid interface cell culture models, we determine that one class of these adhesins, the fibronectin binding proteins (FnBPA and FnBPB), are critical for association with human vaginal epithelial cells (hVECs) and hVEC invasion through interactions with α
    MeSH term(s) Female ; Humans ; Animals ; Mice ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism ; Methicillin-Resistant Staphylococcus aureus/genetics ; Methicillin-Resistant Staphylococcus aureus/metabolism ; Carrier Proteins/metabolism ; Fibronectins/genetics ; Fibronectins/metabolism ; Adhesins, Bacterial/genetics ; Adhesins, Bacterial/metabolism ; Staphylococcal Infections/microbiology
    Chemical Substances Carrier Proteins ; Fibronectins ; Adhesins, Bacterial
    Language English
    Publishing date 2022-12-13
    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.00460-22
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    Zs.A 684: Show issues Location:
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