Academic Journal
Inactivation of the Sts enzymes promotes resistance to lethal Staphylococcus aureus infection
| العنوان: | Inactivation of the Sts enzymes promotes resistance to lethal Staphylococcus aureus infection |
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| المؤلفون: | Zaman, Anika, Diago Navarro, Elizabeth, Fries, Bettina C., Kim, Hwan Keun, Carpino, Nick |
| المساهمون: | Torres, Victor J., HHS | NIH | National Institute of Allergy and Infectious Diseases, SUNY | Stony Brook University |
| المصدر: | Infection and Immunity ; volume 91, issue 10 ; ISSN 0019-9567 1098-5522 |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2023 |
| الوصف: | Staphylococcus aureus is a highly infective Gram-positive bacterial pathogen that causes a wide range of diseases in both healthy and immunocompromised individuals. It can evade host immune defenses by expressing numerous virulence factors and toxins. Coupled with the inability of the human host to develop protective immunity against S. aureus , the emergence of antibiotic-resistant strains complicates treatment options. The non-canonical Sts phosphatases negatively regulate signaling pathways in varied immune cell types. To determine the role of the Sts proteins in regulating host responses to a Gram-positive microorganism, we investigated the response of mice lacking Sts expression to S. aureus infection. Herein, we demonstrate that Sts −/− animals are significantly resistant to lethal intravenous doses of S. aureus strain USA300. Resistance is characterized by significantly enhanced survival and accelerated bacterial clearance in multiple peripheral organs. Infected Sts −/− animals do not display increased levels of cytokines TNFα, IFNγ, and IL-6 in the spleen, liver, and kidney during the early stages of the infection, suggesting that a heightened pro-inflammatory response does not underlie the resistance phenotype. In vivo ablation of mononuclear phagocytes compromises the Sts −/− enhanced CFU clearance phenotype. Additionally, Sts −/− bone marrow-derived macrophages demonstrate significantly enhanced restriction of intracellular S. aureus following ex vivo infection. These results reveal the Sts enzymes to be critical regulators of host immunity to a virulent Gram-positive pathogen and identify them as therapeutic targets for optimizing host anti-microbial responses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1128/iai.00260-23 |
| الاتاحة: | http://dx.doi.org/10.1128/iai.00260-23 https://journals.asm.org/doi/pdf/10.1128/iai.00260-23 |
| Rights: | https://doi.org/10.1128/ASMCopyrightv2 ; https://journals.asm.org/non-commercial-tdm-license |
| رقم الانضمام: | edsbas.B120A6C4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/iai.00260-23 |
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