Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia
Central nervous system (CNS) melioidosis caused by <i>Burkholderia pseudomallei</i> is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of <i>B. pseudomallei</i> pathogenesis in the CNS needs to...
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MDPI AG
2023-10-01
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| author | Sanisa Lohitthai Amporn Rungruengkitkun Niramol Jitprasutwit Thida Kong-Ngoen Taksaon Duangurai Sarunporn Tandhavanant Passanesh Sukphopetch Narisara Chantratita Nitaya Indrawattana Pornpan Pumirat |
| author_facet | Sanisa Lohitthai Amporn Rungruengkitkun Niramol Jitprasutwit Thida Kong-Ngoen Taksaon Duangurai Sarunporn Tandhavanant Passanesh Sukphopetch Narisara Chantratita Nitaya Indrawattana Pornpan Pumirat |
| author_sort | Sanisa Lohitthai |
| collection | DOAJ |
| description | Central nervous system (CNS) melioidosis caused by <i>Burkholderia pseudomallei</i> is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of <i>B. pseudomallei</i> pathogenesis in the CNS needs to be intensively investigated to develop better therapeutic strategies against this deadly disease. The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells to benefit the infection process. In this study, the role of the T6SS accessory protein TagAB-5 in <i>B. pseudomallei</i> pathogenicity was examined using the human microglial cell line HCM3, a unique resident immune cell of the CNS acting as a primary mediator of inflammation. We constructed <i>B. pseudomallei tagAB-5</i> mutant and complementary strains by the markerless allele replacement method. The effects of <i>tagAB-5</i> deletion on the pathogenicity of <i>B. pseudomallei</i> were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the <i>tagAB-5</i> mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the <i>tagAB-5</i> mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of <i>B. pseudomallei</i> is required for IL-8 production in microglia. However, no significant differences in virulence in the <i>Galleria mellonella</i> model were observed between the <i>tagAB-5</i> mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for <i>B. pseudomallei,</i> particularly in CNS infection, and TagAB-5 confers <i>B. pseudomallei</i> pathogenicity in these cells. |
| first_indexed | 2024-03-09T17:00:51Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T17:00:51Z |
| publishDate | 2023-10-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b042f8c8c877475598d047a9face80ce2023-11-24T14:30:46ZengMDPI AGBiomedicines2227-90592023-10-011111292710.3390/biomedicines11112927Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human MicrogliaSanisa Lohitthai0Amporn Rungruengkitkun1Niramol Jitprasutwit2Thida Kong-Ngoen3Taksaon Duangurai4Sarunporn Tandhavanant5Passanesh Sukphopetch6Narisara Chantratita7Nitaya Indrawattana8Pornpan Pumirat9Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandCenter for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Companion Animal Clinical Sciences, Kasetsart University, Bangkok 10900, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, ThailandCentral nervous system (CNS) melioidosis caused by <i>Burkholderia pseudomallei</i> is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of <i>B. pseudomallei</i> pathogenesis in the CNS needs to be intensively investigated to develop better therapeutic strategies against this deadly disease. The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells to benefit the infection process. In this study, the role of the T6SS accessory protein TagAB-5 in <i>B. pseudomallei</i> pathogenicity was examined using the human microglial cell line HCM3, a unique resident immune cell of the CNS acting as a primary mediator of inflammation. We constructed <i>B. pseudomallei tagAB-5</i> mutant and complementary strains by the markerless allele replacement method. The effects of <i>tagAB-5</i> deletion on the pathogenicity of <i>B. pseudomallei</i> were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the <i>tagAB-5</i> mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the <i>tagAB-5</i> mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of <i>B. pseudomallei</i> is required for IL-8 production in microglia. However, no significant differences in virulence in the <i>Galleria mellonella</i> model were observed between the <i>tagAB-5</i> mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for <i>B. pseudomallei,</i> particularly in CNS infection, and TagAB-5 confers <i>B. pseudomallei</i> pathogenicity in these cells.https://www.mdpi.com/2227-9059/11/11/2927<i>Burkholderia pseudomallei</i>neuropathogenesistype VI secretion system<i>Galleria mellonella</i> |
| spellingShingle | Sanisa Lohitthai Amporn Rungruengkitkun Niramol Jitprasutwit Thida Kong-Ngoen Taksaon Duangurai Sarunporn Tandhavanant Passanesh Sukphopetch Narisara Chantratita Nitaya Indrawattana Pornpan Pumirat Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia Biomedicines <i>Burkholderia pseudomallei</i> neuropathogenesis type VI secretion system <i>Galleria mellonella</i> |
| title | Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia |
| title_full | Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia |
| title_fullStr | Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia |
| title_full_unstemmed | Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia |
| title_short | Type VI Secretion System Accessory Protein TagAB-5 Promotes <i>Burkholderia pseudomallei</i> Pathogenicity in Human Microglia |
| title_sort | type vi secretion system accessory protein tagab 5 promotes i burkholderia pseudomallei i pathogenicity in human microglia |
| topic | <i>Burkholderia pseudomallei</i> neuropathogenesis type VI secretion system <i>Galleria mellonella</i> |
| url | https://www.mdpi.com/2227-9059/11/11/2927 |
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