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Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia

Central nervous system (CNS) melioidosis caused by Burkholderia pseudomallei is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of B. pseudomallei pathogenesis in the CNS needs to be intensively investigated to develo...

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Autores principales: Lohitthai, Sanisa, Rungruengkitkun, Amporn, Jitprasutwit, Niramol, Kong-Ngoen, Thida, Duangurai, Taksaon, Tandhavanant, Sarunporn, Sukphopetch, Passanesh, Chantratita, Narisara, Indrawattana, Nitaya, Pumirat, Pornpan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669256/
https://www.ncbi.nlm.nih.gov/pubmed/38001928
http://dx.doi.org/10.3390/biomedicines11112927
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author Lohitthai, Sanisa
Rungruengkitkun, Amporn
Jitprasutwit, Niramol
Kong-Ngoen, Thida
Duangurai, Taksaon
Tandhavanant, Sarunporn
Sukphopetch, Passanesh
Chantratita, Narisara
Indrawattana, Nitaya
Pumirat, Pornpan
author_facet Lohitthai, Sanisa
Rungruengkitkun, Amporn
Jitprasutwit, Niramol
Kong-Ngoen, Thida
Duangurai, Taksaon
Tandhavanant, Sarunporn
Sukphopetch, Passanesh
Chantratita, Narisara
Indrawattana, Nitaya
Pumirat, Pornpan
author_sort Lohitthai, Sanisa
collection PubMed
description Central nervous system (CNS) melioidosis caused by Burkholderia pseudomallei is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of B. pseudomallei 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 B. pseudomallei 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 B. pseudomallei tagAB-5 mutant and complementary strains by the markerless allele replacement method. The effects of tagAB-5 deletion on the pathogenicity of B. pseudomallei were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the tagAB-5 mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the tagAB-5 mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of B. pseudomallei is required for IL-8 production in microglia. However, no significant differences in virulence in the Galleria mellonella model were observed between the tagAB-5 mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for B. pseudomallei, particularly in CNS infection, and TagAB-5 confers B. pseudomallei pathogenicity in these cells.
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spelling pubmed-106692562023-10-30 Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia Lohitthai, Sanisa Rungruengkitkun, Amporn Jitprasutwit, Niramol Kong-Ngoen, Thida Duangurai, Taksaon Tandhavanant, Sarunporn Sukphopetch, Passanesh Chantratita, Narisara Indrawattana, Nitaya Pumirat, Pornpan Biomedicines Article Central nervous system (CNS) melioidosis caused by Burkholderia pseudomallei is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of B. pseudomallei 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 B. pseudomallei 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 B. pseudomallei tagAB-5 mutant and complementary strains by the markerless allele replacement method. The effects of tagAB-5 deletion on the pathogenicity of B. pseudomallei were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the tagAB-5 mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the tagAB-5 mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of B. pseudomallei is required for IL-8 production in microglia. However, no significant differences in virulence in the Galleria mellonella model were observed between the tagAB-5 mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for B. pseudomallei, particularly in CNS infection, and TagAB-5 confers B. pseudomallei pathogenicity in these cells. MDPI 2023-10-30 /pmc/articles/PMC10669256/ /pubmed/38001928 http://dx.doi.org/10.3390/biomedicines11112927 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lohitthai, Sanisa
Rungruengkitkun, Amporn
Jitprasutwit, Niramol
Kong-Ngoen, Thida
Duangurai, Taksaon
Tandhavanant, Sarunporn
Sukphopetch, Passanesh
Chantratita, Narisara
Indrawattana, Nitaya
Pumirat, Pornpan
Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title_full Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title_fullStr Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title_full_unstemmed Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title_short Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
title_sort type vi secretion system accessory protein tagab-5 promotes burkholderia pseudomallei pathogenicity in human microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669256/
https://www.ncbi.nlm.nih.gov/pubmed/38001928
http://dx.doi.org/10.3390/biomedicines11112927
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