Genetic variation of hemolysin co-regulated protein 1 affects the immunogenicity and pathogenicity of Burkholderia pseudomallei
Issued Date
2025-01-01
Resource Type
eISSN
19352735
Scopus ID
2-s2.0-85216135879
Pubmed ID
39761280
Journal Title
PLoS neglected tropical diseases
Volume
19
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS neglected tropical diseases Vol.19 No.1 (2025) , e0012758
Suggested Citation
Tandhavanant S., Yimthin T., Sengyee S., Charoenwattanasatien R., Lebedev A.A., Lafontaine E.R., Hogan R.J., Chewapreecha C., West T.E., Brett P.J., Burtnick M.N., Chantratita N. Genetic variation of hemolysin co-regulated protein 1 affects the immunogenicity and pathogenicity of Burkholderia pseudomallei. PLoS neglected tropical diseases Vol.19 No.1 (2025) , e0012758. doi:10.1371/journal.pntd.0012758 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/104174
Title
Genetic variation of hemolysin co-regulated protein 1 affects the immunogenicity and pathogenicity of Burkholderia pseudomallei
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
University of Georgia
University of Washington School of Medicine
Suranaree University of Technology
Rutherford Appleton Laboratory
University of Washington
Nagasaki University
University of Nevada, Reno School of Medicine
Synchrotron Light Research Institute (Public Organization)
Mahidol Oxford Tropical Medicine Research Unit
University of Georgia
University of Washington School of Medicine
Suranaree University of Technology
Rutherford Appleton Laboratory
University of Washington
Nagasaki University
University of Nevada, Reno School of Medicine
Synchrotron Light Research Institute (Public Organization)
Corresponding Author(s)
Other Contributor(s)
Abstract
Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B. pseudomallei strains, variants of hcp1 have recently been identified. This study aimed to examine the prevalence of hcp1 variants in clinical isolates of B. pseudomallei, assess the antigenicity of the Hcp1 variants, and the ability of strains expressing these variants to stimulate multinucleated giant cell (MNGC) formation in comparison to strains expressing wild-type Hcp1 (Hcp1wt). Sequence analysis of 1,283 primary clinical isolates of B. pseudomallei demonstrated the presence of 8 hcp1 alleles encoding three types of Hcp1 proteins, including Hcp1wt (98.05%), Hcp1variant A (1.87%) and Hcp1variant B (0.08%). Compared to strains expressing Hcp1wt, those expressing the dominant variant, Hcp1variant A, stimulated lower levels of Hcp1variant A-specific antibody responses in melioidosis patients. Interestingly, when Hcp1variant A was expressed in B. pseudomallei K96243, this strain retained the ability to stimulate MNGC formation in A549 cells. In contrast, however, similar experiments with the Hcp1variant B demonstrated a decreased ability of B. pseudomallei to stimulate MNGC formation. Collectively, these results show that B. pseudomallei strains expressing variants of Hcp1 elicit variable antibody responses in melioidosis patients and differ in their ability to promote MNGC formation in cell culture.