Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae
Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucia...
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Elsevier
2025-02-01
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| Series: | Journal of Microbiology, Immunology and Infection |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1684118224001877 |
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| author | Tien-Huang Lin Chen-Yu Wang Chien-Chen Wu Ching-Ting Lin |
| author_facet | Tien-Huang Lin Chen-Yu Wang Chien-Chen Wu Ching-Ting Lin |
| author_sort | Tien-Huang Lin |
| collection | DOAJ |
| description | Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucial. Acetyl-phosphate (AcP) is essential for bacterial metabolism and can affect virulence factor expression. However, the role of the Pta-AckA pathway, which regulates AcP levels, in K. pneumoniae pathogenesis remains unclear. Methods: Deletion mutants lacking the pta and ackA, involved in AcP production and hydrolysis, were generated in K. pneumoniae CG43S3. Their effects on AcP levels, the patterns of global acetylated protein, capsular polysaccharide (CPS) amount, serum resistance, type 3 fimbriae expression, biofilm formation, and virulence in G. mellonella larva were assessed. Results: Deletion of ackA in K. pneumoniae CG43S3 led to AcP accumulation, while pta deletion abolished AcP synthesis when grown in TB7+1 % glucose. This pathway influenced global protein acetylation, with pta deletion decreasing acetylation and ackA deletion increasing it. Additionally, pta deletion decreased the CPS amount, serum resistance, and type 3 fimbriae expression, while ackA deletion increased these factors. Furthermore, deleting pta and ackA attenuated the infected larva's virulence and death rate. Conclusion: Our findings highlight the critical role of the Pta-AckA pathway in K. pneumoniae pathogenesis. This pathway regulates AcP levels, global protein acetylation, CPS production, serum resistance, and type 3 fimbriae expression, ultimately impacting virulence. The information provides insights into potential therapeutic targets for combating K. pneumoniae infection. |
| format | Article |
| id | doaj-art-d65657d89883499f93bbca7049dd26de |
| institution | Kabale University |
| issn | 1684-1182 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Microbiology, Immunology and Infection |
| spelling | doaj-art-d65657d89883499f93bbca7049dd26de2025-02-06T05:11:20ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822025-02-015814855Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniaeTien-Huang Lin0Chen-Yu Wang1Chien-Chen Wu2Ching-Ting Lin3Department of Urology, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, TaiwanGraduate Institute of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hsinchu Hospital, Hsinchu, TaiwanInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, TaiwanGraduate Institute of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Corresponding author. School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Rd, Taichung, 40402, Taiwan.Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucial. Acetyl-phosphate (AcP) is essential for bacterial metabolism and can affect virulence factor expression. However, the role of the Pta-AckA pathway, which regulates AcP levels, in K. pneumoniae pathogenesis remains unclear. Methods: Deletion mutants lacking the pta and ackA, involved in AcP production and hydrolysis, were generated in K. pneumoniae CG43S3. Their effects on AcP levels, the patterns of global acetylated protein, capsular polysaccharide (CPS) amount, serum resistance, type 3 fimbriae expression, biofilm formation, and virulence in G. mellonella larva were assessed. Results: Deletion of ackA in K. pneumoniae CG43S3 led to AcP accumulation, while pta deletion abolished AcP synthesis when grown in TB7+1 % glucose. This pathway influenced global protein acetylation, with pta deletion decreasing acetylation and ackA deletion increasing it. Additionally, pta deletion decreased the CPS amount, serum resistance, and type 3 fimbriae expression, while ackA deletion increased these factors. Furthermore, deleting pta and ackA attenuated the infected larva's virulence and death rate. Conclusion: Our findings highlight the critical role of the Pta-AckA pathway in K. pneumoniae pathogenesis. This pathway regulates AcP levels, global protein acetylation, CPS production, serum resistance, and type 3 fimbriae expression, ultimately impacting virulence. The information provides insights into potential therapeutic targets for combating K. pneumoniae infection.http://www.sciencedirect.com/science/article/pii/S1684118224001877Klebsiella pneumoniaeAcetyl-phosphatePta-AckA pathwayCapsular polysaccharideType 3 fimbriae |
| spellingShingle | Tien-Huang Lin Chen-Yu Wang Chien-Chen Wu Ching-Ting Lin Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae Journal of Microbiology, Immunology and Infection Klebsiella pneumoniae Acetyl-phosphate Pta-AckA pathway Capsular polysaccharide Type 3 fimbriae |
| title | Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae |
| title_full | Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae |
| title_fullStr | Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae |
| title_full_unstemmed | Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae |
| title_short | Impacts of Pta-AckA pathway on CPS biosynthesis and type 3 fimbriae expression in Klebsiella pneumoniae |
| title_sort | impacts of pta acka pathway on cps biosynthesis and type 3 fimbriae expression in klebsiella pneumoniae |
| topic | Klebsiella pneumoniae Acetyl-phosphate Pta-AckA pathway Capsular polysaccharide Type 3 fimbriae |
| url | http://www.sciencedirect.com/science/article/pii/S1684118224001877 |
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