Project/Area Number |
21K16947
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 57020:Oral pathobiological science-related
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Research Institution | Hiroshima University |
Principal Investigator |
LE NGUYEN・TRA・MI (レ グエントラミ) 広島大学, 医系科学研究科(歯), 助教 (20897904)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Project Status |
Granted (Fiscal Year 2022)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | Klebsiella pneumoniae / hypervirulent / multidrug resistance / antimicrobial peptide / bacteriocin / hypermucoviscous / string test / antimicrobial resistance / hypervirulence / hypemucoviscosity |
Outline of Research at the Start |
K. pneumoniae has emerged as a global life-threatening pathogen due to the multidrug-resistance and hypervirulence phenotype. My study will investigate the genomic population of clinically-isolated hypermucoviscous (HMV) K. pneumoniae isolates in Japan, the correlation between HMV phenotype, virulence genes, and drug resistance genes, and the novel molecular mechanism of HMV phenotype. This study will improve the predictive model for hypervirulent K. pneumoniae and the development of new chemotherapy targeting the novel virulent factors to improve the treatment outcome of this pathogen.
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Outline of Annual Research Achievements |
Multidrug-resistant and hypervirulent K. pneumoniae has been continuously evolving, which causes severe clinical outcome and significantly challenges the available chemotherapeutic treatment for its infections. K. pneumoniae produces several kinds of antimicrobial peptides known as bacteriocins, which have antibacterial activity against closely-related species. Bacteriocins are considered one of K. pneumoniae virulence factors. We identified bacteriocin genes in 180 K. pneumoniae species complex genomes, including 170 hypermucoviscous isolates, and investigated the antibacterial activity against 50 strains, including antimicrobial-resistant organisms, belonging to multiple species. This study has been accepted on April 11th and published on May 8th in Microbiology Spectrum: Le MN, Nguyen TH, Trinh VM, Nguyen TP, Kawada-Matsuo M, Kayama S, Sugai M, Komatsuzawa H. Comprehensive Analysis of Bacteriocins Produced by the Hypermucoviscous Klebsiella pneumoniae Species Complex. Microbiol Spectr. 2023 May 8:e0086323. doi: 10.1128/spectrum.00863-23. Epub ahead of print. PMID: 37154746.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The first paper has been published in Microbial Genomics in 2022, entitled "Genomic epidemiology and temperature dependency of hypermucoviscous Klebsiella pneumoniae in Japan" (Le MN, Kayama S, Wyres KL, Yu L, Hisatsune J, Suzuki M, Yahara K, Terachi T, Sawa K, Takahashi S, Okuhara T, Kohama K, Holt KE, Mizutani T, Ohge H, Sugai M. Genomic epidemiology and temperature dependency of hypermucoviscous Klebsiella pneumoniae in Japan. Microb Genom. 2022 May;8(5):mgen000827. doi: 10.1099/mgen.0.000827. PMID: 35622495; PMCID: PMC9465067.) The second paper has been published in Microbiology Spectrum in May 8th 2023, entitled "Comprehensive analysis of bacteriocins produced by the hypermucoviscous Klebsiella pneumoniae species complex" (Le MN, Nguyen TH, Trinh VM, Nguyen TP, Kawada-Matsuo M, Kayama S, Sugai M, Komatsuzawa H. Comprehensive Analysis of Bacteriocins Produced by the Hypermucoviscous Klebsiella pneumoniae Species Complex. Microbiol Spectr. 2023 May 8:e0086323. doi: 10.1128/spectrum.00863-23. Epub ahead of print. PMID: 37154746.)
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Strategy for Future Research Activity |
Regarding the hypermucoviscosity (HMV) phenotype, investigation of the novel gene(s) responsible for hypermucoviscosity is being carried out using the isolates with medium/high-HMV phenotype and negative for rmpA and rmpA2 genes. Regarding the bacteriocin theme, we are investigating novel bacteriocins produced by K. pneumoniae to develop potential alternative treatments for infections caused by multidrug-resistant bacteria.
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