Hiroshi HamamotoPh.D.

Academic Society Affiliations

American Society for Microbiology
The Japanese Society of Chemotherapy
The Japanese Society of Bacteriology
The Japanese Society of Medical Mycology
The Pharmaceutical Society of Japan

Academic Society Activities

Drug Discovery and Therapeutics誌, Associate Editor
Antibiotics, Associate Editor

Research Themes

1. Analysis of the mechanism of action of Lysocin E and research on its practical application

We are currently engaged in research focused on the development of Lysocin E, an antibiotic produced by bacteria isolated from the soil of Okinawa. Lysocin E shows great potential as a treatment for recalcitrant MRSA infections. Our exploration of Lysocin E was based on evaluating its therapeutic efficacy using a silkworm model infected with Staphylococcus aureus (Publication 14). This unique antibiotic has a distinctive mechanism of action and has demonstrated high therapeutic efficacy due to its antimicrobial activity, which is enhanced by apolipoproteins A-I and II in the serum (Publication 3). Notably, Lysocin E exhibits more potent bactericidal activity against Staphylococcus aureus than other anti-MRSA drugs, achieving a bactericidal rate of over 99.9% within just one minute. Our ongoing research aims to uncover the underlying mechanism responsible for this remarkable bactericidal activity. Additionally, we are actively involved in the development of Lysocin E for future clinical trials.

In addition, Lysocin E alone is insufficient to combat antimicrobial-resistant bacteria. We are actively engaged in the discovery of new antibiotics and the analysis of their mechanisms of action. While we are unable to disclose specific details due to patent problems, we anticipate that this research will make a substantial contribution to strategies aimed at combating drug-resistant bacteria.

2. Analysis of pathogenic mechanisms of bacteria and fungi

To gain insights into how bacteria and fungi manifest their virulence in the host environment, we are conducting comprehensive expression analysis using next-generation sequencers (Publication 2). This research has unveiled certain phenomena that challenge previously established knowledge. Moreover, by employing a comprehensive gene disruptant library, we have successfully identified strains that exhibit reduced virulence in silkworm infection models, allowing us to delve into the elucidation of novel mechanisms of virulence expression (Publication 5, 7). These investigations serve as the basis for developing new drugs that target metabolic mechanisms associated with pathogenicity, despite their lack of involvement in in vitro growth.

Contact E-mail address

E-mail: hamamoto★
Please convert "★" to "@".

Featured Publications

See Research Map‪ or Google Scholarfor all achievements

1. Geberetsadik G, Inaizumi A, Nishiyama A, Yamaguchi T, Hamamoto H, Panthee S, Tamaru A, Hayatsu M, Mizutani Y, Kaboso S A, Hakamata M, Ilinov A, Ozeki Y, Tateishi Y, Sekimizu K, Matsumoto S: Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs, Antimicrob Agents Chemother, 66, e0017122, 2022

2. Hamamoto H, Panthee S, Paudel A, Ohgi S, Suzuki Y, Makimura K, Sekimizu K: Transcriptome change of Staphylococcus aureus in infected mouse liver, Commun Biol, 5, 721, 2022

3. Hamamoto H, Panthee S, Paudel A, Ishii K, Yasukawa J, Su J, Miyashita A, Itoh H, Tokumoto K, Inoue M, Sekimizu K: Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus, Nat Commun, 12, 6364, 2021

4. Panthee S, Hamamoto H, Nishiyama Y, Paudel A, Sekimizu K: Novel pathogenic mucorales identified using the silkworm infection model, J Fungi (Basel), 7, 995, 2021

5. Paudel A, Panthee S, Hamamoto H, Grunert T, Sekimizu K: YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus, Virulence, 12, 470-480, 2021

6. Panthee S, Paudel A, Hamamoto H, Uhlemann A C, Sekimizu K: The role of amino acid substitution in HepT toward menaquinone isoprenoid chain length definition and lysocin E sensitivity in Staphylococcus aureus, Front Microbiol, 11, 2076, 2020

7. Paudel A, Hamamoto H, Panthee S, Matsumoto Y, Sekimizu K: Large-scale screening and identification of novel pathogenic Staphylococcus aureus genes using a silkworm infection model, J Infect Dis, 221, 1795-1804, 2020

8. Takada Y, Itoh H, Paudel A, Panthee S, Hamamoto H, Sekimizu K, Inoue M: Discovery of gramicidin A analogues with altered activities by multidimensional screening of a one-bead-one-compound library, Nat Commun, 11, 4935, 2020

9. Itoh H, Tokumoto K, Kaji T, Paudel A, Panthee S, Hamamoto H, Sekimizu K, Inoue M: Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E, Nat Commun, 10, 2992, 2019

10. Panthee S, Paudel A, Hamamoto H, Sekimizu K: Complete genome sequence of Weissella hellenica 0916-4-2 and its comparative genomic analysis, Front Microbiol, 10, 1619, 2019

11. Panthee S, Paudel A, Hamamoto H, Sekimizu K: Advantages of the silkworm as an animal model for developing novel antimicrobial agents, Front Microbiol, 8, 373, 2017

12. Paudel A, Hamamoto H, Panthee S, Kaneko K, Matsunaga S, Kanai M, Suzuki Y, Sekimizu K: A novel spiro-heterocyclic compound identified by the silkworm infection model inhibits transcription in Staphylococcus aureus, Front Microbiol, 8, 712, 2017

13. Kaji T, Murai M, Itoh H, Yasukawa J, Hamamoto H, Sekimizu K, Inoue M: Total synthesis and functional evaluation of fourteen derivatives of lysocin E: importance of cationic, hydrophobic, and aromatic moieties for antibacterial activity, Chem Eur J, 22, 16912-16919, 2016

14. Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, Kaji T, Kuranaga T, Hamase K, Katsu T, Su J, Adachi T, Uchida R, Tomoda H, Yamada M, Souma M, Kurihara H, Inoue M, Sekimizu K: Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane, Nat Chem Biol, 11, 127-133, 2015

15. Murai M, Kaji T, Kuranaga T, Hamamoto H, Sekimizu K, Inoue M: Total synthesis and biological evaluation of the antibiotic lysocin e and its enantiomeric, epimeric, and N-demethylated analogues, Angew Chem Int Ed Engl, 54, 1556-1560, 2015

16. Ishii K, Adachi T, Hamamoto H, Sekimizu K: Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells, J Biol Chem, 289, 5876-5888, 2014

17. Ishii K, Adachi T, Imamura K, Takano S, Usui K, Suzuki K, Hamamoto H, Watanabe T, Sekimizu K: Serratia marcescens induces apoptotic cell death in host immune cells via a lipopolysaccharide- and flagella-dependent mechanism, J Biol Chem, 287, 36582-36592, 2012

18. Ishii K, Hamamoto H, Imamura K, Adachi T, Shoji M, Nakayama K, Sekimizu K: Porphyromonas gingivalis peptidoglycans induce excessive activation of the innate immune system in silkworm larvae, J Biol Chem, 285, 33338-33347, 2010

19. Ishii K, Hamamoto H, Kamimura M, Nakamura Y, Noda H, Imamura K, Mita K, Sekimizu K: Insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori, J Biol Chem, 285, 28635-28642, 2010

20. Kurokawa K, Hamamoto H, Matsuo M, Nishida S, Yamane N, Lee B L, Murakami K, Maki H, Sekimizu K: Evaluation of target specificity of antibacterial agents using Staphylococcus aureus ddlA mutants and D-cycloserine in a silkworm infection model, Antimicrob Agents Chemother, 53, 4025-4027, 2009

21. Ishii K, Hamamoto H, Kamimura M, Sekimizu K: Activation of the silkworm cytokine by bacterial and fungal cell wall components via a reactive oxygen species-triggered mechanism, J Biol Chem, 283, 2185-2191, 2008

22. Orihara Y, Hamamoto H, Kasuga H, Shimada T, Kawaguchi Y, Sekimizu K: A silkworm baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines, J Gen Virol, 89, 188-194, 2008

23. Hamamoto H, Kamura K, Razanajatovo I M, Murakami K, Santa T, Sekimizu K: Effects of molecular mass and hydrophobicity on transport rates through non-specific pathways of the silkworm larva midgut, Int J Antimicrob Agents, 26, 38-42, 2005

24. Hamamoto H, Kurokawa K, Kaito C, Kamura K, Manitra Razanajatovo I, Kusuhara H, Santa T, Sekimizu K: Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms, Antimicrob Agents Chemother, 48, 774-779, 2004

25. Akimitsu N, Hamamoto H, Inoue R, Shoji M, Akamine A, Takemori K, Hamasaki N, Sekimizu K: Increase in resistance of methicillin-resistant Staphylococcus aureus to beta-lactams caused by mutations conferring resistance to benzalkonium chloride, a disinfectant widely used in hospitals, Antimicrob Agents Chemother, 43, 3042-3043, 1999

Return to previous