Biology DivisionLaboratory of Microbiology

Research Outline

In our laboratory, with the aim of developing newly effective antibiotics active against globally problematic anti-microbial resistant (AMR) bacteria, we are search for lead compounds from microbial metabolites by using our own unique and original screening systems. We then focus on revealing the mode of action of the obtained novel leads, and in cooperation with other departments, create much more favorable compounds using organic synthesis approaches for the purpose of refinement of new drug candidates.

In addition to the above, our laboratory is building up a microbial library with high originality as a source of diverse compounds by eagerly looking for and collecting new and rare beneficial microorganisms from nature.

If you would like to collaborate, please contact the section of intellectual property and public relations ().

Members

  • PHOTOGRAPH

    Laboratory Head Masayuki Igarashi

  • PHOTOGRAPH

    Chief Researcher Hideyuki Muramatsu

  • PHOTOGRAPH

    Senior Researcher Hideki Hashizume

  • PHOTOGRAPH

    Senior Researcher Yoshimasa Ishizaki

Number of Members 20

Themes

  1. Libraries; Microbes, Culture broth and Chemicals
  2. Discovery of new antibiotics for drug-resistant strains
  3. Mode of action study of novel antibiotics
  4. Large scale fermenter, filtration device and evaporator

Theme outlines

1. Libraries; Microbes, Culture broth and Chemicals

<Microbial library>
We are collecting actinomycetes from soil, fallen leaves, marine sediments and insects all over Japan. Collected isolates are characterized by morphology and/or 16S rRNA gene sequence phylogeny. We also collect non-actinomycete bacteria and filamentous fungi other than actinomycetes.

Actinomycetes and other bacteria ca. 40,000 strains (Partial 16S rRNA gene sequenced: ca. 5,000 strains)
Filamentous fungi ca. 5,000 strains (D1/D2 region of 28S rRNA gene sequenced: ca. 3,600 strains)

<Culture broth library>

Actinomycetes and other bacteria ca. 24,000 samples
Filamentous fungi ca. 500 samples

<Chemical library>

Natural products and related compounds ca. 12,500
Chemically synthesized compounds ca. 4,500
Commercially available compounds ca. 30,000
Actinomycetes and other bacteria
ca. 40,000 strains (Partial 16S rRNA gene sequenced: ca. 5,000 strains)
Filamentous fungi
ca. 5,000 strains (D1/D2 region of 28S rRNA gene sequenced: ca. 3,600 strains)

<Culture broth library>

Actinomycetes and other bacteria
ca. 24,000 samples
Filamentous fungi
ca. 500 samples

<Chemical library>

Natural products and related compounds
ca. 12,500
Chemically synthesized compounds
ca. 4,500
Commercially available compounds
ca. 30,000

In the case of collaboration, please contact the section of intellectual property and public relations ().
Link:Photograph of actinomycetes(Colonies on agar mediaElectron micrograph

Left, Actinomycete isolates; center, cultivation of actinomycetes strains; right, Library of the culture broth.

2. Discovery of new antibiotics for drug-resistant strains

It is said that the post-antibiotic era is coming. Many conventional antibiotics are no longer effective and more pathogenic bacteria obtain resistance against the antibiotics that have been labelled “the last resort”.

As a response to this tough situation, we have been exploring novel antibiotics against the pathogens listed below. To provide compounds which meet the clinical needs, we are continually collecting clinically isolated pathogens. We have up to 2,000 clinical isolates and lab strains in total. If necessary, we can also construct genetically modified strains.

・Multidrug-resistant Gram-negative bacteria

Acinetobacter baumannii, Pseudomonas aeruginosa
Carbapenem-resistant Enterobacteriaceae (CRE)

・Drug-resistant Neisseria gonorrhoeae
・Drug-resistant mycobacteria

Mycobacterium tuberculosis (MDR-TB, XDR-TB),
M. avium/intracellulare (MAC), M. abscessus

・Drug-resistant Gram-positive bacteria

Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-Resistant Enterococci  (VRE)

Antimicrobial susceptibility testing for the exploration of novel antibiotics.

3. Mode of action study of novel antibiotics

Considering the widespread problem of AMR pathogenic bacteria, we understand that drugs with unknown mechanisms of action are unacceptable for clinical use. We start the mechanism of action study in the initial phase of development for promising candidates.

Mode of action study of novel antibiotics.

Mechanism of action of antibiotics isolated/developed at IMC

ZOOM
Mechanism of action of antibiotics isolated/developed at IMC

4. Large scale fermenter, filtration device and evaporator

・Gram or kilogram scale production of natural compounds for pre-clinical research are performed with large scale fermenters and other equipment.

<Large scale fermenter>
・Fermentation tank VE1000 600L (B.E.MARUBISHI CO.,LTD.)
・Fermentation tank MPF-U3 200L (B.E.MARUBISHI CO.,LTD.)
・Jar fermenter MSJ-U3 30L 2 jars (B.E.MARUBISHI CO.,LTD.)

<Large scale filtration device>
・Filter press FP-25S-CL (Cosmic Mechanical Technology. co.,ltd.)
・Ceramic filter filtration machine SA453K (NIHON ROSUIKI KOGYO CO.,Ltd)

<Large scale evaporator>
・Rotary vacuum evaporator N-21 (EYELA)
・Thin film flash evapolator F-70 (EYELA)

<Freeze Dryer>
・Freezemobile Freeze Dryers FM-25-EL-VP (SP Scientific)

Fermentation tank with a capacity of 600L.

If you would like to collaborate, please contact the section of intellectual property and public relations. ().

Appendix    Diversity of actinomycete morphology

Actinomycete colonies on agar media

Actinomycetes colonies on the agar plates.

Electron micrographs of actinomycetes

Electron micrograph of actinomycete strains.