Development of New Screening Methods to Find Novel Antibiotics
- Many existing antibiotics were originally isolated from soil microbes
- ~99% of environmental bacteria are uncultured and may be a major source of new antibiotics
Teixobactin and iChip
- In 2015, researchers discovered Teixobactin using the iChip screening tool
- iChip enables growth of previously uncultured soil microorganisms in the lab
What does iChip consist of?
- A central plate that houses growing microorganisms
- Semi-permeable membranes on each side of the plate, which separate the plate from the environment
-Two supporting side panels
iChip Method
- Tiny soil bacterial samples are trapped in agar plugs inside the iChip
- The device is returned to the soil so microbes grow in their natural environment
- Enables cultivation of previously unculturable bacteria → new antibiotics (e.g., Teixobactin)
2 strategies to develop new antimicrobial drugs
- Synthesize thousand of compounds in lab and test to see if they inhibit bacterial growth
- Search for pre-existing compounds
Mining Microbial Genomes
- The reduced cost and increased speed of high-throughput sequencing allow scientists to search microbial genomes for useful genes without needing to cultivate the microbes
- This metagenomic approach greatly expands the number of species and gene products that can be screened, avoiding labor-intensive growth experiments
When promising gene targets are found, what are some follow-up analyses?
- molecular biology
- metabolomics
- metabolic engineering
- chemical or enzymatic synthesis
- studying the response of the host or target organism
Mining Microbial Genomes - Example
- Researchers screened 10,000 bacterial strains for a gene involved in phosphonate biosynthesis
- 278 strains contained the target gene → these strains were fully genome-sequenced
- Sequencing revealed additional genes involved in phosphonate biosynthesis
- Further testing showed one specific phosphonate with antimicrobial activity
- This compound may become a new clinically relevant antibiotic
Why studying microorganisms is of value - reason 1
Microorganisms are important sources of knowledge about the strategies and limits of life
Why studying microorganisms is of value - reason 2
Microorganisms are of critical importance to the sustainability of life on our planet
Why studying microorganisms is of value - reason 3
The untapped diversity of microorganisms is a resource for new genes and organisms of value to biotechnology and new medical interventions
Why studying microorganisms is of value - reason 4
Diversity patterns of microorganisms can be used for monitoring and predicting environmental change
Why studying microorganisms is of value - reason 5
Microorganisms play a role in conservation and restoration biology of higher organisms
Why studying microorganisms is of value - reason 6
Microbial communities are excellent models for understanding biological interactions and evolutionary history
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Module 1: Section 124
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Module 1: Section 236
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Module 2: Section 1A26
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Module 2: Section 1B54
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Module 2: Section 1C8
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Module 2: Section 1D7
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Module 2: Section 2A16
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Module 2: Section 2B6
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Module 2: Section 2C5
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Module 2: Section 2D12
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Module 3: Section 1A15
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Module 3: Section 1B19
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Module 3: Section 1C16
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Module 3: Section 2A18
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Module 3: Section 2B22
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Module 3: Section 2C31
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Module 3: Section 2D23
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Module 3: Section 2E14
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Module 4: Section 1A24
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Module 4: Section 1B24
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Module 4: Section 2A15
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Module 4: Section 2B14
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Module 4: Section 3A34
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Module 4: Section 3B31
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Module 4: Section 3C21
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Module 5: Section 1A15
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Module 5: Section 1B9
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Module 5: Section 1C14
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Module 5: Section 2A30
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Module 5: Section 2B13
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Module 5: Section 2C32
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Module 6: Section 1A15
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Module 6: Section 1B24
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Module 6: Section 1C14
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Module 6: Section 2A14
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Module 6: Section 2B32
