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Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition

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Acarbose May Function as a Competitive Exclusion Agent for the Producing Bacteria.

Samuel Tanoeyadi¹, Takeshi Tsunoda¹, Takuya Ito²

¹Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon 97331-3507, United States.

ACS Chemical Biology

|January 17, 2023

Summary

Acarbose, used for diabetes, is produced by bacteria as a weapon to inhibit competitors. These bacteria possess resistant enzymes, allowing them to thrive while others are suppressed.

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Area of Science:

Microbiology
Biochemistry
Natural Products

Background:

Acarbose is a pseudo-oligosaccharide (PsOS) clinically used for type 2 diabetes.
PsOSs inhibit glycosyl hydrolases like α-glucosidases and α-amylases.
The ecological role of PsOSs in microbial communities remains unclear.

Purpose of the Study:

Investigate the ecological role of acarbose and other PsOSs.
Determine the mechanism of resistance to acarbose in producing bacteria.
Understand the competitive interactions mediated by acarbose in microbial environments.

Main Methods:

Culturing PsOS-producing and non-producing actinobacteria with acarbose.
Enzyme inhibition assays using recombinant α-amylases.
Bioinformatic analysis and protein modeling of α-amylase variants.

Main Results:

PsOS-producing bacteria grew in the presence of acarbose, while non-producers' growth was suppressed.
α-amylases from PsOS-producers were resistant to acarbose, unlike those from non-producers.
A point mutation in PsOS-producer α-amylases conferred acarbose resistance.

Conclusions:

Acarbose functions as a competitive exclusion agent against non-producing microbes.
Producing bacteria evolve resistant α-amylases for self-protection.
This highlights a microbial strategy for niche dominance and resource acquisition.