Antibiotic Degradation by Commensal Microbes Shields Pathogens

Area of Science:

• Microbiology
• Genetics
• Public Health

Background:

• Gut microbiota harbors antibiotic resistance genes (ARGs), including beta-lactamase (BLA), which degrade antibiotics like ampicillin.
• Widespread antibiotic use has increased ARG prevalence in commensal bacteria.
• ARGs can protect sensitive bacteria from antibiotics via 'leaky protection' in coinfections.

Purpose of the Study:

• To investigate if commensal bacteria expressing ARGs can shield antibiotic-sensitive pathogens in the gut lumen.
• To determine if ARGs in commensals can destroy antibiotics and protect pathogens from treatment.

Main Methods:

• Germfree or wild-type mice were colonized with a commensal Escherichia coli strain producing functional or defective BLA.
• Mice were infected with Listeria monocytogenes or Clostridioides difficile.
• Mice were treated with oral ampicillin to assess pathogen clearance and dissemination.

Main Results:

• Commensal E. coli producing functional BLA significantly reduced pathogen clearance during ampicillin treatment.
• Pathogen dissemination was enhanced in mice with BLA-producing commensals.
• Pathogen resistance was due to antibiotic degradation by BLA, not horizontal gene transfer.

Conclusions:

• Commensal bacteria expressing ARGs can shield pathogens from antibiotic effects in the intestinal lumen.
• This mechanism, mediated by antibiotic degradation, represents a novel challenge in combating infections.