Leveraging the human microbiota to target bacterial respiratory pathogens: new paths toward an expanded antimicrobial...

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Acute respiratory infections are a leading cause of death in children globally.
• Antibiotic resistance is a growing threat, with few new drugs in development.
• Microbial natural products are the primary source of current antibiotics.

Purpose of the Study:

• To identify novel microbial sources of antibacterial compounds.
• To investigate the potential of the respiratory microbiota as a source of biotherapeutics.
• To explore new strategies for combating antibiotic-resistant respiratory pathogens.

Main Methods:

• Screening of Rothia species for antimicrobial activity against Moraxella catarrhalis.
• In vitro and ex vivo assays to confirm growth inhibition.
• Analysis of secreted factors responsible for antimicrobial activity, including peptidoglycan endopeptidases.

Main Results:

• Rothia species demonstrated significant in vitro and ex vivo inhibition of Moraxella catarrhalis growth.
• A novel peptidoglycan endopeptidase secreted by Rothia was identified as a key factor in this activity.
• The identified enzyme targets the cell wall of Moraxella catarrhalis.

Conclusions:

• The human respiratory microbiota harbors potential biotherapeutic agents.
• Rothia species and their secreted enzymes represent a promising source for novel antibacterial drug discovery.
• These findings contribute to the urgent need for new treatments against antimicrobial resistance.