Insertion and deletion evolution reflects antibiotics selection pressure in a Mycobacterium tuberculosis outbreak

Area of Science:

• Genomics
• Evolutionary Biology
• Microbiology

Background:

• Genetic variants drive genome evolution and adaptation.
• Tuberculosis treatment selects for antibiotic resistance in Mycobacterium tuberculosis (MTB).
• The role of insertions and deletions (indels) in MTB evolution is understudied compared to point substitutions.

Purpose of the Study:

• To investigate the frequency and impact of high-quality indels in a multi-drug resistant MTB outbreak.
• To understand the evolutionary dynamics and contribution of indels to antibiotic resistance in MTB.

Main Methods:

• Analysis of indels and substitutions in MTB strains from a multi-drug resistant outbreak.
• Assessment of indel inheritance and evolutionary rate using a molecular clock.
• Examination of co-occurrence of indels and substitutions in relevant genes.

Main Results:

• Indels are significantly enriched in genes associated with antibiotic resistance.
• Indels are inherited within the MTB outbreak and evolve at a slower rate than substitutions.
• Co-occurrence of indels and substitutions observed in genes related to iron storage and second-line antibiotic resistance.

Conclusions:

• Indels play a significant role in the evolution of antibiotic resistance in Mycobacterium tuberculosis.
• Epistatic interactions between indels and substitutions influence MTB adaptation and compensatory evolution.
• Understanding indel dynamics is crucial for comprehending MTB genome evolution under treatment pressure.