Toxin-antitoxin systems shows variability among Mycobacterium tuberculosis lineages

Area of Science:

• Microbiology
• Genomics
• Molecular Biology

Background:

• Toxin-antitoxin (TA) systems are crucial genetic elements in microorganisms, particularly in Mycobacterium tuberculosis (MTB), influencing cell persistence and stress responses.
• These systems are widely distributed across different MTB lineages.

Purpose of the Study:

• To investigate the distribution and sequence variability of TA systems across seven distinct MTB lineages.
• To identify potential genetic markers for MTB genotyping.

Main Methods:

• Protein prediction using Prodigal on 73 MTB genomes.
• Construction of profile hidden Markov models (PHMMs) for 225 reference TA proteins using HMMER.
• Homology searches, operon identification, orthologous gene clustering, and multiple sequence alignments for mutation scanning.

Main Results:

• All identified TA proteins belonged to types II and IV.
• 45 TA proteins were found to be completely conserved across lineages.
• Six uncharacterized antitoxins with homology to known types were identified.
• Lineage-specific mutations, including frameshift mutations in 46 TA proteins, were detected, indicating genetic variability.

Conclusions:

• Significant sequence variability exists within TA systems across different MTB lineages.
• Identified mutations provide potential targets for developing novel genotyping strategies for Mycobacterium tuberculosis.