Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host

• DOI: 10.3389/fmicb.2023.1244319
• Publication Date: 2023-10-09T11:21:46Z
• Authors: Paula Josefina Gó...; Anna D. Grabowska; Leopold D. Tientcheu; Anthony G. Tsolaki; Martin L. Hibberd; Susana Campino; Jody E. Phelan; Taane G. Clark
• Keywords: 570; pe/ppe family of genes; 0303 health sciences; 03 medical and health sciences; genomics; MTBC; 610; Mycobacerium tuberculosis; Microbiology; QR1-502; 3. Good health; diversity

Introduction Around 10% of the coding potential Mycobacterium tuberculosis is constituted by two poorly understood gene families, pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature high GC content have hindered sequence analysis, leading exclusion from whole-genome studies. Understanding genetic diversity pe/ppe families essential facilitate their translation into tools for prevention treatment. Methods To investigate 169 / genes, we performed a analysis across 73 long-read assemblies representing seven different lineages M. bovis BCG. Individual alignments were extracted conservation studied. Results The genes classified three groups based on level protein relative H37Rv, finding that >50% conserved, with indels pe_pgrs ppe_mptr sub-families being major drivers structural variation. Gene rearrangements, such as duplications fusions, observed between genes. Inter-lineage revealed lineage-specific SNPs indels. Discussion conservation, together findings, suggest phylogenetic informativeness. However, variants rearrangements differing reference also identified, implications pathogenicity. Overall, improving our knowledge these complex may insights pathogenicity inform development much-needed control.