Unexpected Genomic and Phenotypic Diversity of Mycobacterium africanum Lineage 5 Affects Drug Resistance, Protein Secretion, and Immunogenicity

Genome Biology and Evolution
Louis S AtesRoland Brosch

Abstract

Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed a previously underappreciated diversity within L5, which consists of distinct sublineages. L5 strains caused relatively high levels of extrapulmonary tuberculosis and included multi- and extensively drug-resistant isolates, especially in the newly defined sublineage L5.2. The specific L5 sublineages also exhibit distinct phenotypic characteristics related to in vitro growth, protein secretion and in vivo immunogenicity. In particular, we identified a PE_PGRS and PPE-MPTR secretion defect specific for sublineage L5.2, which was independent of PPE38. Furthermore, L5 isolates were able to efficiently secrete and induce immune responses against ESX-1 s...Continue Reading

References

Jun 1, 1980·Tubercle·M F Thorel
Jul 1, 1997·Antimicrobial Agents and Chemotherapy·W H HaasH J Bremer
May 15, 1999·Journal of Clinical Microbiology·R FrothinghamD L Williams
Dec 20, 2000·Bioinformatics·K RutherfordB Barrell
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·R BroschS T Cole
Jun 29, 2002·The Journal of Infectious Diseases·Serge MostowyMarcel A Behr
Jun 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thierry GarnierR Glyn Hewinson
Mar 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anthony G TsolakiPeter M Small
Aug 7, 2004·Journal of Clinical Microbiology·Serge MostowyMarcel Behr
Nov 6, 2004·Journal of Clinical Microbiology·Karine BrudeyChristophe Sola
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laleh MajlessiClaude Leclerc
Jun 25, 2005·Bioinformatics·Tim J CarverJulian Parkhill
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sebastien GagneuxPeter M Small
Nov 2, 2006·Molecular Microbiology·Abdallah M AbdallahWilbert Bitter
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jul 16, 2009·Molecular Microbiology·Abdallah M AbdallahWilbert Bitter
Sep 23, 2009·BMC Evolutionary Biology·Christopher R E McEvoyNicolaas C Gey van Pittius
Mar 31, 2010·BMC Infectious Diseases·Sidra E Gonçalves VasconcellosJohn L Ho
May 25, 2010·Nature Genetics·Iñaki ComasSebastien Gagneux
Oct 12, 2010·PLoS Neglected Tropical Diseases·Bouke C de JongSebastien Gagneux
Oct 29, 2010·Tuberculosis·Jocelyne M LewStewart T Cole
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Feb 11, 2011·Nucleic Acids Research·Thomas D OttoMatthew Berriman
Feb 4, 2012·The Journal of Infectious Diseases·Tyler D BoldBouke C de Jong
Apr 18, 2012·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Anton BankevichPavel A Pevzner
Aug 29, 2012·Molecular Microbiology·Edith N G HoubenWilbert Bitter

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Citations

Jun 21, 2019·Microorganisms·Rachael A FiewegerBrian C VanderVen
Mar 6, 2019·Journal of Bacteriology·Rachel E BossermanPatricia A Champion
Sep 26, 2019·Frontiers in Microbiology·Baltazar CáMargarida Saraiva
Sep 14, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Marcelo Fouad RabahiPhilip Noel Suffys
Dec 14, 2018·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Jan MadackiRoland Brosch
May 28, 2021·Nature Reviews. Microbiology·Angel Rivera-CalzadaSebastian Geibel
Jul 13, 2019·Microbiology Spectrum·Farzam Vaziri, Roland Brosch
Oct 5, 2021·Lipids in Health and Disease·Daniel MekonnenAbraham Aseffa

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