OR03
Diversity of Mycobacterium tuberculosis complex Lineage 1 - phylogeography, sub-lineages and their associated phenolic glycolipid patterns
N Gisch(1) C Utpatel(2) L M Gronbach(1) T A Kohl(2) U Schombel(1) S Malm(2) K M Dobos(3) D C Hesser(3) R Diel(4) U Götsch(5) S Gerdes(6) Y A Shuaib(7,8) N E Ntinginya(9) C Khosa(10) S Viegas(10) G Kerubo(11) S Ali(12) S A Al-Hajoj(13) P W Ndung’u(14) A Rachow(15,16) M Hoelscher(15,16) F P Maurer(17,18) D Schwudke(1,19,20) S Niemann(2,19) N Reiling(19,21) S Homolka(2)
1:Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; 2:Molecular and Experimental Mycobacteriology, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; 3:Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, United States; 4:Lung Clinic Grosshansdorf, Airway Disease Center North (ARCN), German Center for Lung Research (DZL), Großhansdorf, Germany; 5:Municipal Health Authority Frankfurt am Main, Frankfurt am Main, Germany; 6:Municipal Health Authority Hannover, Hanover, Germany; 7:College of Veterinary Medicine, Sudan University of Science and Technology, Khartoum, Sudan; 8:WHO-Supranational Reference Laboratory of Tuberculosis, Institute of Microbiology and Laboratory Medicine (IML Red), Gauting, Germany; 9:National Institute for Medical Research Tanzania – Mbeya Medical Research Center, Mbeya, Tanzania; 10:Instituto Nacional de Saúde (INS), Marracuene, Mozambique; 11:Department of Medical Microbiology and Parasitology, School of Medicine, Kenyatta University, Nairobi, Kenya; 12:Department of Microbiology, Immunology, and Parasitology, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia; 13:Mycobacteriology Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 14:Institute of Tropical Medicine and Infectious Diseases (ITROMID), Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya; 15:Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany; 16:German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany; 17:National and WHO Supranational Reference Centre for Mycobacteria, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; 18:Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf,Hamburg, Germany; 19:German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel,Germany; 20:Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany; 21:Microbial Interface Biology, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany
“Ancestral” Mycobacterium tuberculosis complex (MTBC) strains of Lineage 1 (L1, East African Indian) are one of the major infectious agents causing tuberculosis (TB) in countries around the Indian Ocean. Phthiocerol dimycocerosates (PDIM) and phenolic glycolipids (PGL) have been discussed as lipid virulence factors of MTBC strains associated with mycobacterial host evasion and modulation of the host immune response. However, these factors are insufficiently characterized for L1 strains. Here, we used whole genome sequencing (WGS) of 312 L1 strains from 43 countries for a characterization of the global L1 phylogeography and population structure. Presence of PGL was analyzed by NMR-based lipid profiling and correlated to newly defined sub-lineages. Our results reveal a South-Asian origin of the MTBC L1 with several introduction events to countries around the Indian Ocean and beyond and the presence of eight major L1 sub-lineages, whose members have specific mutation signatures in PGL biosynthesis genes, e.g., pks15/1 or glycosyltransferases Rv2962c and/or Rv2958c. Sub-lineage specific PGL patterns were identified and strains with a completely abolished phenolphthiocerol dimycoserosate biosynthesis showed in average a more prominent growth in human macrophages.
In conclusion, our results show a diverse population structure of L1 strains that is associated with the presence of specific PGL types. This includes the occurrence of mycoside B in one sub-lineage, representing the first description of a PGL in an M. tuberculosis lineage other than L2. Such differences may be important for the evolution of L1 strains, e.g., allowing adaption to different human populations.