High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai Metropolitan Region

• DOI: 10.1186/s13073-022-01076-0
• Publication Date: 2022-08-21T23:02:53Z
• Authors: Viola Dreyer; Ayan Mandal; Prachi Dev; Matthias Merker; Ivan Barilar; Christian Utpatel; Kayzad Nilgiriwala; Camilla Rodrigues; Derrick W. Crook; ; Derrick W. Crook; Timothy E. A. Peto; A. Sarah Walker; Sarah J. Hoosdally; Ana L. Gibertoni ...; Joshua Carter; Sarah Earle; Samaneh Kouchaki; Yang Yang; Timothy M. Walker; Philip W. Fowler; Daniel Wilson; David A. Clifton; Zamin Iqbal; Martin Hunt; Jeff Knaggs; Daniela M. Cirillo; Emanuele Borroni; Simone Battaglia; Arash Ghodousi; Andrea Spitaleri; Andrea Cabibbe; Sabira Tahseen; Kayzad Nilgiriwala; Sanchi Shah; Camilla Rodrigues; Priti Kambli; Utkarsha Surve; Rukhsar Khot; Stefan Niemann; Thomas Kohl; Matthias Merker; Harald Hoffmann; Katharina Todt; Sara Plesnik; Nazir Ismail; Shaheed Vally Omar; Lavania Joseph Du...; Nana Okozi; Shen Yuan Yao; Guy Thwaites; Thuong Nguyen Thu...; Nhung Hoang Ngoc; Vijay Srinivasan; David Moore; Jorge Coronel; Walter Solano; George F. Gao; Guangxue He; Yanlin Zhao; Aijing Ma; Chunfa Liu; Baoli Zhu; Ian Laurenson; Pauline Claxton; Robert J. Wilkinson; Anastasia Koch; Ajit Lalvani; James Posey; Jennifer Gardy; Jim Werngren; Nicholas Paton; Ruwen Jou; Mei-Hua Wu; Yu-Xin Xiao; Lucilaine Ferrazoli; Rosangela Siqueir...; James Millard; Rob Warren; Annelies Van Rie; Simon Grandjean L...; Marie-Sylvianne R...; Niaina Rakotosami...; Camus Nimmo; Kimberlee Musser; Vincent Escuyer; Ted Cohen; Jean-Philippe Ras...; Thierry Wirth; Nerges Mistry; Stefan Niemann
• Keywords: Human genetics

Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains are a serious health problem in India, also contributing to one-fourth of the global MDR (TB) burden. About 36% MTBC reported fluoroquinolone (FQ) resistant leading high pre-extensively drug-resistant (pre-XDR) and XDR-TB (further resistance against bedaquiline and/or linezolid) rates. Still, factors driving MDR/pre-XDR epidemic India not well defined. In retrospective study, we analyzed 1852 consecutive obtained from patients tertiary care hospital laboratory Mumbai by whole genome sequencing (WGS). Univariate multivariate statistics was used investigate associated with pre-XDR. Core multi locus sequence typing, time scaled haplotypic density (THD) method homoplasy analysis were analyze epidemiological success, positive selection different strain groups, respectively. total, 1016 MDR, out which 703 (69.2%) pre-XDR 45 (4.4%) XDR. Cluster rates among (57.8%) pre-XDR/XDR (79%) three dominant L2 (Beijing) clusters (Cl 1-3) representing half 40% cases. pre-XDR/XDR-TB (P < 0.001) and, particularly Cl 1-3 strains, had first-line FQ (81.6-90.6%). Epidemic success using THD showed that outperformed L1, L3, L4 short- long-term scales. More importantly, + higher indices than their not-MDR counterparts. Overall, compensatory mutation highest detected genes drug tolerance (prpB ppsA) virulence (Rv2828c). Compensatory mutations threefold increase indices, suggesting improved transmissibility. Our data indicate drastic resistance, as emerging endangers newly endorsed MDR-TB treatment regimens. Rapid changes control strategies required contain transmission highly successful Metropolitan region but presumably India-wide.