Drug-resistance profiling and transmission dynamics of multidrug-resistant Mycobacterium tuberculosis in Saudi Arabia revealed by whole genome sequencing.

Abstract:

Background:In Saudi Arabia, cross-border transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains might be particularly fostered by high immigration rates. Herein, we aimed to elucidate the transmission dynamics of MDR-MTBC strains and reveal a detailed prediction of all resistance-conferring mutations for the first- and second-line drugs. Methods:We investigated all MDR-MTBC strains collected between 2015 and 2017 from provincial mycobacteria referral laboratories and compared demographic and clinical parameters to a cohort of non-MDR-TB patients using a whole genome sequencing approach. Clusters were defined based on a maximum strain-to-strain genetic distance of five single-nucleotide polymorphisms (SNPs) as surrogate marker for recent transmission, and then investigated molecular drug-resistance markers (37 genes). Results:Forty-eight (67.6%) MDR-MTBC strains were grouped in 14 different clusters, ranging in size from two to six strains; 22.5% (16/71) of all MDR-MTBC isolates were predicted to be fully resistant to all five first-line drugs, and five strains (7.0%) exhibited fluoroquinolone resistance. Moreover, we revealed the presence of 12 compensatory mutations as well as 26 non-synonymous SNPs in the rpoC gene and non-hotspot region in rpoB, respectively. Conclusion:Optimized TB molecular surveillance, diagnosis, and patient management are urgently needed to contain MDR-MTBC transmission and prevent the development of additional drug resistance.

journal_name

Infect Drug Resist

authors

Al-Ghafli H,Kohl TA,Merker M,Varghese B,Halees A,Niemann S,Al-Hajoj S

doi

10.2147/IDR.S181124

subject

Has Abstract

pub_date

2018-11-12 00:00:00

pages

2219-2229

issn

1178-6973

pii

idr-11-2219

journal_volume

11

pub_type

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