Antibiotics (Dec 2021)

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant <i>Mycobacterium tuberculosis</i> CAS1-Kili Strains in Lusaka, Zambia

  • Joseph Yamweka Chizimu,
  • Eddie Samuneti Solo,
  • Precious Bwalya,
  • Wimonrat Tanomsridachchai,
  • Herman Chambaro,
  • Misheck Shawa,
  • Thoko Flav Kapalamula,
  • Patrick Lungu,
  • Yukari Fukushima,
  • Victor Mukonka,
  • Jeewan Thapa,
  • Chie Nakajima,
  • Yasuhiko Suzuki

DOI
https://doi.org/10.3390/antibiotics11010029
Journal volume & issue
Vol. 11, no. 1
p. 29

Abstract

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Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.

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