First genetic characterization of multi-drug resistant Mycobacterium tuberculosis isolates from Algeria

Abstract Objectives to characterize the genotypes of multidrug resistant (MDR) Mycobacterium tuberculosis (MTB) isolated in Algeria, where a low MDR-MTB incidence rate is observed. Methods 10 MDR isolates and one resistant to isoniazid were investigated by PCR-Sanger sequencing for 10 loci involved in resistance. Amplicon-based NGS of 15 loci was additionally performed on isolates harboring novel mutations. Results Sanger and amplicon-NGS sequencing provided the same results concordant with GenoType kits. Mutations known to be associated with resistance were described for most isolates: rpoB S531 L in 7/10 rifampicin-R MTB isolates, katG S315 T in 9/11 isoniazid-R and promoter inhA c-15 t in 3/11 of them, embB M306 V or M306I in 2/2 ethambutol-R, rpsL K43R in 4/8 or rrs a514c associated with gidB L16R in streptomycin-R, gyrA A90 V in the ofloxacin-R pre-XDR isolate. New and rare mutations were also described in rpoB (deletion 512-513-514), katG (S315R, M126I/ R496 L), gidB (V124 G, E92A, V139A, G37 V) and gyrA (P8A). MIRU-VNTR profiles were similar for 3 isolates (lineage Cameroon) indicating a possible clonal diffusion with patients not epidemiologically related. Conclusions Resistant MTB isolates in Algeria harbor resistance genotypes similar as in other countries but some rare patterns may result from selection and transmission processes inherent to the country.