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

Objectives: to characterize the resistance (R) genotypes for multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) isolates from Algeria, where a low MDR-Mtb incidence rate is observed.Methods: Eleven isolates (10 MDR and one resistant to isoniazid [INH)) were investigated by PCR-Sanger sequencing for 10 loci involved in resistance. Amplicon-based NGS was performed on complementary loci for two isolates. Results: Sanger and amplicon-NGS sequencing provided the same results concordant with routine GenoType kits. Mutations known to be associated with resistance were described for most of the isolates: rpoB S531L in 7/10 Mtb in rifampicin-R isolates, katG S315T in 9/11 and promoter inhA c-15t in 3/11 in INH-R, embB M306V or I in 2/2 ethambutol-R, rpsL K43R in 4/8 or rrs a514c associated with gidB L16R in Streptomycin-R, gyrA A90V in the fluoroquinolone-R pre-XDR isolate. New mutations or polymorphisms were described in rpoB (deletion 512-513-514), katG (R496L), embB (Y319S, D328Y), gidB (V124G, E92A, V139A, G37V, n115 deletion). MIRU-VNTR profiles were similar for 3 isolates (lineage Cameroon) indicating a possible clonal diffusion with patients not epidemiologically related. Conclusion: Resistant Mtb isolates in Algeria harbor similar resistance genotypes as other countries but some rare patterns result from selection and transmission processes inherent to the country.