Whole Genome Sequencing of Clinical Samples Reveals Extensively Drug Resistant Tuberculosis (XDR TB) Strains From The Beijing Lineage in Nigeria, West Africa.

Abstract

Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex (MTBC) from clinical samples in Nigeria. Our findings further reveal the presence of resistance genes to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.

50S subunit recognition and modification by the Mycobacterium tuberculosis ribosomal RNA methyltransferase TlyA

“…Clinical resistance to capreomycin can arise through 16S rRNA mutation (27,28) or via amino acid substitutions in TlyA that eliminate its activity and thus incorporation of the rRNA methylation required for optimal capreomycin activity (28)(29)(30)(31). To directly test whether these TlyA mutations result in enzymes lacking activity due to structural disruption of key interactions with the ribosome subunits, we created additional TlyA variants corresponding to three Mtb mutations associated with capreomycin resistance, R14W, A67E and N236K (28)(29)(30)(31).…”

Liposomes techniques of aerosolization for the treatment of obstructive, restrictive and infectious pulmonary diseases: a review

“…A tuberculose (TB) é uma doença crônica, altamente infecciosa, que mais mata no mundo, de acordo com dados da Organização Mundial de Saúde (2018). Em 2019, foi estimado que 10 milhões de pessoas estavam contaminadas com TB, e, dentre estas, em média 1.2 milhões de pessoas vieram a óbito (Olawoye, et al, 2021). Atualmente, ela é considerada uma das maiores ameaças à saúde pública global representando uma emergência sanitária desde 1993 por sua alta taxa de mortalidade, morbidade e alta incidência na população nas últimas décadas (Furin, et al, 2019;WHO, 2020).…”