Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant <i>Mycobacterium tuberculosis</i> in Zambia

• Main Authors: Precious Bwalya (Author), Tomoyuki Yamaguchi (Author), Eddie Samuneti Solo (Author), Joseph Yamweka Chizimu (Author), Grace Mbulo (Author), Chie Nakajima (Author), Yasuhiko Suzuki (Author)
• Format: Book
• Published: MDPI AG, 2021-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics10101169; 2079-6382
• Keywords: <i>Mycobacterium tuberculosis</i>; streptomycin; multidrug-resistant tuberculosis (MDR-TB); spoligotype; Zambia; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 10, Iss 10, p 1169 (2021)

Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in <i>rpsL</i>, <i>rrs,</i> and <i>gidB</i> accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in <i>rpsL</i> was strongly associated with the CAS1_Kili genotype (<i>p</i> < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.