Molecule Information

General Information of the Molecule (ID: Mol00756)

• Name: 30S ribosomal protein S12 (RPSL) ,Mycobacterium tuberculosis
• Synonyms: rps12; Rv0682; MTV040.10
• Molecule Type: Protein
• Gene Name: rpsL
• Gene ID: 45424644
• Sequence:
  MPTIQQLVRKGRRDKISKVKTAALKGSPQRRGVCTRVYTTTPKKPNSALRKVARVKLTSQ
  VEVTAYIPGEGHNLQEHSMVLVRGGRVKDLPGVRYKIIRGSLDTQGVKNRKQARSRYGAK
  KEKG
• 3D-structure: PDB ID: 7SFR; Classification: Ribosome/antibiotic; Method: Electron microscopy; Resolution: 2.60 Å
• Function: Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit (By similarity).
• Uniprot ID: RS12_MYCTU

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Corynebacteriales
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Streptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: HIV-infected patients with tuberculosis [ICD-11: 1C60.0] [1], [2], [3]

• Resistant Disease: HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
• Resistant Drug: Streptomycin
• Molecule Alteration: Mutantion; p.K43R+p.K88Q+p.K88R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis strain; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Mycobacterium tuberculosis is associated either with missense mutations in the rpsL gene, which encodes ribosomal protein S12, or with base substitutions at position 904 in the 16S rRNA.Streptomycin resistant isolates harbored mutations in rpsL (codons k43R, k88Q, k88R) and rrs (nucleotide A514C).

Disease Class: bifidobacterium adolescentis infection [ICD-11: XN33F] [4]

• Resistant Disease: bifidobacterium adolescentis infection [ICD-11: XN33F]
• Resistant Drug: Streptomycin
• Molecule Alteration: Missense mutation; A98G+K103N+P225H
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Bifidobacterial strains; 1763
• Experiment for Molecule Alteration: PCR; Catalase foam assay; Catalase gel assay
• Experiment for Drug Resistance: Growth curve assay; Spot assay; Anti-tubercular drug uptake and surface assay; Adaptability assay; FE-SEM assay; MIC assay; Particle size assay
• Mechanism Description: The current study aims to understand the resistance of Bifidobacterium adolescentis to different anti-tubercular drugs (first-line oral tuberculosis drugs). The bacteria were grown with anti-tubercular drugs such as isoniazid, pyrazinamide, and streptomycin to better understand the resistance phenomena. It was found that even at tenfold higher concentrations, growth rates remained unchanged. In addition, a small number of bacteria were found to aggregate strongly, a property that protects against the toxicity of the drug. Further FE-SEM (Field Emission Scanning Electron Microscopy) analysis revealed that some bacteria became excessively long, elongated, and protruded on the surface. Size scattering analysis confirmed the presence of bifidobacteria in the size range of 1.0-100 um. After whole genome sequence analysis, certain mutations were found in the relevant gene. In vitro, foam formation and growth in the presence of H2O2 and HPLC (High Performance Liquid Chromatography) studies provide additional evidence for the presence of catalase. According to RAST (Rapid Annotation Using Subsystems Technology) annotation and CARD (Comprehensive Antibiotic Resistance Database analysis), there were not many components in the genome that were resistant to antibiotics. Whole genome sequence (WGS) analysis does not show the presence of bacteriocins and antibiotic resistance genes, but few hypothetical proteins were observed. 3D structure and docking studies suggest their interaction with specific ligands.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [5]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Streptomycin
• Molecule Alteration: Mutation; Q24K+L28M+R30E+A92K
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

References

• Ref 1: Molecular characterisation of streptomycin-resistant Mycobacterium tuberculosis strains isolated in Poland. Int J Tuberc Lung Dis. 2004 Aug;8(8):1032-5.
• Ref 2: Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol Microbiol. 2007 Feb;63(4):1096-106. doi: 10.1111/j.1365-2958.2006.05585.x.
• Ref 3: Drug resistance-conferring mutations in Mycobacterium tuberculosis from Madang, Papua New Guinea. BMC Microbiol. 2012 Sep 4;12:191. doi: 10.1186/1471-2180-12-191.
• Ref 4: Bifidobacterium adolescentis is resistant to pyrazinamide, isoniazid, and streptomycin. Sci Rep. 2024 Nov 28;14(1):29562.
• Ref 5: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.