CTX-M-127 with I176F mutations found in bacteria isolates from Bangladeshi circulating banknotes

Area of Science:

• Microbiology
• Molecular Biology
• Drug Resistance

Background:

• Extended-spectrum beta-lactamase (ESBL)-producing organisms are significant causes of challenging infections.
• The CTX-M family of enzymes is a rapidly growing, globally distributed group found in Enterobacteriaceae.
• Banknotes are a potential vector for transmitting multidrug resistance due to frequent circulation.

Purpose of the Study:

• To screen for ESBL-carrying bacteria on banknotes in Bangladesh.
• To identify and characterize CTX-M mutations present on these banknotes.
• To investigate the potential impact of these mutations on antibiotic resistance, specifically to mecillinam.

Main Methods:

• Screening of ESBL-carrying bacteria from banknotes.
• Gene sequencing of CTX-M genes.
• Homology modeling of CTX-M variants using Swiss model.
• Molecular docking of mecillinam with wild-type and mutated CTX-M models using Autodock 4.2.
• Visual inspection of molecular interactions using PyMOL.

Main Results:

• Partially sequenced blaCTX-M genes showed relation to blaCTX-M-10 and blaCTX-M-15.
• Identified single-nucleotide substitution mutations: G613T (silent), A626T (I176F), and A503G (N135D).
• Homology modeling confirmed high similarity to the template; mutated residues (Asp135, Phe176) maintained similar orientations.
• Molecular docking predicted binding of mecillinam to Lys237, Ser240, and Asp135 residues, with lowest binding energy at Asp135.

Conclusions:

• The identified CTX-M mutations on Bangladesh banknotes are associated with blaCTX-M-15 and blaCTX-M-10.
• The N135D and I176F mutations may influence mecillinam binding.
• These findings support the hypothesis that CTX-M mutations contribute to mecillinam resistance, potentially linked to CTX-M-15 to CTX-M-127 conversion.