Computer Program for Detection and Analyzing the Porin-Mediated Antibiotic Resistance of Bacteria

Area of Science:

• Microbiology
• Genetics
• Bioinformatics

Background:

• Antibiotic resistance in gram-negative bacteria is a growing global health threat.
• Porin-mediated resistance significantly contributes to antibiotic resistance in Pseudomonas aeruginosa.
• Understanding the genetic basis of this resistance is crucial for developing effective treatments.

Purpose of the Study:

• To develop a novel software tool for identifying gene mutations conferring porin-mediated antibiotic resistance.
• To validate the software's functionality by detecting carbapenem resistance mechanisms in clinical Pseudomonas aeruginosa isolates.

Main Methods:

• Algorithm development based on sequence homology between reference and studied genes.
• Genomic analysis including nucleotide and amino acid sequence comparisons.
• Utilized reference genes from susceptible P. aeruginosa ATCC 27853 and clinical isolates from PATRIC database and own collection.
• Phenotypic characterization according to CLSI standards and carbapenemase gene detection using ResFinder 4.1.

Main Results:

• The developed software identified various mutations in porin genes (OprD, OpdD, OpdP) of P. aeruginosa.
• Single amino acid substitutions were common in OpdD and OpdP.
• Carbapenem-resistant strains showed significant modifications in the OprD gene, including insertions/deletions leading to premature termination.
• Alternative resistance mechanisms were suggested in meropenem-resistant isolates lacking OprD mutations.

Conclusions:

• The software is an effective tool for elucidating molecular genetic mechanisms of chromosomal antibiotic resistance.
• The study highlighted differences in mutation prevalence across oprD, opdD, and opdP genes associated with carbapenem resistance.