Molecular Characterization of Colistin Resistance Acinetobacter baumannii Isolates and Identification of Mutations in pmrA and lpxA Genes from a Tertiary Care Hospital in South India
TL;DR
This is the first report on the molecular mechanisms of colistin resistance in South India using PCR and the first to report four novel mutations in the genes that may be responsible for resistance.
Abstract
Background/Objectives: Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen associated with significant morbidity and mortality. The emergence of strains resistant to multiple antibiotics has markedly reduced available treatment options. A. baumannii now demonstrates resistance to most first-line antibiotics, resulting in the extensive use of colistin, which in turn has led to the emergence of colistin-resistant strains. There are very limited studies from India on the mechanisms of colistin resistance. In this study, we focused on the molecular mechanisms leading to colistin resistance. Methods: A total of 225 clinical isolates of Acinetobacter baumannii were analyzed in this study. Antimicrobial susceptibility testing was done using the disk diffusion method for various classes of antimicrobial agents as per the Clinical Laboratory Standards Institute (CLSI M100 Ed 35,2025). Susceptibility to colistin was tested by the Microbroth dilution method. Colistin resistance mediated by the mcr gene and alterations in the pmrAB and lpxACD genes were investigated using conventional PCR followed by mutational analysis. Results: Among the 225 isolates, 4 isolates were found to be colistin resistant. All the resistant isolates had an MIC ≥ 16 mcg/mL. Mutations were found in lpxA and pmrB (c.391T > C, c.495T > C, c.516A > G, c.732A > G and c.966T > C). Mutations in pmrA, lpxC, and lpxD were not detected in this study. Mcr-1 gene was not detected in this study. Conclusions: Colistin is the last resort for the treatment of MDR strains, and the increase in resistance to colistin has become a huge concern among the medical community as it reduces the options available for treatment. This is the first report on the molecular mechanisms of colistin resistance in South India using PCR. The study is also the first to report four novel mutations in the genes that may be responsible for resistance. Early detection of resistance and swift control measures can help curb the morbidity and mortality rate among such A. baumannii strains.