MOLECULAR CHARACTERIZATION OF THE pmrCAB GENES ASSOCIATED WITH COLISTIN RESISTANCE IN CLINICAL ISOLATES OF Acinetobacter baumannii

Abstract

Acinetobacter baumnnii (A. baumannii) represents a significant threat to public health, severely limiting the effectiveness of existing antimicrobial treatments. Currently, colistin is used as a last-resort treatment for infections caused by multidrug-resistant and extensively drug-resistant A. baumannii, due to the increasing rates of resistance to both first- and second-line antibiotics. Regrettably, reports of colistin resistance (CoR) in A. baumannii clinical isolates have been growing frequently. This study aims to investigate the incidence of mutations in the pmrCAB operon, characterize the alterations found within isolates, and examine the diversity and complexity of colistin resistance in A. baumannii. In this study, 46 unique isolates of A. baumannii from hospitalized patients are identified using the Phoenix BD Diagnostic System, which serves for bacterial identification and antimicrobial susceptibility profiling. Additionally, these isolates are confirmed through PCR analysis of the bla_OXA-51-like gene. Based on CLSI 2024 guidelines, a significant proportion of isolates were multidrug-resistant 25 (54.4%), extensively drug-resistant 18 (39.1%), or pandrug-resistant 6 (6.5%). High resistance rates were observed for meropenem (93.4%) and imipenem (91.3%). Colistin resistance was detected in 6.5% (3/46) of isolates, all of which were positive for pmrCAB genes. Additionally, this study identified point mutations in the pmrC gene, resulting in a specific amino acid alteration (Val42→Ile) in the EptA protein, located within the transmembrane region. In conclusion, this study highlights the high prevalence of MDR-XDR A. baumannii clinical isolates, emphasizing the urgent requirement for effective control strategies. Furthermore, pmrC point mutations and distinct amino acid substitutions may contribute to low-to-moderate modification of lipid A within the lipopolysaccharide, which may contribute to colistin resistance. However, direct impact on bacterial virulence requires further investigation.