Abstract
BACKGROUND: Multidrug-resistant (MDR) Escherichia coli (E.coli) is a growing public health concern, largely driven by the overexpression of efflux pumps such as AcrAB-tolC. These efflux systems contribute to resistance against multiple antibiotic classes, including fluoroquinolones, β-lactams, and aminoglycosides. Despite the well-documented role of efflux pumps in resistance, inconsistencies in reported expression levels and regulatory mechanisms complicate the development of targeted therapies. This systematic review and meta-analysis aim to consolidate available evidence on acrAB-tolC expression patterns and evaluate the impact of efflux pump inhibitors (EPIs) on antibiotic susceptibility. METHODS: A systematic search was conducted in PubMed, Scopus, Google Scholar, and EBSCO to identify relevant studies examining acrAB expression in E.coli under antibiotic exposure conditions. Inclusion criteria encompassed experimental studies utilizing qPCR, RNA-seq, or microarray techniques to quantify acrAB expression, as well as research assessing the efficacy of EPIs in restoring antibiotic susceptibility. Data synthesis was performed using a random-effects meta-analysis model, and heterogeneity was assessed using the I² statistic. RESULTS: A total of 10 studies were included in the final meta-analysis. Pooled analysis demonstrated a significant increase in acrAB expression (SMD: 3.5, 95% CI: 2.1-4.9) in MDR E.coli isolates compared to susceptible strains. Efflux inhibition resulted in a ≥ 4-fold reduction in minimum inhibitory concentrations (MICs) for fluoroquinolones and β-lactams across multiple studies. Risk ratio analysis showed that EPIs significantly restored antibiotic susceptibility (RR: 4.2, 95% CI: 3.0-5.8). However, substantial heterogeneity was noted among studies due to methodological variations. CONCLUSION: These findings confirm that acrAB-tolC overexpression is a major contributor to antibiotic resistance in E.coli and that efflux inhibition is a viable strategy for restoring antibiotic susceptibility. However, clinical translation remains a challenge due to toxicity concerns and pharmacokinetic limitations of current EPIs. Future research should focus on developing safer efflux inhibitors, optimizing combination therapies, and standardizing efflux pump expression assays to facilitate their integration into antimicrobial treatment strategies.