# Efflux-Mediated Macrolide Resistance in Clinical Streptococcus Isolates: A Comparative Molecular Study

## TL;DR

This study investigates macrolide resistance in Streptococcus isolates from UAE hospitals, finding mef(A/E) as a key resistance gene with regional differences.

## Contribution

The first molecular characterization of efflux-mediated macrolide resistance in UAE Streptococcus isolates.

## Key findings

- Mef(A/E) gene was detected in 31% of isolates and strongly predicted macrolide resistance.
- UAE isolates showed 31% mef(A/E) prevalence, significantly lower than 87% in India and 0% in Saudi Arabia.
- No isolates harbored tet(K), and msr(D) was rare at 3% prevalence.

## Abstract

Background: Efflux-mediated macrolide resistance represents an emerging threat in Streptococcus infections globally. However, molecular epidemiological data from the Gulf region, particularly the United Arab Emirates (UAE), remain limited. This study addresses this knowledge gap by investigating efflux pump resistance mechanisms in clinical Streptococcus isolates. Methods: A cross-sectional study analyzed 100 clinical isolates (99 Streptococcus and 1 Enterococcus) from Thumbay Hospital, Ajman, UAE (October–December 2024). Antimicrobial susceptibility testing for minimum inhibitory concentration (MIC) determination was performed using the DxM 1096 MicroScan WalkAway system (Beckman Coulter Inc., Brea, CA, USA; LabProv4.42). PCR detected mef(A/E), msr(D), and tet(K) resistance genes with sequencing confirmation. Comparative genomic analysis was performed using a total of 30 publicly available Streptococcus genomes: 15 from India and 15 from Saudi Arabia. Statistical analysis employed chi-square tests, Fisher’s exact tests, and multivariate logistic regression with Bonferroni correction (α = 0.05). Results: Among the isolates, erythromycin resistance occurred in 39 isolates (39%, 95% CI: 29.4–49.2%) and clindamycin resistance in 31 isolates (31%, 95% CI: 22.1–40.9%). The mef(A/E) gene was detected in 31 isolates (31%, 95% CI: 22.1–40.9%), and msr(D) in 3 isolates (3%, 95% CI: 0.6–8.5%), with co-occurrence in 3 isolates (3%). No isolates harbored tet(K). Multivariate analysis identified mef(A/E) as the strongest predictor of macrolide resistance (OR = 18.7, 95% CI: 7.9–44.2, p < 0.001). Regional comparison revealed significant differences: mef(A/E) prevalence was 31% (UAE), 87% (India), and 0% (Saudi Arabia) (p < 0.001). Conclusions: This study provides the first molecular characterization of efflux-mediated macrolide resistance in UAE Streptococcus isolates. The predominance of mef(A/E)-mediated resistance with confirmed efflux activity highlights the clinical significance of active surveillance and targeted antimicrobial stewardship in the region.