Photodynamic therapy with Rose Bengal against resistant Stenotrophomonas maltophilia: effects on SmeDEF efflux gene expression.

Abstract

Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic pathogen that has been implicated in causing infections such as pneumonia, bacteremia, and skin and soft-tissue infections, particularly in patients with compromised immune systems. The worldwide emergence of antibiotic-resistant bacteria continues to rise. Antimicrobial photodynamic therapy (aPDT) has been investigated as a promising treatment for localized infections in response to the ever-growing problem of antimicrobial resistance. This research was designed to investigate the antibiotic resistance profile of S. maltophilia, confirm the effectiveness of aPDT with Rose Bengal against resistant isolates, and compare the expression of the smeDEF efflux pump gene before and after aPDT. A total of 139 S. maltophilia isolates were collected during 2023 to 2024 in this cross-sectional study. The isolates were identified using routine microbiological and biochemical methods and confirmed by molecular polymerase chain reaction (PCR) targeting the 23 S rRNA gene. Antibiotic susceptibility was determined using both Kirby-Bauer disk diffusion and E-test methods, following Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines. aPDT was applied to S. maltophilia strains resistant to ≥ 2 antibiotic classes, using Rose Bengal at concentrations ranging from 1 to 100 µM, activated by green (530 nm) and blue (470 nm) diode lasers at fluences of 2 and 5 J/cm². The expression of the smeDEF gene was assessed using real-time PCR. Antibiotic susceptibility testing revealed resistance rates of 6.4% to levofloxacin, 4.3% to minocycline, and 3.6% to trimethoprim-sulfamethoxazole (TMP/SMX). Four S. maltophilia isolates showed resistance to ≥ 2 antibiotic classes. aPDT with Rose Bengal activated by blue and green diode laser light inhibited growth in all but one resistant isolate, which grew under green light at a dose of 2 j/cm². Real-time PCR analysis revealed a 1.4-fold downregulation of the smeDEF gene in the S. maltophilia isolate resistant to five antibiotic classes following aPDT treatment, compared to the control. The current research discloses the increasing pattern of antibiotic resistance in S. maltophilia isolates in Iran. Yet, TMP/SMX is counted as the first option for the treatment of S. maltophilia infections. Furthermore, our findings suggest that, aPDT is an effective therapeutic approach for treating antibiotic-resistant S. maltophilia isolates.