Investigating the Effect of Xylitol on ompK36 Overexpression, Increased Meropenem Susceptibility, and Antibiofilm Activity in a Carbapenem-Resistant Clinical Strain of Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae poses a significant public health threat due to limited therapeutic options. This study investigated the potential of xylitol, a sugar alcohol, to enhance meropenem activity and combat biofilms in a clinical carbapenem-resistant K. pneumoniae strain (Kp5) and a standard susceptible strain (K. pneumoniae subsp. pneumoniae ATCC 13883). The synergistic activity between xylitol and meropenem in inhibiting bacterial growth was assessed using a two-dimensional checkerboard assay. Real-time PCR was performed to assess the effect of xylitol on the expression of the porin gene ompK36, a key determinant of carbapenem entry and resistance in K. pneumoniae. Moreover, the microtiter plate assay was used to evaluate its antibiofilm efficacy. Results showed that xylitol exhibited a synergistic effect with meropenem, leading to a significant reduction in the meropenem minimum inhibitory concentration (MIC) in both strains. Notably, the meropenem MIC for the Kp5 strain was reduced by up to 32-fold in the presence of xylitol. Exposure to xylitol alone induced a significant upregulation of ompK36 expression in both strains, suggesting that increased porin gene expression may enhance meropenem activity. Furthermore, xylitol demonstrated potent, concentration-dependent antibiofilm activity, both inhibiting biofilm formation and eradicating established biofilms. This approach offers a promising strategy for repurposing a safe and readily available compound to address a critical aspect of antimicrobial resistance.