Hypertonic glucose inhibits growth and attenuates virulence factors of multidrug-resistant Pseudomonas aeruginosa

Abstract

Background: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections, such as diabetic foot infections, and further exacerbates the treatment options and cost of such conditions. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in wounds. However, the action of hypertonic glucose on bacterial pathogens that infect wounds is unclear. In this study, we investigated the inhibitory effects of hypertonic glucose on multidrug-resistant P. aeruginosa strains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused by P. aeruginosa. Results: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the reference P. aeruginosa PAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa clinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors in P. aeruginosa. The expression of major quorum sensing genes (lasI, lasR, rhlI, and rhlR) in P. aeruginosa were all downregulated in response to hypertonic glucose treatment. In a Galleria mellonella larvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected by P. aeruginosa strains (3/5). Conclusions: Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa, as well as reduced the production of virulence factors and quorum sensing gene expression. Further studies that investigate hypertonic glucose therapy should be considered in treating chronic wound infections.

Evaluation of the antibacterial, antibiofilm, and anti-virulence effects of acetic acid and the related mechanisms on colistin-resistant Pseudomonas aeruginosa

“…The effects of AA on the expression levels of P. aeruginosa QS circuit genes (i.e., lasR, rhlR, rhlI, rhlA, and pqsA) and T3SS circuit genes (i.e., exoT, exoS, exsA, and exoY) and the flagellin gene (fliC) were evaluated by qRT-PCR, as described previously [35][36][37][38]. P. aeruginosa TL1671 and TL2314 was incubated in fresh LB broth at 37℃ under 180 rpm until reaching the logarithmic growth phase (OD 600 0.5-0.6).…”

Xylitol Inhibits Growth and Blocks Virulence in Serratia marcescens

“…The expression of P. aeruginosa QS genes was down-regulated in glucose hypertonic concentration (20%). Moreover, the administration of hypertonic glucose (20%) increased the survival rates of Galleria mellonella larvae from P. aeruginosa [ 67 ]. This may suggest a role for the osmotic stress of xylitol in attenuation of the virulence of S. marcescens .…”

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa

“…The first one was injected at 200 mg/ml, a concentration higher than the concentration used for GM-50 in the present study (100 µM). Clofoctol was used at 100 µM, but it affects another PA QS-system, the Pqs, regulated by quinolones ( D’Angelo et al, 2018 ; Chen et al, 2020 ). Since GM-50 did not alter bacterial growth rates or exert direct antimicrobial activity, our results suggest that inhibiting AHL-dependent Rhl circuits decreases pyocyanin, elastase B, rhamnolipids, and swarming motility.…”