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

Abstract
Background Pseudomonas aeruginosais 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-resistantP. aeruginosastrains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused byP. aeruginosa. Results Four multidrug-resistantP. aeruginosaclinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the referenceP. aeruginosaPAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility ofP. aeruginosaclinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors inP. aeruginosa. The expression of major quorum sensing genes (lasI,lasR,rhlI, andrhlR) inP. aeruginosawere all downregulated in response to hypertonic glucose treatment. In aGalleria mellonellalarvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected byP. aeruginosastrains (3/5). Conclusions Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility ofP. 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.
Funding Information
  • Natural Science Foundation of Zhejiang Province (LY18H190004)
  • Health Department of Zhejiang Province of the People's Republic of China (2018KY123)