Human umbilical-cord mesenchymal stem cells inhibit bacterial growth and alleviate antibiotic resistance in neonatal imipenem-resistant Pseudomonas aeruginosa infection

Human umbilical-cord mesenchymal stem cells (hUCMSCs) are a safe and convenient source of MSCs and have shown beneficial effects in neonatal infection and sepsis animal models. However, the factors leading to improved outcomes are still unclear. The aim of this study was to investigate the antibacterial effect and regulation of antimicrobial resistance of hUCMSCs. We separated imipenem-resistant Pseudomonas aeruginosa (PA) from neonates and incubated it with hUCMSCs as well as their culture medium. Assessment of direct inhibition of bacterial growth was done by counting CFUs. The concentration of antibacterial peptides in the culture medium of hUCMSCs was measured. Standard PA was inoculated with a sub-inhibitory concentration of imipenem with and without hUCMSC conditioned medium and antimicrobial peptides. The sensitivity to imipenem was detected until PA showed resistance to imipenem. Outer membrane protein (OprD2) mRNA expression in PA before and after the induction of imipenem resistance was analysed. We found that HUCMSCs possessed direct antimicrobial properties against bacteria and could alleviate antibiotic resistance via reserving OprD2 expression in PA.