L-Serine enables reducing the virulence of Acinetobacter baumannii and modulating the SIRT1 pathway to eliminate the pathogen

Abstract

ABSTRACT The emergence of high-virulent Acinetobacter baumannii strains increases the mortality of patients and seriously affects their prognosis, which motivates us to explore novel ways to control such infections. In this study, gas chromatography–mass spectrometry was adopted to explore the metabolic difference between high- and low-virulent A. baumannii strains, and the decreased L-serine levels were identified as the most crucial biomarker in low-virulent A. baumannii strains. In vitro , L-serine reduced the virulence of A. baumannii to Beas 2B cells and inhibited the activation of NLRP3 inflammasome via decreasing the generation of ROS and mtROS and the release of inflammatory cytokines (IL-18 and IL-1β) through upregulating SIRT1. In vivo , the Galleria mellonella model was adopted. L-serine downregulated the levels of virulence genes ( ompA , carO , and omp 33-36), reduced the mortality of A. baumannii to G. mellonella , and decreased the blacking speed as well as the degree of G. mellonella after infection. Taken together, we found that L-serine can reduce the virulence of A. baumannii and enhance the host’s defense against the pathogen, providing a novel strategy for the treatment of infections caused by A. baumannii . IMPORTANCE Acinetobacter baumannii has become one of the most common and severe opportunistic pathogens in hospitals. The high-virulent A. baumannii strains pose a great threat to patients and increase the risk of nosocomial infection. However, the mechanism of virulence in A. baumannii is still not well understood. In the present study, we identified potential biomarkers in low-virulent A. baumannii strains. Our analysis revealed the effect of L-serine on reducing the virulence of A.baumannii . This discovery suggests that targeting L-serine could be a promising strategy for the treatment or adjunctive treatment of A. baumannii infections. The development of treatments targeting virulence may provide a substitute for the increasingly failed traditional antibacterial treatment.