ppGpp signaling plays a critical role in virulence of .

, a major nosocomial pathogen, survives in diverse hospital environments, and its multidrug resistance is a major concern. The ppGpp-dependent stringent response mediates the reprogramming of genes with diverse functions in several bacteria. We investigated whether ppGpp is involved in pathogenesis by examining biofilm formation, surface motility, adhesion, invasion, and mouse infection studies. Transcriptome analysis of early stationary phase cultures revealed 498 differentially-expressed genes (≥ 2-fold change) in a ppGpp-deficient strain; 220 and 278 genes were up and downregulated, respectively. C operon expression, important in pilus biosynthesis during early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings suggest that ppGpp signaling influences biofilm formation, surface motility, adherence, and virulence. We showed the association between ppGpp and pathogenicity in for the first time; ppGpp may be a novel antivirulence target in