Arginine utilization in Acinetobacter baumannii is essential for pneumonia pathogenesis and is regulated by virulence...

Nutrient availability in infection niches and the ability of bacterial pathogens to alter their metabolic landscape to utilize diverse carbon sources play a major role in determining the extent of pathogenesis. The vertebrate lung is rich in amino acids, such as arginine, which are available to the pathogens as a nutrient source to establish infection. Arginine is also used by the host nitric oxide synthase to synthesize nitric oxide, which is used against invading pathogens and for lung tissue repair. In this study, we have focused on the arginine catabolic pathway and its importance in the pathophysiology of Acinetobacter baumannii, a nosocomial pathogen, which is one of the major causes of ventilator-associated pneumonia, catheter-associated urinary tract infection, and so on. We show that the arginine succinyltransferase (AST) pathway is the predominant arginine catabolic pathway in A. baumannii. The genes of the AST pathway are arranged in an operon and are conserved in Acinetobacter spp. We show that the deletion mutant of the AST pathway failed to utilize arginine as a carbon source, and its virulence was severely compromised in an in vivo murine pneumonia infection model. We identified GacA as the positive regulator of the AST operon in A. baumannii, which is different from other bacterial pathogens. Our study highlights the importance of arginine utilization in the pathophysiology and virulence of A. baumannii. Owing to its importance in the pathophysiology of A. baumannii, the arginine catabolic pathway can further be investigated to assess its suitability as an antibacterial drug target.