An Acinetobacter baumannii acyltransferase represses pilin production to maintain energy homeostasis and overcome nutritional immunity

Respiratory infections are the fourth leading cause of death globally. Acinetobacter baumannii is a significant cause of ventilator-associated pneumonia and antibiotic-resistant attributable deaths worldwide. Iron is an essential nutrient; vertebrates exploit this by sequestering iron from invading pathogens in a process termed nutritional immunity. The competition for iron is a crucial determinant of A. baumannii infection severity and outcome. Here, we have discovered an A. baumannii acyltransferase that we have named AimS. AimS promotes fitness in low iron environments and contributes to A. baumannii surviving nutritional immunity encountered during pneumonia. Mechanistic studies revealed that AimS impacts fitness through maintenance of cellular ATP via repression of pili production and biofilm formation, key virulence phenotypes, through a transcriptional regulator we have named CsuR. These findings reveal an energy sparing mechanism that A. baumannii employs to regulate pathogenesis and ensure energy availability, enabling the pathogen to overcome nutritional immunity at the host-pathogen interface.