The Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc Limitation.

Abstract

is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health Organization to declare a "Priority 1: Critical" pathogen, for which the development of novel antimicrobials is desperately needed. Zinc (Zn) is an essential nutrient that pathogenic bacteria, including , must acquire from their hosts in order to survive. Consequently, vertebrate hosts have defense mechanisms to sequester Zn from invading bacteria through a process known as nutritional immunity. Here, we describe a ptake (Znu) system that enables to overcome this host-imposed Zn limitation. The Znu system consists of an inner membrane ABC transporter and an outer membrane TonB-dependent receptor. Strains of lacking any individual Znu component are unable to grow in Zn-starved conditions, including in the presence of the host nutritional immunity protein calprotectin. The Znu system contributes to Zn-limited growth by aiding directly in the uptake of Zn into cells and is important for pathogenesis in murine models of infection. These results demonstrate that the Znu system allows to subvert host nutritional immunity and acquire Zn during infection.