Abstract
Summary Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi‐drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon‐sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc‐GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract.
Highlights
Worldwide, 700,000 deaths are associated with multidrug resistant infections per year
Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream
In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis
Summary
700,000 deaths are associated with multidrug resistant infections per year. A. baumannii, a gram-negative, encapsulated bacterium, has emerged as a leading nosocomial pathogen, in intensive care units specializing in respiratory care, trauma and burns (Wong et al, 2017). This bacterium infects a wide range of anatomic sites including the respiratory tract, bloodstream, wounds, urinary tract and meninges (Wong et al, 2017). Alarming is its mortality rate, which is about 50% and 36% for ventilator-associated pneumonia and bloodstream infections respectively (Fagon et al, 1996; Garnacho et al, 2003; Seifert et al, 1995; Wisplinghoff et al, 2004)
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