The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii

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 und...

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Bibliographic Details
Published in:Molecular microbiology 2018-09, Vol.109 (6), p.745-762
Main Authors: Crépin, Sébastien, Ottosen, Elizabeth N., Peters, Katharina, Smith, Sara N., Himpsl, Stephanie D., Vollmer, Waldemar, Mobley, Harry L. T.
Format: Article
Language:English
Subjects:
Acinetobacter baumannii
Acinetobacter baumannii - genetics
Acinetobacter baumannii - metabolism
Acinetobacter baumannii - pathogenicity
Acinetobacter Infections - microbiology
Acinetobacter Infections - pathology
Animals
Antimicrobial Cationic Peptides - pharmacology
Antimicrobial peptides
Bacteremia
Cationic antimicrobial peptides
Cell Membrane - metabolism
Cell surface
Cell walls
Colonization
Complement System Proteins - immunology
Deactivation
Drug resistance
Female
Fitness
Glycosyltransferases - genetics
Glycosyltransferases - metabolism
High-Throughput Nucleotide Sequencing
Homeostasis
Hospitals
Inactivation
Mice
Mice, Inbred CBA
Muramic Acids - metabolism
Neutropenia
Nosocomial infection
Pathogenesis
Peptides
Peptidoglycan - metabolism
Peptidoglycans
Pili
Respiratory tract
Stress, Physiological
Virulence
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Summary: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. Despite its clinical importance, relatively little is known about the molecular basis of Acinetobacter baumannii pathogenesis. Using a transposon‐sequencing (Tn‐Seq) screen and the mouse model of bloodstream infection, we identified the lytic transglycosylase MltB as being a critical fitness factor in A. baumannii. In this study, we showed that MltB is part of a complex network connecting resistance to stresses, cell envelope homeostasis, biogenesis of pili and in vivo fitness.
ISSN:0950-382X
1365-2958
DOI:10.1111/mmi.14000