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The UDP‐GalNAcA biosynthesis genes gna ‐ gne2 are required to maintain cell envelope integrity and in vivo fitness in multi‐drug resistant Acinetobacter baumannii
Author(s) -
Crépin Sébastien,
Ottosen Elizabeth N.,
Chandler Courtney E.,
Sintsova Anna,
Ernst Robert K.,
Mobley Harry L. T.
Publication year - 2020
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14407
Subject(s) - biology , acinetobacter baumannii , mutant , cell envelope , microbiology and biotechnology , biosynthesis , in vivo , gene , antibiotics , genetics , bacteria , escherichia coli , pseudomonas aeruginosa
Summary Acinetobacter baumannii infects a wide range of anatomic sites including the respiratory tract and bloodstream. Despite its clinical importance, little is known about the molecular basis of A . baumannii pathogenesis. We previously identified the UDP‐ N ‐acetyl‐ d ‐galactosaminuronic acid (UDP‐GalNAcA) biosynthesis genes, gna ‐ gne2 , as being critical for survival in vivo . Herein, we demonstrate that Gna‐Gne2 are part of a complex network connecting in vivo fitness, cell envelope homeostasis and resistance to antibiotics. The ∆ gna ‐ gne2 mutant exhibits a severe fitness defect during bloodstream infection. Capsule production is abolished in the mutant strain, which is concomitant with its inability to survive in human serum. In addition, the ∆ gna ‐ gne2 mutant was more susceptible to vancomycin and unable to grow on MacConkey plates, indicating an alteration in cell envelope integrity. Analysis of lipid A by mass spectrometry showed that the hexa‐ and hepta‐acylated species were affected in the gna ‐ gne2 mutant. Finally, the ∆ gna ‐ gne2 mutant was more susceptible to several classes of antibiotics. Together, this study demonstrates the importance of UDP‐GalNAcA in the pathobiology of A . baumannii . By interrupting its biosynthesis, we showed that this molecule plays a critical role in capsule biosynthesis and maintaining the cell envelope homeostasis.