The UDP‐GalNAcA biosynthesis genes gna gna ‐ gne2 gne2 are required to maintain cell envelope integrity and in vivo in vivo fitness in multi‐drug resistant Acinetobacter baumannii Acinetobacter baumannii

摘要

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.