Camila Azevedo Antunes, Emily C A Goodall, Ian R Henderson, David Wild, Alexander Mehltretter, Philipp Ott, Markus Hölzl, Lisa Ott, Gerald Seidel, Andreas Burkovski
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Genome-wide high-throughput transposon mutagenesis unveils key factors for acidic pH adaptation of Corynebacterium diphtheriae.
Corynebacterium diphtheriae, a notable pathogen responsible for the life-threatening disease diphtheria, encounters harsh intracellular environments within the host, particularly within macrophages where acidic conditions prevail. To elucidate the genetic and molecular mechanisms underlying its acid stress response, we employed a Transposon Directed Insertion-site Sequencing approach. This comprehensive study identified crucial genes and pathways facilitating C. diphtheriae's survival at low pH. In subsequent experiments, the Ktr potassium transport system was identified as a putative key factor for maintaining pH homeostasis and growth under acidic stress. A ktrBA deletion strain exhibited significantly reduced growth at pH 5, which could be restored by ktrBA expression in trans. The deletion strain showed unchanged uptake and survival in macrophages compared to the wild-type, indicating that the Ktr system is not crucial for the survival of C. diphtheriae in phagocytes. These findings advance our understanding of C. diphtheriae's pathophysiology, further delineating the intricate survival strategies of C. diphtheriae in hostile environments.
期刊介绍:
We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms.
Topics include but are not limited to:
Antimicrobials and antimicrobial resistance
Bacteriology and parasitology
Biochemistry and biophysics
Biofilms and biological systems
Biotechnology and bioremediation
Cell biology and signalling
Chemical biology
Cross-disciplinary work
Ecology and environmental microbiology
Food microbiology
Genetics
Host–microbe interactions
Microbial methods and techniques
Microscopy and imaging
Omics, including genomics, proteomics and metabolomics
Physiology and metabolism
Systems biology and synthetic biology
The microbiome.