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, Ian R. Henderson2
, David Wild1, Alexander Mehltretter1, Philipp Ott1, Markus Hölzl1, Lisa Ott1, Gerald Seidel1 and Andreas Burkovski1
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.
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