MgrB-Dependent Colistin Resistance in Klebsiella pneumoniae Is Associated with an Increase in Host-to-Host Transmission
Andrew S. Bray, Richard D. Smith, Andrew W. Hudson, Giovanna E. Hernandez, Taylor M. Young, Hannah E. George, Robert K. Ernst, M. Ammar Zafar
Abstract
The biological cost associated with colistin resistance in Klebsiella pneumoniae was examined using a murine model of K. pneumoniae gut colonization and fecal-oral transmission. A common mutation resulting in colistin resistance in K. pneumoniae is a loss-of-function mutation of the small regulatory protein MgrB that regulates the two-component system PhoPQ. Even though colistin resistance in K. pneumoniae comes with a fitness defect in gut colonization, it increases bacterial survival outside the host enabling it to transmit more effectively to a new host. The enhanced survival is dependent upon the accumulation of RpoS and dysregulation of the PhoPQ. Hence, our study expands our understanding of the underlying molecular mechanism contributing to the transmission of colistin-resistant K. pneumoniae.