[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Colistin-resistance-mediated bacterial surface modification sensitizes phage infection
Guijuan Hao, Annie I. Chen, Ming Liu, Haijian Zhou, Marisa Egan, Xiaoman Yang, Biao Kan, Hui Wang, Mark Goulian, Jun Zhu
Colistin is a drug of last resort for the treatment of many multidrug resistant Gram-negative bacteria, including Klebsiella pneumoniae. However, bacteria readily acquire resistance to this antibiotic via lipopolysaccharide modifications caused by spontaneous mutations or from enzymes acquired by lateral gene transfer. The fitness cost associated with these modifications remains poorly understood. In this study, we show that colistin-resistant K. pneumoniae are more susceptible to killing by a newly isolated lytic phage than the colistin sensitive parent strain. We observe this behavior for colistin-resistance conferred by a horizontally transferred mcr-1 containing plasmid and also from the inactivation of the chromosomal gene mgrB. By measuring zeta potentials, we found that the phage particles were negatively charged at neutral pH and that colistin-resistant bacteria had less negative zeta potentials than did wildtype. These results suggest that the decreased negative surface charge of colistin-resistant cells lowers the electrostatic repulsion between the phage and bacteria, thereby promoting phage adherence and subsequent infection. To further explore this, we tested the effect of phage treatment on K. pneumoniae growing in several different environments. We found that colistin-resistant cells were more susceptible to phage than were the wildtype cells when growing in biofilms or infected moth larvae and when colonizing the mammalian gut. A better understanding of these fitness costs may lead to new treatment approaches that minimize the emergence and spread of colistin-resistant pathogens in human and environmental reservoirs.
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Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Klebsiella pneumoniae; Bacteriophages.