mgrB inactivation confers enhanced pathogenicity and immune evasion over mcr-1 expression in colistin-resistant Klebsiella pneumoniae.

Abstract

Colistin is one of the last treatment options against human infections caused by multi-drug resistant Klebsiella pneumoniae. Colistin resistant K. pneumoniae arises through modifying bacterial lipopolysaccharide (LPS) via two mechanisms: the mgrB inactivation on chromosome and mcr-1 expression - usually plasmid-mediated. Notably, chromosomal-mediated resistance is more common in naturally-occurring clinical K. pneumoniae than plasmid-borne resistance. Herein we demonstrated that K. pneumoniae strain with a mutant mgrB (ΔmgrB) gene exhibited increased pathogenicity compared to those carrying mcr-1, as evidenced in Galleria mellonella and murine bacteraemia model. Strain possessing ΔmgrB showed higher mortality rate, greater bacterial accumulation, and increased damage to host tissue. Although both ΔmgrB and mcr-1 impose fitness cost on K. pneumoniae and enhance bacterial evasion from phagocytosis, ΔmgrB mediated greater bacterial resistance to host defence peptides than mcr-1, providing an evolutionary advantage. These findings indicated distinct features of mgrB-inactivated K. pneumoniae and mcr-1-positive K. pneumoniae in host immunity responses, and promote understanding of how antibiotic-resistant determinants influence host-pathogens interactions.