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2017 ; 9
(4
): 430-447
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A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host
defences and promotes virulence
#MMPMID28202493
Kidd TJ
; Mills G
; Sá-Pessoa J
; Dumigan A
; Frank CG
; Insua JL
; Ingram R
; Hobley L
; Bengoechea JA
EMBO Mol Med
2017[Apr]; 9
(4
): 430-447
PMID28202493
show ga
Klebsiella pneumoniae is an important cause of multidrug-resistant infections
worldwide. Recent studies highlight the emergence of multidrug-resistant
K. pneumoniae strains which show resistance to colistin, a last-line antibiotic,
arising from mutational inactivation of the mgrB regulatory gene. However, the
precise molecular resistance mechanisms of mgrB-associated colistin resistance
and its impact on virulence remain unclear. Here, we constructed an mgrB gene
K. pneumoniae mutant and performed characterisation of its lipid A structure,
polymyxin and antimicrobial peptide resistance, virulence and inflammatory
responses upon infection. Our data reveal that mgrB mutation induces
PhoPQ-governed lipid A remodelling which confers not only resistance to
polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial
peptide susceptibility and attenuating early host defence response activation.
Overall, our findings have important implications for patient management and
antimicrobial stewardship, while also stressing antibiotic resistance development
is not inexorably linked with subdued bacterial fitness and virulence.