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Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo
Ist Teil von
Antimicrobial agents and chemotherapy, 2019-03, Vol.63 (3)
Ort / Verlag
United States: American Society for Microbiology
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
Colistin resistance in
is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of
isolates displaying an increase in colistin MICs. A mutation in
was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of
was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of
carrying the short amino acid deletion ΔL9-G12 into a
knockout strain resulted in increased
expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the
homologue
and a point mutation in IS
upstream of
were associated with colistin resistance and increased
expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a
infection model. Although the mutations in
were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.