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Molecular Mechanisms of Colistin Resistance Among Pandrug-Resistant Isolates of Acinetobacter baumannii with High Case-Fatality Rate in Intensive Care Unit Patients
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Molecular Mechanisms of Colistin Resistance Among Pandrug-Resistant Isolates of Acinetobacter baumannii with High Case-Fatality Rate in Intensive Care Unit Patients
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Molecular Mechanisms of Colistin Resistance Among Pandrug-Resistant Isolates of Acinetobacter baumannii with High Case-Fatality Rate in Intensive Care Unit Patients
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Journal Article
Molecular Mechanisms of Colistin Resistance Among Pandrug-Resistant Isolates of Acinetobacter baumannii with High Case-Fatality Rate in Intensive Care Unit Patients
2018
Overview
Colistin is considered a last-hope antibiotic against extensively drug-resistant isolates of
Acinetobacter baumannii
. Resistance to colistin has been rarely reported for
A. baumannii
. Genetic alterations in the PmrA-PmrB two-component system and lipid A biosynthesis genes may be associated with colistin resistance. We investigated molecular mechanisms of colistin resistance in three clinical colistin-resistant (ColR) and two colistin-susceptible (ColS)
A. baumannii
isolates. A ColR mutant was generated
in vitro
by repetitive drug exposure. The
pmrA
,
pmrB
,
lpxA
,
lpxC
, and
lpxD
genes were amplified and sequenced. To evaluate association between colistin resistance and upregulation of
pmrCAB
operon, transcriptional level of the
pmrC
gene encoding for lipid A phosphoethanolamine (PEtN) transferase was quantified by reverse transcription quantitative PCR (RT-qPCR) analysis. All clinical and
in vitro-
selected ColR isolates harbored at least one point mutation in the
pmrB
gene, including A142V, P233S, T235I, and A227V substitutions as well as duplication of H325. No alteration was found in the
pmrA
and other amino acid substitutions identified in the
pmrB
as well as
lpx
genes did not seem to be involved in colistin resistance as they were found in both ColS and ColR isolates. RT-qPCR analysis revealed a correlation between colistin resistance and
pmrC
overexpression. Specific alterations in the PmrB, linked to overproduction of PEtN transferase, triggered colistin resistance in the studied
A. baumannii
isolates.
Publisher
Mary Ann Liebert, Inc., publishers,SAGE Publications,Mary Ann Liebert, Inc
Subject
/ Acinetobacter baumannii - drug effects
/ Acinetobacter baumannii - genetics
/ Acinetobacter Infections - microbiology
/ Amino Acid Substitution - genetics
/ Anti-Bacterial Agents - pharmacology
/ Bacterial Proteins - genetics
/ Colistin
/ Drug Resistance, Bacterial - genetics
/ Enzymes
/ Genes
/ Humans
/ Kinases
/ Lipid A
/ Lipids
/ Microbial Sensitivity Tests - methods
/ Mutation
/ Studies
