LAPORAN PENELITIAN

Disertasi - Mechanisms of Colistin Resistance in Acinetobacter baumannii

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Abstract

Colistin-resistant Acinetobacter baumannii is a threat worldwide since it leads to
limited treatment options in clinical settings. We investigated seven colistin-resistant A.
baumannii out of 452 carbapenem-resistant isolates (1.55%) from Taipei Medical
University Hospital (TMUH) during 2017 to 2018. In this study, amino acid substitutions
in sensor kinase PmrB were major mechanism causing colistin resistance. Mutations
found in this study included three reported mutations (P233S, R263H, Q270P) in the
histidine kinase domain of PmrB, and two novel mutations, A138S and Δ187. Mutations
in PmrB have been known to auto-regulate the expression of genes associated with
modification on lipid A through PmrA. These genes, including pmrC, eptA, and naxD,
were overexpressed in all seven isolates. An LpxD mutation (K117E), locating at the
lipid-binding site, was detected in one isolate containing a different lipopolysaccharide
pattern. No loss of fitness costs in vitro and less biofilm production were observed in all
isolates. According to the population analysis profile, one isolate showed heteroresistance
to colistin. Four isolates were significantly higher virulence than a reference using
Galleria mellonella larvae as the infection model. In addition, ten colistin-resistant A.
baumannii from the Taiwan Surveillance Antimicrobial Resistance (TSAR) program
during 2012 to 2018 were evaluated their resistance mechanisms on colistin.
Interestingly, unlike TMUH isolates, only two of ten TSAR isolates contained two novel
PmrB mutations (F222Y and S61R). Overexpression of pmrC was only found in the
isolate with a PmrB mutation, F222Y. This study showed that the PmrB mutation is the
leading cause of colistin resistance in A. baumannii from TMUH. However, the majority
of TSAR isolates showed no PmrB mutation and overexpression of pmrC.

Keywords: Acinetobacter baumannii, colistin resistance, virulence,
Phosphoethanolamine transferase, biofilm, heteroresistance, Galleria mellonella

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Informasi Detail

Judul Seri

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No. Panggil

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Penerbit

Taiwan : Taipei Medical University., 2021

Deskripsi Fisik

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Bahasa

Indonesia

ISBN/ISSN

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Klasifikasi

NONE

Tipe Isi

Dokumen Online

Tipe Media

Link Internet Online

Tipe Pembawa

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Edisi

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Subjek

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Info Detail Spesifik

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Pernyataan Tanggungjawab

Noor Andryan Ilsan, Ph.D

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