Clinical characterization and the β‐lactamase profiles of medically important Aeromonas genospecies in Taiwan

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Student thesis: Doctoral Thesis

Abstract

Aeromonas species, an aquatic gram-negative bacillus, distributes globally and ubiquitously in the nature environment. The recently reported novel species, Aeromonas dhakensis (formerly named A. aquariorum), has been found to be implicated in a variety of human diseases. However, little is known about the prevalence and clinical features of A. dhakensis bacteremia, and the knowledge of β-lactamase genes harbored in it is limited. The aims of this study were to investigate molecular epidemiology and clinical characterization of Aeromonas bacteremia and the distributions of β-lactamase genes in different Aeromonas genospecies in Taiwan, with emphasis on a novel species, A. dhakensis.
First, our molecular epidemiological surveillance of 153 patients with monomicrobial Aeromonas bacteremia during 2004 to 2011 at a medical center in southern Taiwan revealed that A. dhakensis, along with A. veronii and A. caviae, were the three major species causing Aeromonas bacteremia. As the cases of A. hydrophila and A. veronii bacteremia, about half of the patients with A. dhakensis bacteremia had liver cirrhosis. Oral ingestion is one of the possible routes to acquire A. dhakensis infections. Clinically, A. dhakensis was found to be the most virulent species, as demonstrated as an independent risk factor for 14-day sepsis-related mortality. A cefotaxime-resistant A. dhakensis isolate and an imipenem-resistant A. dhakensis isolate emerged from patients receiving ceftazidime and ertapenem therapy, respectively.
With the knowledge of whole genome sequencing of an A. dhakensis strain (A. aquariorum) AAK1, A. dhakensis is found to intrinsically carry three chromosomal genes encoding Ambler class B β-lactamase (CphA metallo-β-lactamase, carbapenemase), class C β-lactamase (AmpC β-lactamase, cephalosporinase), and class D β-lactamase (penicillinase). We further characterized and reported the novel AmpC gene in A. dhakensis, blaAQU-1. Transcriptome analyses revealed that these three β-lactamases are co-regulated by a two component regulatory system. The distribution of chromosomal class B, C, D β-lactamase genes among aeromonads was species-specific. CphA MBL genes were present in all A. dhakensis, A. hydrophila, and A. veronii isolates, while AmpC β-lactamase genes were found in all A. dhakensis (blaAQU-1) and A. caviae (blaMOX-like genes) isolates. The acquired resistance, for example, acquisition of a gene encoding extended-spectrum β-lactamase (ESBL), was also found among aeromonads. Of 156 blood isolates between 2004 and 2008, 4 (2.6%) isolates expressed the ESBL phenotypes.
Because these β-lactamases cannot be readily detected by the routine antimicrobial susceptibility testing used in the clinical microbiological laboratories, an understanding of the β-lactamase types in major Aeromonas genospecies is important. Our study results may add to the understanding towards appropriate antimicrobial therapy for Aeromonas infections.
Date of Award2014
Original languageEnglish
SupervisorMing Chung Chang (Supervisor), Wen-Chien Ko (Supervisor), Po Ren Hsueh (Supervisor) & Pei-Jane Tsai (Supervisor)

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