Universität zu Köln

D'Souza, Roshan, Pinto, Naina A., Higgins, Paul G. ORCID: 0000-0001-8677-9454, Byun, Jung-Hyun ORCID: 0000-0001-5909-5807, Cho, Young Lag, Choi, Jong Rak and Yong, Dongeun (2019). Phenotypic and Genotypic Characterization of Acinetobacter spp. Panel Strains: A Cornerstone to Facilitate Antimicrobial Development. Front. Microbiol., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-302X

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Abstract

Acinetobacter spp. have emerged as significant pathogens causing nosocomial infections. Treatment of these pathogens has become a major challenge to clinicians worldwide, due to their increasing tendency to antibiotic resistance. To address this, much revenue and technology are currently being dedicated toward developing novel drugs and antibiotic combinations to combat antimicrobial resistance. To address this issue, we have constructed a panel of Acinetobacter spp. strains expressing different antimicrobial resistance determinants such as narrow spectrum beta-lactamases, extended-spectrum beta-lactamases, OXA-type-carbapenemase, metallo-beta-lactamase, and over-expressed AmpC beta-lactamase. Bacterial strains exhibiting different resistance phenotypes were collected between 2008 and 2013 from Severance Hospital, Seoul. Antimicrobial susceptibility was determined according to the CLSI guidelines using agar dilution method. Selected strains were sequenced using Ion Torrent PGM system, annotated using RAST server and analyzed using Geneious pro 8.0. Genotypic determinants, such as acquired resistance genes, changes in the expression of efflux pumps, mutations, and porin alternations, contributing to the relevant expressed phenotype were characterized. Isolates expressing ESBL phenotype consisted of bla(PER-1) gene, the overproduction of intrinsic AmpC beta-lactamase associated with ISAba1 insertion, and carbapenem resistance associated with production of carbapenem-hydrolyzing Ambler class D beta-lactamases, such as OXA-23, OXA-66, OXA-120, OXA-500, and metallo-beta-lactamase, SIM-1. We have analyzed the relative expression of Ade efflux systems, and determined the sequences of their regulators to correlate with phenotypic resistance. Quinolone resistance-determining regions were analyzed to understand fluoroquinolone-resistance. Virulence factors responsible for pathogenesis were also identified. Due to several mutations, acquisition of multiple resistance genes and transposon insertion, phenotypic resistance decision scheme for for evaluating the resistance proved inaccurate, which highlights the urgent need for modification to this scheme. This complete illustration of mechanism contributing to specific resistance phenotypes can be used as a target for novel drug development. It can also be used as a reference strain in the clinical laboratory and for the evaluation of antibiotic efficacy for specific resistance mechanisms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code D'Souza, Roshan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinto, Naina A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED Byun, Jung-Hyun UNSPECIFIED orcid.org/0000-0001-5909-5807 UNSPECIFIED Cho, Young Lag UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Jong Rak UNSPECIFIED UNSPECIFIED UNSPECIFIED Yong, Dongeun UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-153391
DOI:	10.3389/fmicb.2019.00559
Journal or Publication Title:	Front. Microbiol.
Volume:	10
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-302X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SPECTRUM-BETA-LACTAMASE; OUTER-MEMBRANE PROTEIN; MULTIDRUG-RESISTANCE; CARBAPENEM RESISTANCE; EFFLUX PUMPS; MOLECULAR EPIDEMIOLOGY; AMINOGLYCOSIDE-RESISTANCE; BAUMANNII INFECTIONS; NUCLEOTIDE-SEQUENCE; BIOFILM FORMATION Multiple languages Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15339