The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15

Abstract Great efforts have been made to limit the transmission of carbapenemase-producing Enterobacteriaceae (CPE), however, the intestinal reservoir of these strains and its modulation by various antibiotics remain largely unexplored. Our aim was to assess the effects of antibiotic administration...

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Autores principales:	Balázs Stercz, Ferenc B. Farkas, Ákos Tóth, Márió Gajdács, Judit Domokos, Viola Horváth, Eszter Ostorházi, Nóra Makra, Béla Kocsis, János Juhász, Balázs Ligeti, Sándor Pongor, Dóra Szabó
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3fd347bee6b843aeb47422a2bdcfe09c
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spelling	oai:doaj.org-article:3fd347bee6b843aeb47422a2bdcfe09c2021-12-02T11:39:48ZThe influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST1510.1038/s41598-021-85766-62045-2322https://doaj.org/article/3fd347bee6b843aeb47422a2bdcfe09c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85766-6https://doaj.org/toc/2045-2322Abstract Great efforts have been made to limit the transmission of carbapenemase-producing Enterobacteriaceae (CPE), however, the intestinal reservoir of these strains and its modulation by various antibiotics remain largely unexplored. Our aim was to assess the effects of antibiotic administration (ampicillin, ceftazidime, ciprofloxacin) on the establishment and elimination of intestinal colonization with a CTX-M-15 ESBL and OXA-162 carbapenemase producing Klebsiella pneumoniae ST15 (KP5825) in a murine (C57BL/6 male mice) model. Whole genome sequencing of KP5825 strain was performed on an Illumina MiSeq platform. Conjugation assays were carried out by broth mating method. In colonization experiments, 5 × 106 CFU of KP5825 was administered to the animals by orogastric gavage, and antibiotics were administered in their drinking water for two weeks and were changed every day. The gut colonization rates with KP5825 were assessed by cultivation and qPCR. In each of the stool samples, the gene copy number of bla OXA-162 and bla CTX-M-15 were determined by qPCR. Antibiotic concentrations in the stool were determined by high pressure liquid chromatography and a bioanalytical method. The KP5825 contained four different plasmid replicon types, namely IncFII(K), IncL, IncFIB and ColpVC. IncL (containing the bla OXA-162 resistance gene within a Tn1991.2 genetic element) and IncFII(K) (containing the bla CTX-M-15 resistance gene) plasmids were successfully conjugated. During ampicillin and ceftazidime treatments, colonization rate of KP5825 increased, while, ciprofloxacin treatments in both concentrations (0.1 g/L and 0.5 g/L) led to significantly decreased colonization rates. The gene copy number bla OXA-162 correlated with K. pneumoniae in vivo, while a major elevation was observed in the copy number of bla CTX-M-15 from the first day to the fifteenth day in the 0.5 g/L dose ceftazidime treatment group. Our results demonstrate that commonly used antibiotics may have diverse impacts on the colonization rates of intestinally-carried CPE, in addition to affecting the gene copy number of their resistance genes, thus facilitating their stable persistance and dissemination.Balázs SterczFerenc B. FarkasÁkos TóthMárió GajdácsJudit DomokosViola HorváthEszter OstorháziNóra MakraBéla KocsisJános JuhászBalázs LigetiSándor PongorDóra SzabóNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Balázs Stercz Ferenc B. Farkas Ákos Tóth Márió Gajdács Judit Domokos Viola Horváth Eszter Ostorházi Nóra Makra Béla Kocsis János Juhász Balázs Ligeti Sándor Pongor Dóra Szabó The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
description	Abstract Great efforts have been made to limit the transmission of carbapenemase-producing Enterobacteriaceae (CPE), however, the intestinal reservoir of these strains and its modulation by various antibiotics remain largely unexplored. Our aim was to assess the effects of antibiotic administration (ampicillin, ceftazidime, ciprofloxacin) on the establishment and elimination of intestinal colonization with a CTX-M-15 ESBL and OXA-162 carbapenemase producing Klebsiella pneumoniae ST15 (KP5825) in a murine (C57BL/6 male mice) model. Whole genome sequencing of KP5825 strain was performed on an Illumina MiSeq platform. Conjugation assays were carried out by broth mating method. In colonization experiments, 5 × 106 CFU of KP5825 was administered to the animals by orogastric gavage, and antibiotics were administered in their drinking water for two weeks and were changed every day. The gut colonization rates with KP5825 were assessed by cultivation and qPCR. In each of the stool samples, the gene copy number of bla OXA-162 and bla CTX-M-15 were determined by qPCR. Antibiotic concentrations in the stool were determined by high pressure liquid chromatography and a bioanalytical method. The KP5825 contained four different plasmid replicon types, namely IncFII(K), IncL, IncFIB and ColpVC. IncL (containing the bla OXA-162 resistance gene within a Tn1991.2 genetic element) and IncFII(K) (containing the bla CTX-M-15 resistance gene) plasmids were successfully conjugated. During ampicillin and ceftazidime treatments, colonization rate of KP5825 increased, while, ciprofloxacin treatments in both concentrations (0.1 g/L and 0.5 g/L) led to significantly decreased colonization rates. The gene copy number bla OXA-162 correlated with K. pneumoniae in vivo, while a major elevation was observed in the copy number of bla CTX-M-15 from the first day to the fifteenth day in the 0.5 g/L dose ceftazidime treatment group. Our results demonstrate that commonly used antibiotics may have diverse impacts on the colonization rates of intestinally-carried CPE, in addition to affecting the gene copy number of their resistance genes, thus facilitating their stable persistance and dissemination.
format	article
author	Balázs Stercz Ferenc B. Farkas Ákos Tóth Márió Gajdács Judit Domokos Viola Horváth Eszter Ostorházi Nóra Makra Béla Kocsis János Juhász Balázs Ligeti Sándor Pongor Dóra Szabó
author_facet	Balázs Stercz Ferenc B. Farkas Ákos Tóth Márió Gajdács Judit Domokos Viola Horváth Eszter Ostorházi Nóra Makra Béla Kocsis János Juhász Balázs Ligeti Sándor Pongor Dóra Szabó
author_sort	Balázs Stercz
title	The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
title_short	The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
title_full	The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
title_fullStr	The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
title_full_unstemmed	The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15
title_sort	influence of antibiotics on transitory resistome during gut colonization with ctx-m-15 and oxa-162 producing klebsiella pneumoniae st15
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3fd347bee6b843aeb47422a2bdcfe09c
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The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15

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