Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>

ABSTRACT Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in H. influenzae is rare in Europe. In this study, we defined acquired resistance gene loci and ftsI mutations in multidrug-re...

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Autores principales:	Kristin Hegstad, Haima Mylvaganam, Jessin Janice, Ellen Josefsen, Audun Sivertsen, Dagfinn Skaare
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Haemophilus influenzae integrative conjugative element multidrug resistant horizontal gene transfer PBP3 beta-lactam resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/278e8518bfcc496686266cb3645a7d33
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spelling	oai:doaj.org-article:278e8518bfcc496686266cb3645a7d332021-11-15T15:27:53ZRole of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>10.1128/mSphere.00969-192379-5042https://doaj.org/article/278e8518bfcc496686266cb3645a7d332020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00969-19https://doaj.org/toc/2379-5042ABSTRACT Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in H. influenzae is rare in Europe. In this study, we defined acquired resistance gene loci and ftsI mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) H. influenzae strains, intending to understand the mode of spread of antibiotic resistance determinants in this species. Horizontal transfer of mobile genetic elements and transformation with resistance-conferring ftsI alleles were contributory. We found one small plasmid and three novel integrative conjugative elements (ICEs) which carry different combinations of resistance genes. Demonstration of transfer and/or ICE circular forms showed that the ICEs are functional. Two extensively MDR genetically unrelated H. influenzae strains (F and G) from the same geographical region shared an identical novel MDR ICE (Tn6686) harboring blaTEM-1, catA2-like, and tet(B). The first Nordic case of MDR H. influenzae septicemia, strain 0, originating from the same geographical area as these strains, had a similar resistance pattern but contained another ICE [Tn6687 with blaTEM-1, catP and tet(B)] with an overall structure quite similar to that of Tn6686. Comparison of the complete ftsI genes among rPBP3 strains revealed that the entire gene or certain regions of it are identical in genetically unrelated strains, indicating horizontal gene transfer. Our findings illustrate that H. influenzae is capable of acquiring resistance against a wide range of commonly used antibiotics through horizontal gene transfer, in terms of conjugative transfer of ICEs and transformation of chromosomal genes. IMPORTANCE Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. As a threat to treatment, resistance against critically important antibiotics is on the rise in H. influenzae. Identifying mechanisms for horizontal acquisition of resistance genes is important to understand how multidrug resistance develops. The present study explores the antimicrobial resistance genes and their context in beta-lactam-resistant H. influenzae with coresistance to up to four non-beta-lactam groups. The results reveal that this organism is capable of acquiring resistance to a wide range of commonly used antibiotics through conjugative transfer of mobile genetic elements and transformation of chromosomal genes, resulting in mosaic genes with a broader resistance spectrum. Strains with chromosomally mediated resistance to extended-spectrum cephalosporins, co-trimoxazole, and quinolones combined with mobile genetic elements carrying genes mediating resistance to ampicillin, tetracyclines, and chloramphenicol have been reported, and further dissemination of such strains represents a particular concern.Kristin HegstadHaima MylvaganamJessin JaniceEllen JosefsenAudun SivertsenDagfinn SkaareAmerican Society for MicrobiologyarticleHaemophilus influenzaeintegrative conjugative elementmultidrug resistanthorizontal gene transferPBP3beta-lactam resistanceMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Haemophilus influenzae integrative conjugative element multidrug resistant horizontal gene transfer PBP3 beta-lactam resistance Microbiology QR1-502
spellingShingle	Haemophilus influenzae integrative conjugative element multidrug resistant horizontal gene transfer PBP3 beta-lactam resistance Microbiology QR1-502 Kristin Hegstad Haima Mylvaganam Jessin Janice Ellen Josefsen Audun Sivertsen Dagfinn Skaare Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
description	ABSTRACT Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in H. influenzae is rare in Europe. In this study, we defined acquired resistance gene loci and ftsI mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) H. influenzae strains, intending to understand the mode of spread of antibiotic resistance determinants in this species. Horizontal transfer of mobile genetic elements and transformation with resistance-conferring ftsI alleles were contributory. We found one small plasmid and three novel integrative conjugative elements (ICEs) which carry different combinations of resistance genes. Demonstration of transfer and/or ICE circular forms showed that the ICEs are functional. Two extensively MDR genetically unrelated H. influenzae strains (F and G) from the same geographical region shared an identical novel MDR ICE (Tn6686) harboring blaTEM-1, catA2-like, and tet(B). The first Nordic case of MDR H. influenzae septicemia, strain 0, originating from the same geographical area as these strains, had a similar resistance pattern but contained another ICE [Tn6687 with blaTEM-1, catP and tet(B)] with an overall structure quite similar to that of Tn6686. Comparison of the complete ftsI genes among rPBP3 strains revealed that the entire gene or certain regions of it are identical in genetically unrelated strains, indicating horizontal gene transfer. Our findings illustrate that H. influenzae is capable of acquiring resistance against a wide range of commonly used antibiotics through horizontal gene transfer, in terms of conjugative transfer of ICEs and transformation of chromosomal genes. IMPORTANCE Haemophilus influenzae colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. As a threat to treatment, resistance against critically important antibiotics is on the rise in H. influenzae. Identifying mechanisms for horizontal acquisition of resistance genes is important to understand how multidrug resistance develops. The present study explores the antimicrobial resistance genes and their context in beta-lactam-resistant H. influenzae with coresistance to up to four non-beta-lactam groups. The results reveal that this organism is capable of acquiring resistance to a wide range of commonly used antibiotics through conjugative transfer of mobile genetic elements and transformation of chromosomal genes, resulting in mosaic genes with a broader resistance spectrum. Strains with chromosomally mediated resistance to extended-spectrum cephalosporins, co-trimoxazole, and quinolones combined with mobile genetic elements carrying genes mediating resistance to ampicillin, tetracyclines, and chloramphenicol have been reported, and further dissemination of such strains represents a particular concern.
format	article
author	Kristin Hegstad Haima Mylvaganam Jessin Janice Ellen Josefsen Audun Sivertsen Dagfinn Skaare
author_facet	Kristin Hegstad Haima Mylvaganam Jessin Janice Ellen Josefsen Audun Sivertsen Dagfinn Skaare
author_sort	Kristin Hegstad
title	Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_short	Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full	Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_fullStr	Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full_unstemmed	Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_sort	role of horizontal gene transfer in the development of multidrug resistance in <named-content content-type="genus-species">haemophilus influenzae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/278e8518bfcc496686266cb3645a7d33
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Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in <named-content content-type="genus-species">Haemophilus influenzae</named-content>

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