Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases

Often dismissed as a commensal, <i>Mycoplasma hominis</i> is an increasingly prominent target of research due to its role in septic arthritis and organ transplant failure in immunosuppressed patients, particularly lung transplantation. As a mollicute, its highly reductive genome and stru...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Martin Sharratt, Kirsty Sands, Edward A. R. Portal, Ian Boostrom, Brian A. Mondeja, Nadia M. Rodríguez, Lucy C. Jones, Owen B. Spiller
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Mycoplasma hominis</i> epidemiology United Kingdom genomics antibiotic resistance genome analysis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2edb7604716b44d0a02ed95ba16e6f08
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2edb7604716b44d0a02ed95ba16e6f08
record_format	dspace
spelling	oai:doaj.org-article:2edb7604716b44d0a02ed95ba16e6f082021-11-25T16:24:21ZDefining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases10.3390/antibiotics101113792079-6382https://doaj.org/article/2edb7604716b44d0a02ed95ba16e6f082021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1379https://doaj.org/toc/2079-6382Often dismissed as a commensal, <i>Mycoplasma hominis</i> is an increasingly prominent target of research due to its role in septic arthritis and organ transplant failure in immunosuppressed patients, particularly lung transplantation. As a mollicute, its highly reductive genome and structure render it refractile to most forms of treatment and growing levels of resistance to the few sources of treatment left, such as fluoroquinolones. We examined antimicrobial susceptibility (AST) to fluoroquinolones on 72 isolates and observed resistance in three (4.1%), with corresponding mutations in the quinolone resistance-determining region (QRDR) of S83L or E87G in <i>gyrA</i> and S81I or E85V in <i>parC</i>. However, there were high levels of polymorphism identified between all isolates outside of the QRDR, indicating caution for a genomics-led approach for resistance screening, particularly as we observed a further two quinolone-susceptible isolates solely containing <i>gyrA</i> mutation S83L. However, both isolates spontaneously developed a second spontaneous E85K <i>parC</i> mutation and resistance following prolonged incubation in 4 mg/L levofloxacin for an extra 24–48 h. Continued AST surveillance and investigation is required to understand how <i>gyrA</i> QRDR mutations predispose <i>M. hominis</i> to rapid spontaneous mutation and fluoroquinolone resistance, absent from other susceptible isolates. The unusually high prevalence of polymorphisms in <i>M. hominis</i> also warrants increased genomics’ surveillance.Martin SharrattKirsty SandsEdward A. R. PortalIan BoostromBrian A. MondejaNadia M. RodríguezLucy C. JonesOwen B. SpillerMDPI AGarticle<i>Mycoplasma hominis</i>epidemiologyUnited Kingdomgenomicsantibiotic resistancegenome analysisTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1379, p 1379 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Mycoplasma hominis</i> epidemiology United Kingdom genomics antibiotic resistance genome analysis Therapeutics. Pharmacology RM1-950
spellingShingle	<i>Mycoplasma hominis</i> epidemiology United Kingdom genomics antibiotic resistance genome analysis Therapeutics. Pharmacology RM1-950 Martin Sharratt Kirsty Sands Edward A. R. Portal Ian Boostrom Brian A. Mondeja Nadia M. Rodríguez Lucy C. Jones Owen B. Spiller Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
description	Often dismissed as a commensal, <i>Mycoplasma hominis</i> is an increasingly prominent target of research due to its role in septic arthritis and organ transplant failure in immunosuppressed patients, particularly lung transplantation. As a mollicute, its highly reductive genome and structure render it refractile to most forms of treatment and growing levels of resistance to the few sources of treatment left, such as fluoroquinolones. We examined antimicrobial susceptibility (AST) to fluoroquinolones on 72 isolates and observed resistance in three (4.1%), with corresponding mutations in the quinolone resistance-determining region (QRDR) of S83L or E87G in <i>gyrA</i> and S81I or E85V in <i>parC</i>. However, there were high levels of polymorphism identified between all isolates outside of the QRDR, indicating caution for a genomics-led approach for resistance screening, particularly as we observed a further two quinolone-susceptible isolates solely containing <i>gyrA</i> mutation S83L. However, both isolates spontaneously developed a second spontaneous E85K <i>parC</i> mutation and resistance following prolonged incubation in 4 mg/L levofloxacin for an extra 24–48 h. Continued AST surveillance and investigation is required to understand how <i>gyrA</i> QRDR mutations predispose <i>M. hominis</i> to rapid spontaneous mutation and fluoroquinolone resistance, absent from other susceptible isolates. The unusually high prevalence of polymorphisms in <i>M. hominis</i> also warrants increased genomics’ surveillance.
format	article
author	Martin Sharratt Kirsty Sands Edward A. R. Portal Ian Boostrom Brian A. Mondeja Nadia M. Rodríguez Lucy C. Jones Owen B. Spiller
author_facet	Martin Sharratt Kirsty Sands Edward A. R. Portal Ian Boostrom Brian A. Mondeja Nadia M. Rodríguez Lucy C. Jones Owen B. Spiller
author_sort	Martin Sharratt
title	Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
title_short	Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
title_full	Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
title_fullStr	Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
title_full_unstemmed	Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases
title_sort	defining fluoroquinolone resistance-mediating mutations from non-resistance polymorphisms in <i>mycoplasma hominis</i> topoisomerases
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2edb7604716b44d0a02ed95ba16e6f08
work_keys_str_mv	AT martinsharratt definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT kirstysands definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT edwardarportal definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT ianboostrom definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT brianamondeja definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT nadiamrodriguez definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT lucycjones definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases AT owenbspiller definingfluoroquinoloneresistancemediatingmutationsfromnonresistancepolymorphismsinimycoplasmahominisitopoisomerases
_version_	1718413190343163904

Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in <i>Mycoplasma hominis</i> Topoisomerases

Ejemplares similares