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Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion

Rebecca Richards, Richard Haigh, Ben Pascoe Orcid Logo, Samuel Sheppard, F Price, D Jenkins, K Rajakumar, Julie Morrissey

Infection and Immunity

Swansea University Author: Ben Pascoe Orcid Logo

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DOI (Published version): 10.1128/IAI.00255-15

Abstract

Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) are a leading cause of healthcare- and community-associated infections and remain a serious clinical threat. S. aureus bacteraemia is further complicated by the phenomenon of treatment failure and persistence despite confirmed in vitro...

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Published in: Infection and Immunity
Published: 2015
Online Access: http://iai.asm.org/content/early/2015/06/03/IAI.00255-15.abstract
URI: https://cronfa.swan.ac.uk/Record/cronfa20102
first_indexed 2015-06-02T02:05:22Z
last_indexed 2018-02-09T04:56:15Z
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recordtype SURis
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spelling 2015-06-09T09:38:20.9229015 v2 20102 2015-01-29 Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion 4660c0eb7e6bfd796cd749ae713ea558 0000-0001-6376-5121 Ben Pascoe Ben Pascoe true false 2015-01-29 Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) are a leading cause of healthcare- and community-associated infections and remain a serious clinical threat. S. aureus bacteraemia is further complicated by the phenomenon of treatment failure and persistence despite confirmed in vitro susceptibility of the infecting strain to the administered antibiotics. In this study isolates originating from two individual cases of persistent S. aureus bacteraemia (PB) were analysed alongside isolates from three cases of resolved bacteraemia (RB) in order to identify traits exclusively associated with persistence.Persistent isolates from both cases showed the same novel virulence traits which were not exhibited by matching initial isolates or by RB isolates. Interestingly, these persistence-associated characteristics did not include two well-described persistence mechanisms, i.e. the presence of small colony variants (SCV) and/or increased intracellular host cell persistence. When compared to their cognate initial isolates, both sets of persistent isolates displayed growth advantages in nutrient-poor medium and showed increases, as analysed by iTRAQ LC-MS, in SaeRS regulated proteins which are involved in immune evasion, host cell adhesion and stress response systems (Map1/Eap, Emp, Sbi, Csp and Trx). Additionally, the persistent isolates displayed improved glucose mediated biofilm formation, had attenuated virulence using a Galleria mellonella virulence model, showed differential sensitivity to external stressors and had daptomycin non-susceptibility. Whole genome sequence comparisons identified several different gain-of-function (GoF) single nucleotide polymorphisms (SNP) in the mprF gene in the sequential isolates of both cases of S. aureus persistent bacteraemia, suggesting a significant role for MprF function during development of S. aureus persistence. Journal Article Infection and Immunity 8 6 2015 2015-06-08 10.1128/IAI.00255-15 http://iai.asm.org/content/early/2015/06/03/IAI.00255-15.abstract COLLEGE NANME COLLEGE CODE Swansea University 2015-06-09T09:38:20.9229015 2015-01-29T01:11:51.4209883 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Rebecca Richards 1 Richard Haigh 2 Ben Pascoe 0000-0001-6376-5121 3 Samuel Sheppard 4 F Price 5 D Jenkins 6 K Rajakumar 7 Julie Morrissey 8
title Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
spellingShingle Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
Ben Pascoe
title_short Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
title_full Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
title_fullStr Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
title_full_unstemmed Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
title_sort Persistent Staphylococcus aureus isolates from two independent bacteraemia cases display phenotypic traits that increase in vivo bacterial fitness and immune evasion
author_id_str_mv 4660c0eb7e6bfd796cd749ae713ea558
author_id_fullname_str_mv 4660c0eb7e6bfd796cd749ae713ea558_***_Ben Pascoe
author Ben Pascoe
author2 Rebecca Richards
Richard Haigh
Ben Pascoe
Samuel Sheppard
F Price
D Jenkins
K Rajakumar
Julie Morrissey
format Journal article
container_title Infection and Immunity
publishDate 2015
institution Swansea University
doi_str_mv 10.1128/IAI.00255-15
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://iai.asm.org/content/early/2015/06/03/IAI.00255-15.abstract
document_store_str 0
active_str 0
description Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) are a leading cause of healthcare- and community-associated infections and remain a serious clinical threat. S. aureus bacteraemia is further complicated by the phenomenon of treatment failure and persistence despite confirmed in vitro susceptibility of the infecting strain to the administered antibiotics. In this study isolates originating from two individual cases of persistent S. aureus bacteraemia (PB) were analysed alongside isolates from three cases of resolved bacteraemia (RB) in order to identify traits exclusively associated with persistence.Persistent isolates from both cases showed the same novel virulence traits which were not exhibited by matching initial isolates or by RB isolates. Interestingly, these persistence-associated characteristics did not include two well-described persistence mechanisms, i.e. the presence of small colony variants (SCV) and/or increased intracellular host cell persistence. When compared to their cognate initial isolates, both sets of persistent isolates displayed growth advantages in nutrient-poor medium and showed increases, as analysed by iTRAQ LC-MS, in SaeRS regulated proteins which are involved in immune evasion, host cell adhesion and stress response systems (Map1/Eap, Emp, Sbi, Csp and Trx). Additionally, the persistent isolates displayed improved glucose mediated biofilm formation, had attenuated virulence using a Galleria mellonella virulence model, showed differential sensitivity to external stressors and had daptomycin non-susceptibility. Whole genome sequence comparisons identified several different gain-of-function (GoF) single nucleotide polymorphisms (SNP) in the mprF gene in the sequential isolates of both cases of S. aureus persistent bacteraemia, suggesting a significant role for MprF function during development of S. aureus persistence.
published_date 2015-06-08T12:42:35Z
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