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In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemoly...

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Autores principales: Atto, Brianna, Latham, Roger, Kunde, Dale, Gell, David A, Tristram, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238096/
https://www.ncbi.nlm.nih.gov/pubmed/32218184
http://dx.doi.org/10.3390/pathogens9040243
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author Atto, Brianna
Latham, Roger
Kunde, Dale
Gell, David A
Tristram, Stephen
author_facet Atto, Brianna
Latham, Roger
Kunde, Dale
Gell, David A
Tristram, Stephen
author_sort Atto, Brianna
collection PubMed
description Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible individuals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic.
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spelling pubmed-72380962020-05-28 In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus Atto, Brianna Latham, Roger Kunde, Dale Gell, David A Tristram, Stephen Pathogens Article Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible individuals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic. MDPI 2020-03-25 /pmc/articles/PMC7238096/ /pubmed/32218184 http://dx.doi.org/10.3390/pathogens9040243 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Atto, Brianna
Latham, Roger
Kunde, Dale
Gell, David A
Tristram, Stephen
In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title_full In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title_fullStr In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title_full_unstemmed In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title_short In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus
title_sort in vitro anti-nthi activity of haemophilin-producing strains of haemophilus haemolyticus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238096/
https://www.ncbi.nlm.nih.gov/pubmed/32218184
http://dx.doi.org/10.3390/pathogens9040243
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