Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients

ABSTRACT Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Linda T. Viberg, Derek S. Sarovich, Timothy J. Kidd, James B. Geake, Scott C. Bell, Bart J. Currie, Erin P. Price
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Burkholderia pseudomallei antibiotic resistance cystic fibrosis melioidosis parallelism reductive evolution Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/896cc757cfbf4f31ad9c761264b09b7b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:896cc757cfbf4f31ad9c761264b09b7b
record_format	dspace
spelling	oai:doaj.org-article:896cc757cfbf4f31ad9c761264b09b7b2021-11-15T15:51:00ZWithin-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients10.1128/mBio.00356-172150-7511https://doaj.org/article/896cc757cfbf4f31ad9c761264b09b7b2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00356-17https://doaj.org/toc/2150-7511ABSTRACT Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future. IMPORTANCE Burkholderia pseudomallei, the causative agent of melioidosis, is an environmental opportunistic bacterium that typically infects immunocompromised people and those with certain risk factors such as cystic fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections, for reasons that are not well understood. This report is the first to describe B. pseudomallei evolution within the CF lung during chronic infection. We show that the pathways by which B. pseudomallei adapts to the CF lung are similar to those seen in better-studied CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia complex species. Adaptations include the accumulation of antibiotic resistance, loss of nonessential genes, metabolic alterations, and virulence factor attenuation. Known and novel mechanisms of resistance to three of the five antibiotics used in melioidosis treatment were identified. Similar pathways of evolution in CF pathogens, including B. pseudomallei, provide exciting avenues for more-targeted treatment of chronic, recalcitrant infections.Linda T. VibergDerek S. SarovichTimothy J. KiddJames B. GeakeScott C. BellBart J. CurrieErin P. PriceAmerican Society for MicrobiologyarticleBurkholderia pseudomalleiantibiotic resistancecystic fibrosismelioidosisparallelismreductive evolutionMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Burkholderia pseudomallei antibiotic resistance cystic fibrosis melioidosis parallelism reductive evolution Microbiology QR1-502
spellingShingle	Burkholderia pseudomallei antibiotic resistance cystic fibrosis melioidosis parallelism reductive evolution Microbiology QR1-502 Linda T. Viberg Derek S. Sarovich Timothy J. Kidd James B. Geake Scott C. Bell Bart J. Currie Erin P. Price Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
description	ABSTRACT Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future. IMPORTANCE Burkholderia pseudomallei, the causative agent of melioidosis, is an environmental opportunistic bacterium that typically infects immunocompromised people and those with certain risk factors such as cystic fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections, for reasons that are not well understood. This report is the first to describe B. pseudomallei evolution within the CF lung during chronic infection. We show that the pathways by which B. pseudomallei adapts to the CF lung are similar to those seen in better-studied CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia complex species. Adaptations include the accumulation of antibiotic resistance, loss of nonessential genes, metabolic alterations, and virulence factor attenuation. Known and novel mechanisms of resistance to three of the five antibiotics used in melioidosis treatment were identified. Similar pathways of evolution in CF pathogens, including B. pseudomallei, provide exciting avenues for more-targeted treatment of chronic, recalcitrant infections.
format	article
author	Linda T. Viberg Derek S. Sarovich Timothy J. Kidd James B. Geake Scott C. Bell Bart J. Currie Erin P. Price
author_facet	Linda T. Viberg Derek S. Sarovich Timothy J. Kidd James B. Geake Scott C. Bell Bart J. Currie Erin P. Price
author_sort	Linda T. Viberg
title	Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
title_short	Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
title_full	Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
title_fullStr	Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
title_full_unstemmed	Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients
title_sort	within-host evolution of <italic toggle="yes">burkholderia pseudomallei</italic> during chronic infection of seven australasian cystic fibrosis patients
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/896cc757cfbf4f31ad9c761264b09b7b
work_keys_str_mv	AT lindatviberg withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT derekssarovich withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT timothyjkidd withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT jamesbgeake withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT scottcbell withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT bartjcurrie withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients AT erinpprice withinhostevolutionofitalictoggleyesburkholderiapseudomalleiitalicduringchronicinfectionofsevenaustralasiancysticfibrosispatients
_version_	1718427411018678272

Within-Host Evolution of <italic toggle="yes">Burkholderia pseudomallei</italic> during Chronic Infection of Seven Australasian Cystic Fibrosis Patients

Ejemplares similares