Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection

Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the airways of cystic fibrosis (CF) patients and undergoes a process of genetic adaptation based on mutagenesis. We evaluated the role of mononucleotide G:C and A:T simple sequence repeats (SSRs) in this adaptive process....

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Autores principales: Moyano, Alejandro J., Feliziani, Sofía, Di Rienzo, Julio Alejandro, Smania, Andrea M.
Formato: article
Lenguaje:Inglés
Publicado: 2022
Materias:
Pseudomonas aeruginosa
Fibrosis quística
Repeticiones de secuencia simple
Acceso en línea:http://hdl.handle.net/11086/23817
https://doi.org/10.1371/journal.pone.0080514
Aporte de:
Repositorio Digital Universitario (UNC) de Universidad Nacional de Córdoba
id I10-R14111086-23817
record_format dspace
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-141
collection Repositorio Digital Universitario (UNC)
language Inglés
topic Pseudomonas aeruginosa
Fibrosis quística
Repeticiones de secuencia simple
spellingShingle Pseudomonas aeruginosa
Fibrosis quística
Repeticiones de secuencia simple
Moyano, Alejandro J.
Feliziani, Sofía
Di Rienzo, Julio Alejandro
Smania, Andrea M.
Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
topic_facet Pseudomonas aeruginosa
Fibrosis quística
Repeticiones de secuencia simple
description Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the airways of cystic fibrosis (CF) patients and undergoes a process of genetic adaptation based on mutagenesis. We evaluated the role of mononucleotide G:C and A:T simple sequence repeats (SSRs) in this adaptive process. An in silico survey of the genome sequences of 7 P. aeruginosa strains showed that mononucleotide G:C SSRs but not A:T SSRs were greatly under-represented in coding regions, suggesting a strong counterselection process for G:C SSRs with lengths .5 bp but not for A:T SSRs. A meta-analysis of published whole genome sequence data for a P. aeruginosa strain from a CF patient with chronic airway infection showed that G:C SSRs but not A:T SSRs were frequently mutated during the infection process through the insertion or deletion of one or more SSR subunits. The mutation tendency of G:C SSRs was length-dependent and increased exponentially as a function of SSR length. When this strain naturally became a stable Mismatch Repair System (MRS)-deficient mutator, the degree of increase of G:C SSRs mutations (5-fold) was much higher than that of other types of mutation (2.2-fold or less). Sequence analysis of several mutated genes reported for two different collections, both containing mutator and non- mutator strains of P. aeruginosa from CF chronic infections, showed that the proportion of G:C SSR mutations was significantly higher in mutators than in non-mutators, whereas no such difference was observed for A:T SSR mutations. Our findings, taken together, provide genome-scale evidences that under a MRS-deficient background, long G:C SSRs are able to stochastically bias mutagenic pathways by making the genes in which they are harbored more prone to mutation. The combination of MRS deficiency and virulence-related genes that contain long G:C SSRs is therefore a matter of concern in P. aeruginosa CF chronic infection.
format article
author Moyano, Alejandro J.
Feliziani, Sofía
Di Rienzo, Julio Alejandro
Smania, Andrea M.
author_facet Moyano, Alejandro J.
Feliziani, Sofía
Di Rienzo, Julio Alejandro
Smania, Andrea M.
author_sort Moyano, Alejandro J.
title Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
title_short Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
title_full Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
title_fullStr Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
title_full_unstemmed Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection
title_sort simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in pseudomonas aeruginosa during chronic lung infection
publishDate 2022
url http://hdl.handle.net/11086/23817
https://doi.org/10.1371/journal.pone.0080514
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