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Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections

Pseudomonas aeruginosa is a major cause of nosocomial bloodstream infections. This microorganism secretes two major proteases, alkaline protease A (AprA) and elastase B (LasB). Despite several in vitro studies having demonstrated that both purified proteases cleave a number of components of the immu...

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Autores principales: Mateu-Borrás, Margalida, Zamorano, Laura, González-Alsina, Alex, Sánchez-Diener, Irina, Doménech-Sánchez, Antonio, Oliver, Antonio, Albertí, Sebastián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823171/
https://www.ncbi.nlm.nih.gov/pubmed/35145924
http://dx.doi.org/10.3389/fcimb.2021.816356
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author Mateu-Borrás, Margalida
Zamorano, Laura
González-Alsina, Alex
Sánchez-Diener, Irina
Doménech-Sánchez, Antonio
Oliver, Antonio
Albertí, Sebastián
author_facet Mateu-Borrás, Margalida
Zamorano, Laura
González-Alsina, Alex
Sánchez-Diener, Irina
Doménech-Sánchez, Antonio
Oliver, Antonio
Albertí, Sebastián
author_sort Mateu-Borrás, Margalida
collection PubMed
description Pseudomonas aeruginosa is a major cause of nosocomial bloodstream infections. This microorganism secretes two major proteases, alkaline protease A (AprA) and elastase B (LasB). Despite several in vitro studies having demonstrated that both purified proteases cleave a number of components of the immune system, their contribution to P. aeruginosa bloodstream infections in vivo remains poorly investigated. In this study, we used a set of isogenic mutants deficient in AprA, LasB or both to demonstrate that these exoproteases are sufficient to cleave the complement component C3, either soluble or deposited on the bacteria. Nonetheless, exoprotease-deficient mutants were as virulent as the wild-type strain in a murine model of systemic infection, in Caenorhabditis elegans and in Galleria mellonella. Consistently, the effect of the exoproteases on the opsonization of P. aeruginosa by C3 became evident four hours after the initial interaction of the complement with the microorganism and was not crucial to survival in blood. These results indicate that exoproteases AprA and LasB, although conferring the capacity to cleave C3, are not essential for the virulence of P. aeruginosa bloodstream infections.
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spelling pubmed-88231712022-02-09 Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections Mateu-Borrás, Margalida Zamorano, Laura González-Alsina, Alex Sánchez-Diener, Irina Doménech-Sánchez, Antonio Oliver, Antonio Albertí, Sebastián Front Cell Infect Microbiol Cellular and Infection Microbiology Pseudomonas aeruginosa is a major cause of nosocomial bloodstream infections. This microorganism secretes two major proteases, alkaline protease A (AprA) and elastase B (LasB). Despite several in vitro studies having demonstrated that both purified proteases cleave a number of components of the immune system, their contribution to P. aeruginosa bloodstream infections in vivo remains poorly investigated. In this study, we used a set of isogenic mutants deficient in AprA, LasB or both to demonstrate that these exoproteases are sufficient to cleave the complement component C3, either soluble or deposited on the bacteria. Nonetheless, exoprotease-deficient mutants were as virulent as the wild-type strain in a murine model of systemic infection, in Caenorhabditis elegans and in Galleria mellonella. Consistently, the effect of the exoproteases on the opsonization of P. aeruginosa by C3 became evident four hours after the initial interaction of the complement with the microorganism and was not crucial to survival in blood. These results indicate that exoproteases AprA and LasB, although conferring the capacity to cleave C3, are not essential for the virulence of P. aeruginosa bloodstream infections. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8823171/ /pubmed/35145924 http://dx.doi.org/10.3389/fcimb.2021.816356 Text en Copyright © 2022 Mateu-Borrás, Zamorano, González-Alsina, Sánchez-Diener, Doménech-Sánchez, Oliver and Albertí https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Mateu-Borrás, Margalida
Zamorano, Laura
González-Alsina, Alex
Sánchez-Diener, Irina
Doménech-Sánchez, Antonio
Oliver, Antonio
Albertí, Sebastián
Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title_full Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title_fullStr Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title_full_unstemmed Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title_short Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Pseudomonas aeruginosa Bloodstream Infections
title_sort molecular analysis of the contribution of alkaline protease a and elastase b to the virulence of pseudomonas aeruginosa bloodstream infections
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823171/
https://www.ncbi.nlm.nih.gov/pubmed/35145924
http://dx.doi.org/10.3389/fcimb.2021.816356
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