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dc.contributor.author
Bar Oz, Michal
dc.contributor.author
Martini, María Carla
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dc.contributor.author
Alonso, Maria Natalia
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dc.contributor.author
Meir, Michal
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Lore, Nicola Ivan
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Miotto, Paolo
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Riva, Camilla
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Angala, Shiva K.
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Xiao, Junpei
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Masiello, Catherine S.
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Misiakou, Maria Anna
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Sun, Huaming
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Moy, Justin K.
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Jackson, Mary
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Johansen, Helle Krogh
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Cirillo, Daniela Maria
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Shell, Scarlet S
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Barkan, Daniel
dc.date.available
2024-04-24T12:09:19Z
dc.date.issued
2023-08
dc.identifier.citation
Bar Oz, Michal; Martini, María Carla; Alonso, Maria Natalia; Meir, Michal; Lore, Nicola Ivan; et al.; The small non-coding RNA B11 regulates multiple facets of Mycobacterium abscessus virulence; Public Library of Science; Plos Pathogens; 19; 8-2023; 1-32
dc.identifier.issn
1553-7366
dc.identifier.uri
http://hdl.handle.net/11336/233961
dc.description.abstract
Mycobacterium abscessus causes severe disease in patients with cystic fibrosis. Little is known in M. abscessus about the roles of small regulatory RNAs (sRNA) in gene regulation. We show that the sRNA B11 controls gene expression and virulence-associated phenotypes in this pathogen. B11 deletion from the smooth strain ATCC_19977 produced a rough strain, increased pro-inflammatory signaling and virulence in multiple infection models, and increased resistance to antibiotics. Examination of clinical isolate cohorts identified isolates with B11 mutations or reduced expression. We used RNAseq and proteomics to investigate the effects of B11 on gene expression and test the impact of mutations found in clinical isolates. Over 200 genes were differentially expressed in the deletion mutant. Strains with the clinical B11 mutations showed expression trends similar to the deletion mutant, suggesting partial loss of function. Among genes upregulated in the B11 mutant, there was a strong enrichment for genes with B11-complementary sequences in their predicted ribosome binding sites (RBS), consistent with B11 functioning as a negative regulator that represses translation via base-pairing to RBSs. Comparing the proteomes similarly revealed that upregulated proteins were strongly enriched for B11-complementary sequences. Intriguingly, genes upregulated in the absence of B11 included components of the ESX-4 secretion system, critical for M. abscessus virulence. Many of these genes had B11-complementary sequences at their RBSs, which we show is sufficient to mediate repression by B11 through direct binding. Altogether, our data show that B11 acts as a direct negative regulator and mediates (likely indirect) positive regulation with pleiotropic effects on gene expression and clinically important phenotypes in M. abscessus. The presence of hypomorphic B11 mutations in clinical strains is consistent with the idea that lower B11 activity may be advantageous for M. abscessus in some clinical contexts. This is the first report on an sRNA role in M. abscessus.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
MYCOBACTERIUM ABSCESSUS
dc.subject
B11
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SNCRNA
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VIRULENCE
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
The small non-coding RNA B11 regulates multiple facets of Mycobacterium abscessus virulence
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-03-11T11:57:06Z
dc.journal.volume
19
dc.journal.pagination
1-32
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Bar Oz, Michal. The Hebrew University of Jerusalem; Israel
dc.description.fil
Fil: Martini, María Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
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Fil: Alonso, Maria Natalia. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Meir, Michal. The Hebrew University of Jerusalem; Israel
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Fil: Lore, Nicola Ivan. No especifíca;
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Fil: Miotto, Paolo. No especifíca;
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Fil: Riva, Camilla. No especifíca;
dc.description.fil
Fil: Angala, Shiva K.. University of Colorado; Estados Unidos
dc.description.fil
Fil: Xiao, Junpei. Worcester Polytechnic Institute; Estados Unidos
dc.description.fil
Fil: Masiello, Catherine S.. Worcester Polytechnic Institute; Estados Unidos
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Fil: Misiakou, Maria Anna. Universidad de Copenhagen; Dinamarca
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Fil: Sun, Huaming. Worcester Polytechnic Institute; Estados Unidos
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Fil: Moy, Justin K.. Worcester Polytechnic Institute; Estados Unidos
dc.description.fil
Fil: Jackson, Mary. University of Colorado; Estados Unidos
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Fil: Johansen, Helle Krogh. No especifíca;
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Fil: Cirillo, Daniela Maria. No especifíca;
dc.description.fil
Fil: Shell, Scarlet S. Worcester Polytechnic Institute; Estados Unidos
dc.description.fil
Fil: Barkan, Daniel. The Hebrew University of Jerusalem; Israel
dc.journal.title
Plos Pathogens
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.ppat.1011575
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.ppat.1011575
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