دورية أكاديمية
أعرض في EDS

The small non-coding RNA B11 regulates multiple facets of Mycobacterium abscessus virulence.

التفاصيل البيبلوغرافية
العنوان: The small non-coding RNA B11 regulates multiple facets of Mycobacterium abscessus virulence.
المؤلفون: Bar-Oz M; Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel., Martini MC; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Alonso MN; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Meir M; Rambam Medical Centre, Haifa, Israel., Lore NI; IRCCS San Raffaele Scientific Institute, Milan, Italy., Miotto P; IRCCS San Raffaele Scientific Institute, Milan, Italy., Riva C; IRCCS San Raffaele Scientific Institute, Milan, Italy., Angala SK; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America., Xiao J; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Masiello CS; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Misiakou MA; Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark., Sun H; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Moy JK; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Jackson M; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America., Johansen HK; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark., Cirillo DM; IRCCS San Raffaele Scientific Institute, Milan, Italy., Shell SS; Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America., Barkan D; Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
المصدر: PLoS pathogens [PLoS Pathog] 2023 Aug 21; Vol. 19 (8), pp. e1011575. Date of Electronic Publication: 2023 Aug 21 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Mycobacterium abscessus*/genetics , RNA, Small Untranslated*/genetics, Virulence/genetics ; Anti-Bacterial Agents
مستخلص: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Bar-Oz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: P01 AI143575 United States AI NIAID NIH HHS; R21 AI156415 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Anti-Bacterial Agents)
0 (RNA, Small Untranslated)
SCR Disease Name: Roberts Syndrome
تواريخ الأحداث: Date Created: 20230821 Date Completed: 20230904 Latest Revision: 20240917
رمز التحديث: 20240917
مُعرف محوري في PubMed: PMC10470900
DOI: 10.1371/journal.ppat.1011575
PMID: 37603560
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1011575