Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.

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Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate

International Journal of Molecular Sciences ◽

10.3390/ijms22020736 ◽

2021 ◽

Vol 22 (2) ◽

pp. 736

Author(s):

Jakub Drzmisek ◽

Daniel Stipl ◽

Denisa Petrackova ◽

Branislav Vecerek ◽

Ana Dienstbier

Keyword(s):

Gene Expression ◽

Bordetella Pertussis ◽

Whooping Cough ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Global Gene Expression ◽

Specific Effects ◽

Genes Encoding ◽

Invasive Infections ◽

First Time

Bacterial pathogens sense specific cues associated with different host niches and integrate these signals to appropriately adjust the global gene expression. Bordetella pertussis is a Gram-negative, strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Though B. pertussis does not cause invasive infections, previous results indicated that this reemerging pathogen responds to blood exposure. Here, omics RNA-seq and LC–MS/MS techniques were applied to determine the blood-responsive regulon of B. pertussis. These analyses revealed that direct contact with blood rewired global gene expression profiles in B. pertussis as the expression of almost 20% of all genes was significantly modulated. However, upon loss of contact with blood, the majority of blood-specific effects vanished, with the exception of several genes encoding the T3SS-secreted substrates. For the first time, the T3SS regulator BtrA was identified in culture supernatants of B. pertussis. Furthermore, proteomic analysis identified BP2259 protein as a novel secreted T3SS substrate, which is required for T3SS functionality. Collectively, presented data indicate that contact with blood represents an important cue for B. pertussis cells.

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Faculty Opinions recommendation of Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1166271.627210 ◽

2009 ◽

Author(s):

Bruce Brew

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Neurocognitive Disorders ◽

Hiv 1

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The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

10.1101/2020.07.15.204107 ◽

2020 ◽

Author(s):

Joanna Houghton ◽

Angela Rodgers ◽

Graham Rose ◽

Kristine B. Arnvig

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Small Rnas ◽

Transcriptional Control ◽

Cold Shock ◽

Control Of Gene Expression ◽

Rna Biology ◽

Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

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THE ROLE OF TRANSCRIPTOMICS: PHYSIOLOGICAL EQUIVALENCE BASED ON GENE EXPRESSION PROFILES

Reviews in Agricultural Science ◽

10.7831/ras.5.21 ◽

2017 ◽

Vol 5 (0) ◽

pp. 21-35 ◽

Cited By ~ 1

Author(s):

Shiori Miura ◽

Takehiro Himaki ◽

Junko Takahashi ◽

Hitoshi Iwahashi

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles

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Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

Diabetologia ◽

10.1007/s00125-014-3481-8 ◽

2015 ◽

Vol 58 (4) ◽

pp. 835-844 ◽

Cited By ~ 3

Author(s):

Wenchao Gao ◽

Yu Zhou ◽

Qingyan Li ◽

Quanbo Zhou ◽

Langping Tan ◽

...

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Pancreatic Ductal Adenocarcinoma ◽

Acute Inflammation ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Global Gene Expression ◽

Ductal Adenocarcinoma

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Gene expression profiles predict the possible regulatory role of OPN-mediated signaling pathways in rat liver regeneration

Gene ◽

10.1016/j.gene.2015.11.008 ◽

2016 ◽

Vol 576 (2) ◽

pp. 782-790 ◽

Cited By ~ 6

Author(s):

Gaiping Wang ◽

Shasha Chen ◽

Congcong Zhao ◽

Xiaofang Li ◽

Ling Zhang ◽

...

Keyword(s):

Gene Expression ◽

Liver Regeneration ◽

Signaling Pathways ◽

Rat Liver ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Regulatory Role ◽

Rat Liver Regeneration

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Overexpression of BRE in Pediatric MLL-Rearranged Acute Myeloid Leukemia Associated with t(9;11)(p22;q23).

Blood ◽

10.1182/blood.v114.22.3471.3471 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3471-3471

Author(s):

Brian Balgobind ◽

C. Michel Zwaan ◽

Susan T.C.J.M. Arentsen-Peters ◽

Dirk Reinhardt ◽

Ursula Creutzig ◽

...

Keyword(s):

Gene Expression ◽

Myeloid Leukemia ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Apoptotic Effect ◽

The Mean ◽

Pediatric Aml ◽

Acute Myeloid

Abstract Abstract 3471 Poster Board III-359 One important cytogenetic subgroup of pediatric acute myeloid leukemia (AML) is characterized by translocations of chromosome 11q23, which accounts for 15 to 20% of all cases with an evaluable chromosome analysis. In most of these cases, the mixed lineage leukemia (MLL) gene is involved. More than 50 fusion translocation partners of the MLL gene have been identified and outcome differs by translocation partner, suggesting differences in the biological background. So far these biological differences have not been unravelled. Therefore, we investigated the gene expression profiles of MLL-rearranged subgroups in pediatric AML in order to discover and identify the role of differentially expressed genes. Affymetrix Human Genome U133 plus 2.0 microarrays were used to generate gene expression profiles of 257 pediatric AML cases, which included 21 pediatric AML cases with t(9;11)(p22;q23) and 33 with other MLL-rearrangements. With these profiles, we were able to identify a specific gene expression signature for t(9;11)(p22;q23) using an empirical Bayes linear regression model (Bioconductor package: Limma). This signature was mainly determined by overexpression of the BRE (brain and reproductive organ-expressed) gene. The mean average VSN normalized expression for BRE in the t(9;11)(p22;q23) subgroup was 3.7-fold higher compared with that in other MLL-rearranged cases (p<0.001). Validation by RQ-PCR confirmed this higher expression in t(9;11)(p22;q23) cases (p<0.001). In addition, we confirmed that overexpression of BRE was predominantly found in t(9;11)(p22;q23) in an independent gene expression profile cohort (Ross et al, Blood 2002). Remarkably, MLL-rearranged cases with a BRE expression higher than the mean expression showed a significant better 3 year disease free survival than MLL-rearranged cases with a lower expression (80±13% vs. 30±10%, p=0.02). Previously, overexpression of BRE has been described in hepatocellular carcinomas (HCC) (Chang et al., Oncogene 2008) and an anti-apoptotic effect was described. We transfected BRE in the monomac-1 cell line, which harbors a t(9;11)(p22;q23). We did not find a proliferative advantage for BRE overexpression using a BrDU-assay nor changes in drug sensitivity, indicating that the anti-apoptotic effect as described for HCC in vivo could not be confirmed in vitro in AML. In conclusion, overexpression of the BRE gene is predominantly involved in pediatric MLL-rearranged AML with t(9;11)(p22;q23). Moreover, high expression of BRE showed a favorable prognosis. We did not find any influence of BRE expression on cell proliferation or apoptosis in vitro. This indicates that further studies involving the role of the MLL-fusion protein on BRE transcription are necessary to unravel the leukemogenic role in pediatric AML. Disclosures No relevant conflicts of interest to declare.

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