The Transcriptomic and Bioinformatic Characterizations of Iron Acquisition and Heme Utilization in Avibacterium paragallinarum in Response to Iron-Starvation

Avibacterium paragallinarum is the pathogen of infectious coryza, which is a highly contagious respiratory disease of chickens that brings a potentially serious threat to poultry husbandry. Iron is an important nutrient for bacteria and can be obtained from surroundings such as siderophores and hemophores. To date, the mechanisms of iron acquisition and heme utilization as well as detailed regulation in A. paragallinarum have been poorly understood. In this study, we investigated the transcriptomic profiles in detail and the changes of transcriptomes induced by iron restriction in A. paragallinarum using RNA-seq. Compared with the iron-sufficiency control group, many more differentially expressed genes (DEGs) and cellular functions as well as signaling pathways were verified in the iron-restriction group. Among these DEGs, the majority of genes showed decreased expression and some were found to be uniquely present in the iron-restriction group. With an in-depth study of bioinformatic analyses, we demonstrated the crucial roles of the Hut protein and DUF domain-containing proteins, which were preferentially activated in bacteria following iron restriction and contributed to the iron acquisition and heme utilization. Consequently, RT-qPCR results further verified the iron-related DEGs and were consistent with the RNA-seq data. In addition, several novel sRNAs were present in A. paragallinarum and had potential regulatory roles in iron homeostasis, especially in the regulation of Fic protein to ensure stable expression. This is the first report of the molecular mechanism of iron acquisition and heme utilization in A. paragallinarum from the perspective of transcriptomic profiles. The study will contribute to a better understanding of the transcriptomic response of A. paragallinarum to iron starvation and also provide novel insight into the development of new antigens for potential vaccines against infectious coryza by focusing on these iron-related genes.

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Chlamydia trachomatis YtgA is an iron-binding periplasmic protein induced by iron restriction

Microbiology ◽

10.1099/mic.0.030247-0 ◽

2009 ◽

Vol 155 (9) ◽

pp. 2884-2894 ◽

Cited By ~ 20

Author(s):

J. D. Miller ◽

M. S. Sal ◽

M. Schell ◽

J. D. Whittimore ◽

J. E. Raulston

Keyword(s):

Chlamydia Trachomatis ◽

Iron Acquisition ◽

Periplasmic Protein ◽

Iron Starvation ◽

Sexually Transmitted ◽

Iron Restriction ◽

Abc Transport ◽

Transmission Electron ◽

Biochemical Assays

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that is the causative agent of common sexually transmitted diseases and the leading cause of preventable blindness worldwide. It has been observed that YtgA (CT067) is very immunogenic in patients with chlamydial genital infections. Homology analyses suggested that YtgA is a soluble periplasmic protein and a component of an ATP-binding cassette (ABC) transport system for metals such as iron. Since little is known about iron transport in C. trachomatis, biochemical assays were used to determine the potential role of YtgA in iron acquisition. 59Fe binding and competition studies revealed that YtgA preferentially binds iron over nickel, zinc or manganese. Western blot and densitometry techniques showed that YtgA concentrations specifically increased 3–5-fold in C. trachomatis, when cultured under iron-starvation conditions rather than under general stress conditions, such as exposure to penicillin. Finally, immuno-transmission electron microscopy provided evidence that YtgA is more concentrated in C. trachomatis during iron restriction, supporting a possible role for YtgA as a component of an ABC transporter.

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Transcriptomic Response in Pseudomonas aeruginosa towards Treatment with a Kaempferol Isolated from Melastoma malabathricum Linn Leaves

International Journal of Microbiology ◽

10.1155/2020/6915483 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Mourouge Saadi Alwash ◽

Wan Syaidatul Aqma ◽

Wan Yaacob Ahmad ◽

Nazlina Ibrahim

Keyword(s):

Pseudomonas Aeruginosa ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Opportunistic Infections ◽

Membrane Lipid ◽

Rna Seq ◽

Amino Acid Synthesis ◽

Transcriptomic Response ◽

Melastoma Malabathricum ◽

Expression Of Genes

Pseudomonas aeruginosa is one of the main causes of nosocomial infections and is frequently associated with opportunistic infections among hospitalized patients. Kaempferol-3-O-(2′,6′-di-O-trans-p-coumaroyl)-β-D glucopyranoside (KF) is an antipseudomonal compound isolated from the leaves of the native medicinal plant Melastoma malabathricum. Herein, an RNA-seq transcriptomic approach was employed to study the effect of KF treatment on P. aeruginosa and to elucidate the molecular mechanisms underlying the response to KF at two time points (6 h and 24 h incubation). Quantitative real-time PCR (qRT-PCR) was performed for four genes (uvrD, sodM, fumC1, and rpsL) to assess the reliability of the RNA-seq results. The RNA-seq transcriptomic analysis revealed that KF increases the expression of genes involved in the electron transport chain (NADH-I), resulting in the induction of ATP synthesis. Furthermore, KF also increased the expression of genes associated with ATP-binding cassette transporters, flagella, type III secretion system proteins, and DNA replication and repair, which may further influence nutrient uptake, motility, and growth. The results also revealed that KF decreased the expression of a broad range of virulence factors associated with LPS biosynthesis, iron homeostasis, cytotoxic pigment pyocyanin production, and motility and adhesion that are representative of an acute P. aeruginosa infection profile. In addition, P. aeruginosa pathways for amino acid synthesis and membrane lipid composition were modified to adapt to KF treatment. Overall, the present research provides a detailed view of P. aeruginosa adaptation and behaviour in response to KF and highlights the possible therapeutic approach of using plants to combat P. aeruginosa infections.

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Pathogenesis of Infectious Coryza in Chickens (Gallus gallus) by Avibacterium paragallinarumn Isolate of Bangladesh

The Agriculturists ◽

10.3329/agric.v11i1.15240 ◽

2013 ◽

Vol 11 (1) ◽

pp. 39-46 ◽

Cited By ~ 2

Author(s):

M Ali ◽

MS Hossain ◽

S Akter ◽

MAHNA Khan ◽

MM Hossain

Keyword(s):

Culture Broth ◽

Control Group ◽

Nasal Passage ◽

Nasal Discharge ◽

Post Inoculation ◽

Fatty Change ◽

Infectious Coryza ◽

Avibacterium Paragallinarum ◽

Group A ◽

Group B

An investigation was conducted to isolate and identify the causal agent of infectious coryza (IC) with pathogenesis study by local isolate of Avibacterium paragallinarum in chicks in Bangladesh. One isolate of A. paragallinarum was used to study the experimental pathogenesis. For this, 14 days old 24 chicks were grouped into two (A and B) and each group contained 12 birds. Chicks of group A were inoculated with 1ml of 2 days old nutrient broth and were kept as control group while group B were inoculated with 1 ml of 2 days old culture broth of A. paragallinarum. To study the pathology, 4 birds from each group were sacrificed on day 3, 5 and 7 of post inoculation. Sacrificed birds of group A did not reveal any clinical sign and lesion. Chicks of group B showed mild nasal discharge, conjunctivitis, depression and inability to move. The gross lesions of the chicks of group B included mucous in nasal passage, conjunctivitis, swelling of sinuses and face and congested lungs. The microscopic lesions of the chicks of this group were acanthosis and congested blood vessels of nasal passage, pneumonic lesion of lung, focal hepatitis of liver and fatty change and lipid nodules in macrophages of heart which were progressively prominent on day 7 of bacterial inoculation. A. paragallinarum was reisolated from day 7 of post inoculation (PI) from nasal passage of chicks in which lesions were prominent. The proposed experimental pathogenesis was after intranasal inoculation with A. paragallinarum, rhinitis developed, bacteria entered into blood, reached different organs producing lesions. The lesions which are discussed here (rhinitis in association with focal hepatitis, fatty change in heart with lipid granuloma, progressive pneumonic lesions) are not usually present in adult and young birds. DOI: http://dx.doi.org/10.3329/agric.v11i1.15240 The Agriculturists 2013; 11(1) 39-46

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Gene Expression Profile and Co-Expression Network of Pearl Gentian Grouper under Cold Stress by Integrating Illumina and PacBio Sequences

Animals ◽

10.3390/ani11061745 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1745

Author(s):

Ben-Ben Miao ◽

Su-Fang Niu ◽

Ren-Xie Wu ◽

Zhen-Bang Liang ◽

Bao-Gui Tang ◽

...

Keyword(s):

Gene Expression ◽

Cold Stress ◽

Differential Expression Analysis ◽

Endocrine System ◽

Control Group ◽

Regulation Mechanism ◽

Rna Seq ◽

Cold Tolerant ◽

Stress Signals ◽

Membrane Changes

Pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) is a fish of high commercial value in the aquaculture industry in Asia. However, this hybrid fish is not cold-tolerant, and its molecular regulation mechanism underlying cold stress remains largely elusive. This study thus investigated the liver transcriptomic responses of pearl gentian grouper by comparing the gene expression of cold stress groups (20, 15, 12, and 12 °C for 6 h) with that of control group (25 °C) using PacBio SMRT-Seq and Illumina RNA-Seq technologies. In SMRT-Seq analysis, a total of 11,033 full-length transcripts were generated and used as reference sequences for further RNA-Seq analysis. In RNA-Seq analysis, 3271 differentially expressed genes (DEGs), two low-temperature specific modules (tan and blue modules), and two significantly expressed gene sets (profiles 0 and 19) were screened by differential expression analysis, weighted gene co-expression networks analysis (WGCNA), and short time-series expression miner (STEM), respectively. The intersection of the above analyses further revealed some key genes, such as PCK, ALDOB, FBP, G6pC, CPT1A, PPARα, SOCS3, PPP1CC, CYP2J, HMGCR, CDKN1B, and GADD45Bc. These genes were significantly enriched in carbohydrate metabolism, lipid metabolism, signal transduction, and endocrine system pathways. All these pathways were linked to biological functions relevant to cold adaptation, such as energy metabolism, stress-induced cell membrane changes, and transduction of stress signals. Taken together, our study explores an overall and complex regulation network of the functional genes in the liver of pearl gentian grouper, which could benefit the species in preventing damage caused by cold stress.

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MavN is aLegionella pneumophilavacuole-associated protein required for efficient iron acquisition during intracellular growth

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511389112 ◽

2015 ◽

Vol 112 (37) ◽

pp. E5208-E5217 ◽

Cited By ~ 28

Author(s):

Dervla T. Isaac ◽

Rita K. Laguna ◽

Nicole Valtz ◽

Ralph R. Isberg

Keyword(s):

Legionella Pneumophila ◽

Transmembrane Protein ◽

Iron Acquisition ◽

Broth Culture ◽

Growth Defect ◽

Secretion Systems ◽

Intracellular Growth ◽

Iron Starvation ◽

Macrophage Infection ◽

Intracellular Iron

Iron is essential for the growth and virulence of most intravacuolar pathogens. The mechanisms by which microbes bypass host iron restriction to gain access to this metal across the host vacuolar membrane are poorly characterized. In this work, we identify a unique intracellular iron acquisition strategy used byLegionella pneumophila.The bacterial Icm/Dot (intracellular multiplication/defect in organelle trafficking) type IV secretion system targets the bacterial-derived MavN (more regions allowing vacuolar colocalization N) protein to the surface of theLegionella-containing vacuole where this putative transmembrane protein facilitates intravacuolar iron acquisition. TheΔmavNmutant exhibits a transcriptional iron-starvation signature before its growth is arrested during the very early stages of macrophage infection. This intracellular growth defect is rescued only by the addition of excess exogenous iron to the culture medium and not a variety of other metals. Consistent with MavN being a translocated substrate that plays an exclusive role during intracellular growth, the mutant shows no defect for growth in broth culture, even under severe iron-limiting conditions. Putative iron-binding residues within the MavN protein were identified, and point mutations in these residues resulted in defects specific for intracellular growth that are indistinguishable from the ΔmavNmutant. This model of a bacterial protein inserting into host membranes to mediate iron transport provides a paradigm for how intravacuolar pathogens can use virulence-associated secretion systems to manipulate and acquire host iron.

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Multi-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells

BMC Genomics ◽

10.1186/s12864-021-07451-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Clemens Falker-Gieske ◽

Andrea Mott ◽

Sören Franzenburg ◽

Jens Tetens

Keyword(s):

Gene Expression ◽

Retinoic Acid ◽

Cellular Response ◽

Homo Sapiens ◽

Meta Analysis ◽

Early Response ◽

Rna Seq ◽

Transcriptomic Response ◽

Time Points ◽

Lmh Cells

Abstract Background Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points. Results By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response. Conclusions We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.

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Construction of an lncRNA–mRNA Co-Expression Regulatory Network Mediating Inflammation and Regeneration Following Acute Pancreatitis Injury

10.21203/rs.3.rs-1152574/v1 ◽

2021 ◽

Author(s):

Jing Wang ◽

Tianjie Chen ◽

Xiaohua Zhang ◽

Shulei Zhao

Keyword(s):

Acute Pancreatitis ◽

Mrna Expression ◽

Regulatory Network ◽

Noncoding Rnas ◽

Pancreatic Injury ◽

Control Group ◽

Rna Seq ◽

Damage Repair ◽

Injury And Repair ◽

And Function

Abstract Long noncoding RNAs (lncRNAs) play important roles in the occurrence and development of many diseases and can be used as targets for diagnosis and treatment. However, the expression and function of lncRNAs in the injury and repair of acute pancreatitis (AP) are unclear. To decipher lncRNAs’ regulatory roles in AP, we reanalyzed an RNA-seq dataset of 24 pancreatic tissues, including those of normal control mice (BL), those 7 days after mild AP (D7), and those 14 days after mild AP (D14). The results showed significant differences in lncRNA and mRNA expression of D7/D14 groups compared with the control group. Co-expression analysis showed that differentially expressed (DE) lncRNAs were closely related to immunity- and inflammation-related pathways by trans-regulating mRNA expression. The lncRNA–mRNA network showed that the lncRNAs Dancer, Gmm20488, Terc, Snhg3, and Snhg20 were significantly correlated with AP pathogenesis. WGCNA and cis regulation analysis also showed that AP repair-associated lncRNAs were correlated with extracellular and inflammation-related genes, which affect the repair and regeneration of pancreatic injury after AP. In conclusion, the systemic dysregulation of lncRNAs is strongly involved in remodeling AP’s gene expression regulatory network, and the lncRNA–mRNA expression network could identify targets for AP treatment and damage repair.

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Otitis and meningoencephalitis associated with infectious coryza (Avibacterium paragallinarum) in commercial broiler chickens

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638718792964 ◽

2018 ◽

Vol 30 (5) ◽

pp. 784-788 ◽

Cited By ~ 5

Author(s):

Manuela Crispo ◽

C. Gabriel Sentíes-Cué ◽

George L. Cooper ◽

Grace Mountainspring ◽

Charles Corsiglia ◽

...

Keyword(s):

Broiler Chickens ◽

Animal Health ◽

Clinical Signs ◽

Economic Losses ◽

Laboratory System ◽

Sequencing Analysis ◽

Contributing Factors ◽

Infectious Coryza ◽

Avibacterium Paragallinarum ◽

Commercial Broiler

Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head–like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.

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Genes Essential to Iron Transport in the Cyanobacterium Synechocystis sp. Strain PCC 6803

Journal of Bacteriology ◽

10.1128/jb.183.9.2779-2784.2001 ◽

2001 ◽

Vol 183 (9) ◽

pp. 2779-2784 ◽

Cited By ~ 135

Author(s):

Hirokazu Katoh ◽

Natsu Hagino ◽

Arthur R. Grossman ◽

Teruo Ogawa

Keyword(s):

Iron Uptake ◽

Iron Transport ◽

Ferric Iron ◽

Iron Acquisition ◽

Complete Medium ◽

Iron Starvation ◽

Transporter Family ◽

Genes Encoding ◽

In Cells ◽

Pcc 6803

ABSTRACT Genes encoding polypeptides of an ATP binding cassette (ABC)-type ferric iron transporter that plays a major role in iron acquisition inSynechocystis sp. strain PCC 6803 were identified. These genes are slr1295, slr0513, slr0327, and recently reportedsll1878 (Katoh et al., J. Bacteriol. 182:6523–6524, 2000) and were designated futA1, futA2, futB, andfutC, respectively, for their involvement in ferric iron uptake. Inactivation of these genes individually or futA1and futA2 together greatly reduced the activity of ferric iron uptake in cells grown in complete medium or iron-deprived medium. All the fut genes are expressed in cells grown in complete medium, and expression was enhanced by iron starvation. ThefutA1 and futA2 genes appear to encode periplasmic proteins that play a redundant role in iron binding. The deduced products of futB and futC genes contain nucleotide-binding motifs and belong to the ABC transporter family of inner-membrane-bound and membrane-associated proteins, respectively. These results and sequence similarities among the four genes suggest that the Fut system is related to the Sfu/Fbp family of iron transporters. Inactivation of slr1392, a homologue offeoB in Escherichia coli, greatly reduced the activity of ferrous iron transport. This system is induced by intracellular low iron concentrations that are achieved in cells exposed to iron-free medium or in the fut-less mutants grown in complete medium.

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