Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

Abstract Background Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial leaf blight, a devastating rice disease. The Xoo-rice interaction, wherein wide ranging host- and pathogen-derived proteins and genes wage molecular arms race, is a research hotspot. Hence, the identification of novel rice-induced Xoo virulence factors and characterization of their roles affecting rice global gene expression profiles will provide an integrated and better understanding of Xoo-rice interactions from the molecular perspective. Results Using comparative proteomics and an in vitro interaction system, we revealed that 5 protein spots from Xoo exhibited significantly different expression patterns (|fold change| > 1.5) at 3, 6, 12 h after susceptible rice leaf extract (RLX) treatment. MALDI-TOF MS analysis and pathogenicity tests showed that 4 host-induced proteins, including phosphohexose mutase, inositol monophosphatase, arginase and septum site-determining protein, affected Xoo virulence. Among them, mutants of two host-induced carbohydrate metabolism enzyme-encoding genes, ΔxanA and Δimp, elicited enhanced defense responses and nearly abolished Xoo virulence in rice. To decipher rice differentially expressed genes (DEGs) associated with xanA and imp, transcriptomic responses of ΔxanA-treated and Δimp-treated susceptible rice were compared to those in rice treated with PXO99A at 1 and 3 dpi. A total of 1521 and 227 DEGs were identified for PXO99A vs Δimp at 1 and 3 dpi, while for PXO99A vs ΔxanA, there were 131 and 106 DEGs, respectively. GO, KEGG and MapMan analyses revealed that the DEGs for PXO99A vs Δimp were mainly involved in photosynthesis, signal transduction, transcription, oxidation-reduction, hydrogen peroxide catabolism, ion transport, phenylpropanoid biosynthesis and metabolism of carbohydrates, lipids, amino acids, secondary metabolites, hormones, and nucleotides, while the DEGs from PXO99A vs ΔxanA were predominantly associated with photosynthesis, signal transduction, oxidation-reduction, phenylpropanoid biosynthesis, cytochrome P450 and metabolism of carbohydrates, lipids, amino acids, secondary metabolites and hormones. Although most pathways were associated with both the Δimp and ΔxanA treatments, the underlying genes were not the same. Conclusion Our study identified two novel host-induced virulence factors XanA and Imp in Xoo, and revealed their roles in global gene expression in susceptible rice. These results provide valuable insights into the molecular mechanisms of pathogen infection strategies and plant immunity.

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Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

Journal of Bacteriology ◽

10.1128/jb.00012-18 ◽

2018 ◽

Vol 200 (8) ◽

Cited By ~ 14

Author(s):

Kevin D. Mlynek ◽

William E. Sause ◽

Derek E. Moormeier ◽

Marat R. Sadykov ◽

Kurt R. Hill ◽

...

Keyword(s):

Gene Expression ◽

Virulence Factors ◽

Virulence Gene ◽

Nutrient Depletion ◽

Global Regulator ◽

Two Component System ◽

Component System ◽

Content Type ◽

Virulence Gene Expression ◽

Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

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Identification of ferrichrome- and ferrioxamine B-mediated iron uptake by Aspergillus fumigatus

Biochemical Journal ◽

10.1042/bcj20160066 ◽

2016 ◽

Vol 473 (9) ◽

pp. 1203-1213 ◽

Cited By ~ 11

Author(s):

Yong-Sung Park ◽

Ju-Yeon Kim ◽

Cheol-Won Yun

Keyword(s):

Gene Expression ◽

Plasma Membrane ◽

Aspergillus Fumigatus ◽

Virulence Factors ◽

Membrane Transporters ◽

Yeast Cells ◽

Double Deletion ◽

Ferrioxamine B ◽

Uptake Activity ◽

Opportunistic Fungal Pathogen

Aspergillus fumigatus is an opportunistic fungal pathogen for immunocompromised patients, and genes involved in siderophore metabolism have been identified as virulence factors. Recently, we identified the membrane transporters sit1 and sit2, which are putative virulence factors of A. fumigatus; sit1 and sit2 are homologous to yeast Sit1, and sit1 and sit2 gene expression was up-regulated after iron depletion. When expressed heterologously in Saccharomyces cerevisiae, sit1 and sit2 were localized to the plasma membrane; sit1 efficiently complemented ferrichrome (FC) and ferrioxamine B (FOB) uptake in yeast cells, whereas sit2 complemented only FC uptake. Deletion of sit1 resulted in a decrease in FOB and FC uptake, and deletion of sit2 resulted in a decrease in FC uptake in A. fumigatus. It is of interest that a sit1 and sit2 double-deletion mutant resulted in a synergistic decrease in FC uptake activity. Both sit1 and sit2 were localized to the plasma membrane in A. fumigatus. The expression levels of the sit1 and sit2 genes were dependent on hapX under low-but not high-iron conditions. Furthermore, mirB, and sidA gene expression was up-regulated and sreA expression down-regulated when sit1 and sit2 were deleted. Although sit1 and sit2 failed to affect mouse survival rate, these genes affected conidial killing activity. Taken together, our results suggest that sit1 and sit2 are siderophore transporters and putative virulence factors localized to the plasma membrane.

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Expression of TNF, IL1B, and iNOS2 in the neural cell after induced by Porphyromonas gingivalis with and without coating antibody anti-Porphyromonas gingivalis

F1000Research ◽

10.12688/f1000research.26749.3 ◽

2021 ◽

Vol 9 ◽

pp. 1499

Author(s):

Endang Winiati Bachtiar ◽

Citra F. Putri ◽

Retno D. Soejoedono ◽

Boy M. Bachtiar

Keyword(s):

Gene Expression ◽

Porphyromonas Gingivalis ◽

Virulence Factors ◽

Neural Cell ◽

Gene Expressions ◽

The Brain

Porphyromonas gingivalis has virulence factors such as gingipain and lipopolysaccharide, causing bacteremia to reach the brain and activate neuroinflammatory release cytokines. This study analyzed the effect of the co-culture of neuron cells with P. gingivalis coated with anti-P. gingivalis antibodies against cytokines produced by neuron cells. The gene expressions of the TNF, IL1B, iNOS2 in neurons was evaluated using RT-qPCR. The results showed that P. gingivalis coated with anti-P. gingivalis antibody before co-culture with neuron cells could decrease the gene expression of TNF, IL1B, and iNOS2 of neuron cells.

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CsrRS Regulates Group B Streptococcus Virulence Gene Expression in Response to Environmental pH: a New Perspective on Vaccine Development

Journal of Bacteriology ◽

10.1128/jb.00370-09 ◽

2009 ◽

Vol 191 (17) ◽

pp. 5387-5397 ◽

Cited By ~ 56

Author(s):

Isabella Santi ◽

Renata Grifantini ◽

Sheng-Mei Jiang ◽

Cecilia Brettoni ◽

Guido Grandi ◽

...

Keyword(s):

Gene Expression ◽

Virulence Factors ◽

Vaccine Development ◽

Ph Regulation ◽

Protective Efficacy ◽

Virulence Gene ◽

Ph Sensing ◽

Group B Streptococci ◽

Virulence Gene Expression ◽

Group B

ABSTRACT To identify factors involved in the response of group B streptococci (GBS) to environmental pH, we performed a comparative global gene expression analysis of GBS at acidic and neutral pHs. We found that the transcription of 317 genes was increased at pH 5.5 relative to that at pH 7.0, while 61 genes were downregulated. The global response to acid stress included the differential expression of genes involved in transport, metabolism, stress response, and virulence. Known vaccine candidates, such as BibA and pilus components, were also regulated by pH. We observed that many of the genes involved in the GBS response to pH are known to be controlled by the CsrRS two-component system. Comparison of the regulon of wild-type strain 2603 V/R with that of a csrRS deletion mutant strain revealed that the pH-dependent regulation of 90% of the downregulated genes and 59.3% of the up-regulated genes in strain 2603 V/R was CsrRS dependent and that many virulence factors were overexpressed at high pH. Beta-hemolysin regulation was abrogated by selective inactivation of csrS, suggesting the implication of the CsrS protein in pH sensing. These results imply that the translocation of GBS from the acidic milieu of the vagina to the neutral pH of the neonatal lung signals the up-regulation of GBS virulence factors and conversion from a colonizing to an invasive phenotype. In addition, the fact that increased exposure of BibA on the bacterial surface at pH 7.0 induced opsonophagocytic killing of GBS in immune serum highlights the importance of pH regulation in the protective efficacy of specific antibodies to surface-exposed GBS proteins.

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Vitamin B6 Is Required for Full Motility and Virulence in Helicobacter pylori

mBio ◽

10.1128/mbio.00112-10 ◽

2010 ◽

Vol 1 (3) ◽

Cited By ~ 25

Author(s):

Alexandra Grubman ◽

Alexandra Phillips ◽

Marie Thibonnier ◽

Maria Kaparakis-Liaskos ◽

Chad Johnson ◽

...

Keyword(s):

Gene Expression ◽

Helicobacter Pylori ◽

Virulence Factors ◽

Bacterial Pathogens ◽

Therapeutic Targets ◽

Vitamin B ◽

Human Pathogens ◽

Chronic Colonization ◽

H Pylori

ABSTRACTDespite recent advances in our understanding of howHelicobacter pyloricauses disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors inH. pylori, we generated low-infectivity variants of a mouse-colonizingH. pyloristrain using the classical technique ofin vitroattenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of theEscherichia colivitamin B6biosynthesis enzymes PdxA and PdxJ. Functional complementation studies withE. coliconfirmedH. pyloriPdxA and PdxJ to bebona fidehomologs of vitamin B6biosynthesis enzymes. Importantly,H. pyloriPdxA was required for optimal growthin vitroand was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B6is necessary for the synthesis of glycosylated flagella and for flagellum-based motility inH. pylori. Thus, for the first time, we identify vitamin B6biosynthesis enzymes as novel virulence factors in bacteria. Interestingly,pdxAandpdxJorthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.IMPORTANCEApproximately half of the world’s population is infected withH. pylori, yet howH. pyloribacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors forH. pylori. These genes encoded enzymes involved in the synthesis of vitamin B6, an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B6biosynthesis in human pathogens. We showed that mutantH. pyloribacteria lacking an enzyme involved inde novovitamin B6biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B6biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.

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Pathogenic Biohacking: Induction, Modulation and Subversion of Host Transcriptional Responses by Listeria monocytogenes

Toxins ◽

10.3390/toxins12050294 ◽

2020 ◽

Vol 12 (5) ◽

pp. 294

Author(s):

Matthew J. G. Eldridge ◽

Pascale Cossart ◽

Mélanie A. Hamon

Keyword(s):

Gene Expression ◽

Listeria Monocytogenes ◽

Virulence Factors ◽

Bacterial Pathogen ◽

Typical Feature ◽

Host Gene ◽

Host Cells ◽

Host Gene Expression ◽

Transcriptional Responses ◽

The Impact

During infection, the foodborne bacterial pathogen Listeria monocytogenes dynamically influences the gene expression profile of host cells. Infection-induced transcriptional changes are a typical feature of the host-response to bacteria and contribute to the activation of protective genes such as inflammatory cytokines. However, by using specialized virulence factors, bacterial pathogens can target signaling pathways, transcription factors, and epigenetic mechanisms to alter host gene expression, thereby reprogramming the response to infection. Therefore, the transcriptional profile that is established in the host is delicately balanced between antibacterial responses and pathogenesis, where any change in host gene expression might significantly influence the outcome of infection. In this review, we discuss the known transcriptional and epigenetic processes that are engaged during Listeria monocytogenes infection, the virulence factors that can remodel them, and the impact these processes have on the outcome of infection.

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Variation in the Group B Streptococcus CsrRS Regulon and Effects on Pathogenicity

Journal of Bacteriology ◽

10.1128/jb.01677-07 ◽

2008 ◽

Vol 190 (6) ◽

pp. 1956-1965 ◽

Cited By ~ 44

Author(s):

Sheng-Mei Jiang ◽

Nadeeza Ishmael ◽

Julie Dunning Hotopp ◽

Manuela Puliti ◽

Luciana Tissi ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Virulence Factors ◽

Group B Streptococcus ◽

Regulatory System ◽

Systemic Infection ◽

Global Gene Expression ◽

Pathogenic Potential ◽

Group B

ABSTRACT CsrRS (or CovRS) is a two-component regulatory system that controls expression of multiple virulence factors in the important human pathogen group B Streptococcus (GBS). We now report global gene expression studies in GBS strains 2603V/R and 515 and their isogenic csrR and csrS mutants. Together with data reported previously for strain NEM316, the results reveal a conserved 39-gene CsrRS regulon. In vitro phosphorylation-dependent binding of recombinant CsrR to promoter regions of both positively and negatively regulated genes suggests that direct binding of CsrR can mediate activation as well as repression of target gene expression. Distinct patterns of gene regulation in csrR versus csrS mutants in strain 2603V/R compared to 515 were associated with different hierarchies of relative virulence of wild-type, csrR, and csrS mutants in murine models of systemic infection and septic arthritis. We conclude that CsrRS regulates a core group of genes including important virulence factors in diverse strains of GBS but also displays marked variability in the repertoire of regulated genes and in the relative effects of CsrS signaling on CsrR-mediated gene regulation. Such variation is likely to play an important role in strain-specific adaptation of GBS to particular host environments and pathogenic potential in susceptible hosts.

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Role of the Histone-Like Nucleoid Structuring Protein in Colonization, Motility, and Bile-Dependent Repression of Virulence Gene Expression in Vibrio cholerae

Infection and Immunity ◽

10.1128/iai.74.5.3060-3064.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 3060-3064 ◽

Cited By ~ 30

Author(s):

Amalendu Ghosh ◽

Kalidas Paul ◽

Rukhsana Chowdhury

Keyword(s):

Gene Expression ◽

Vibrio Cholerae ◽

Virulence Factors ◽

Virulence Gene ◽

Virulence Gene Expression

ABSTRACT Bile-mediated repression of virulence gene expression is relieved in a Vibrio cholerae hns mutant. The mutant also exhibited reduced motility due to lower flrA expression, higher in vivo production of the virulence factors, and lower colonization efficiency. The colonization defect of the mutant was due to low FlrA production.

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Molecules Autoinducer 2 and cjA and Their Impact on Gene Expression in Campylobacter jejuni

Journal of Molecular Microbiology and Biotechnology ◽

10.1159/000495411 ◽

2018 ◽

Vol 28 (5) ◽

pp. 207-215 ◽

Cited By ~ 3

Author(s):

Martin Teren ◽

Hana Turonova Michova ◽

Lucie Vondrakova ◽

Katerina Demnerova

Keyword(s):

Gene Expression ◽

Campylobacter Jejuni ◽

Virulence Factors ◽

Stress Responses ◽

Biofilm Formation ◽

Cell Communication ◽

Homoserine Lactone ◽

Receptor Protein ◽

Characteristic Structure ◽

Food Isolate

Quorum sensing is a widespread form of cell-to-cell communication, which is based on the production of signaling molecules known as autoinducers (AIs). The first group contains highly species-specific N-acyl homoserine lactones (N-AHLs), generally known as AI-1, which are produced by AHL synthase. The second group, possessing the characteristic structure of a furanone ring, are known as AI-2. The enzyme responsible for their production is S-ribosylhomocysteine lyase (LuxS). In Campylobacter jejuni, AI-2 and LuxS play a role in many important processes, including biofilm formation, stress response, motility, expression of virulence factors, and colonization. However, neither the receptor protein nor the exact structure of the AI-2 molecule have been identified to date. Similarly, little is known about the possible existence of AHL-synthase producing AI-1 and its impact on gene expression. Recently, an analogue of homoserine lactone, called cjA, was isolated from a cell-free supernatant of C. jejuni strain 81–176 and from the food isolate c11. The molecule cjA particularly impacted the expression of virulence factors and biofilm formation. This review summarizes the role of AI-2 and cjA in the context of biofilm formation, motility, stress responses, and expression of virulence factors.

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