Transcriptomic Response of Listeria monocytogenes to Iron Limitation and fur Mutation

ABSTRACT Iron is required by almost all bacteria, but concentrations above physiological levels are toxic. In bacteria, intracellular iron is regulated mostly by the ferric uptake regulator, Fur, or a similar functional protein. Iron limitation results in the regulation of a number of genes, especially those involved in iron uptake. A subset of these genes is the Fur regulon under the control of Fur. In the present study, we have identified Fur- and iron-regulated genes in Listeria monocytogenes by DNA microarray analysis using a fur mutant and its isogenic parent. To identify genes regulated exclusively in response to iron limitation, the whole-genome transcriptional responses to the iron limitation of a fur mutant and its isogenic parent were compared. Fur-regulated genes were identified by comparing the transcriptional profile of the parent with the transcriptional profile of the isogenic fur mutant. Our studies have identified genes regulated exclusively in response to iron and those that are negatively regulated by Fur. We have identified at least 14 genes that were negatively regulated directly by Fur. Under iron-limited conditions, these genes were upregulated, while the expression of fur was found to be downregulated. To further investigate the regulation of fur in response to iron, an ectopic fur promoter-lacZ transcriptional fusion strain was constructed, and its isogenic fur and perR mutant derivatives were generated in L. monocytogenes 10403S. Analysis of the iron limitation of the perR mutant indicated that the regulation of genes under the negative control of Fur was significantly inhibited. Our results indicate that Fur and PerR proteins negatively regulate fur and that under iron-limited conditions, PerR is required for the negative regulation of genes controlled by Fur.

Download Full-text

Effect of lactic acid bacteria on Listeria monocytogenes infection and innate immunity in rabbits

Czech Journal of Animal Science ◽

10.17221/247/2019-cjas ◽

2020 ◽

Vol 65 (No. 1) ◽

pp. 23-30 ◽

Cited By ~ 2

Author(s):

Heping Zhao ◽

Feike Zhang ◽

Jun Chai ◽

Jianping Wang

Keyword(s):

Lactic Acid ◽

Listeria Monocytogenes ◽

Lactic Acid Bacteria ◽

Positive Control ◽

Negative Control ◽

Listeriolysin O ◽

Serum Iga ◽

Probiotic Lactic Acid Bacteria ◽

Spleen And Lymph Nodes ◽

Proinflammatory Factors

The present study aimed to investigate the effect of probiotic lactic acid bacteria (LAB) addition on Listeria monocytogenes translocation and its toxin listeriolysin O (LLO), proinflammatory factors, immune organ indexes and serum immunoglobulins in farmed rabbits. Five treatments included negative control (NC), positive control (PC) with L. monocytogenes infection and supplemental LAB at 3.0 × 106 (low-LAB, L-LAB), 3.0 × 108 (medium-LAB, M-LAB) and 3.0 × 1010 (high-LAB, H-LAB) CFU/kg of diet, respectively. The LAB was a mixture of equal amounts of Lactobacillus acidophilus (ACCC11073), Lactobacillus plantarum (CICC21863) and Enterococcus faecium (CICC20430). A total of 180 weaned rabbits (negative for L. monocytogenes) were randomly assigned to 5 groups with 6 replicates of 6 rabbits each in response to the 5 treatments. L. monocytogenes infection occurred on the first day of feeding trial and dietary LAB supplementation lasted for 14 days. The results showed that on days 7 and 14 post administration, L. monocytogenes in caecum, liver, spleen and lymph nodes was reduced in M-LAB and H-LAB compared to PC (P < 0.05), and linear and quadratic reducing trends were found in liver on day 7 (P ≤ 0.002). On day 14, mucosa LLO mRNA expression and serum TNFα, IL1β and IFNγ were reduced in the three LAB treatments (P < 0.05), and linear and quadratic trends were found on TNFα and IL1β (P ≤ 0.025); indexes of thymus and spleen, serum IgA and IgG were increased in the LAB treatments (P < 0.05). It is concluded that LAB can be used to alleviate L. monocytogenes infection and to improve the immune function of farmed animals.

Download Full-text

Genotypic diversity of S. mutans in dental biofilm formed in situ under sugar stress exposure

Brazilian Dental Journal ◽

10.1590/s0103-64402007000300002 ◽

2007 ◽

Vol 18 (3) ◽

pp. 185-191 ◽

Cited By ~ 6

Author(s):

Rodrigo Alex Arthur ◽

Cínthia Pereira Machado Tabchoury ◽

Renata de Oliveira Mattos-Graner ◽

Altair A. Del Bel Cury ◽

Adriana Franco Paes Leme ◽

...

Keyword(s):

Genotypic Diversity ◽

Negative Control ◽

Stress Exposure ◽

Chain Reaction ◽

Dental Biofilm ◽

Polymerase Chain ◽

Fermentable Carbohydrates ◽

Almost All ◽

Frequent Exposure

In situ dental biofilm composition under sugar exposure is well known, but sugar effect on the genotypic diversity of S. mutans in dental biofilm has not been explored. This study evaluated S. mutans genotypic diversity in dental biofilm formed in situ under frequent exposure to sucrose and its monosaccharide constituents (glucose and fructose). Saliva of 7 volunteers was collected for isolation of S. mutans and the same volunteers wore intraoral palatal appliances, containing enamel slabs, which were submitted to the following treatments: distilled and deionized water (negative control), 10% glucose + 10% fructose (fermentable carbohydrates) solution or 20% sucrose (fermentable and EPS inductor) solution, 8x/day. After 3, 7 and 14 days, the biofilms were colleted and S. mutans colonies were isolated. Arbitrarily primed polymerase chain reaction (AP-PCR) of S. mutans showed that salivary genotypes were also detected in almost all biofilm samples, independently of the treatment, and seemed to reflect those genotypes present at higher proportion in biofilms. In addition to the salivary genotypes, others were found in biofilms but in lower proportions and were distinct among treatment. The data suggest that the in situ model seems to be useful to evaluate genotypic diversity of S. mutans, but, under the tested conditions, it was not possible to clearly show that specific genotypes were selected in the biofilm due to the stress induced by sucrose metabolism or simple fermentation of its monosaccharides.

Download Full-text

COVID-19 infection and subsequent psychiatric morbidity, sleep problems and fatigue: analysis of an English primary care cohort of 226,521 positive patients

10.1101/2021.06.24.21259463 ◽

2021 ◽

Author(s):

Kathryn M Abel ◽

Matthew J Carr ◽

Darren M Ashcroft ◽

Trudie Chalder ◽

Carolyn A Chew-Graham ◽

...

Keyword(s):

Primary Care ◽

Sleep Problems ◽

Psychiatric Morbidity ◽

Negative Control ◽

Control Analysis ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Models ◽

Self Harm ◽

Primary Hypothesis ◽

Almost All

Objectives The primary hypothesis was that the risk of incident or repeat psychiatric illness, fatigue and sleep problems increased following COVID-19 infection. The analysis plan was pre-registered (https://osf.io/n2k34/). Design Matched cohorts were assembled using a UK primary care registry (the CPRD-Aurum database). Patients were followed-up for up to 10 months, from 1st February 2020 to 9th December 2020. Setting Primary care database of 11,923,499 adults (>16 years). Participants From 232,780 adults with a positive COVID-19 test (after excluding those with <2 years historical data or <1 week follow-up), 86,922 without prior mental illness, 19,020 with anxiety or depression, 1,036 with psychosis, 4,152 with fatigue and 4,539 with sleep problems were matched to up to four controls based on gender, general practice and year of birth. A negative control used patients who tested negative for COVID-19 and patients negative for COVID with an influenza diagnosis. Main Outcomes and Measures Cox proportional hazard models estimated the association between a COVID-19 positive test and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking and BMI. Results After adjusting for observed confounders, there was an association between testing positive for COVID-19 and almost all markers of psychiatric morbidity, fatigue and sleep problems. The adjusted hazard ratio (aHR) for incident psychiatric morbidity was 1.75 (95% CI 1.56-1.96). However, there was a similar risk of incident psychiatric morbidity for those with a negative COVID-19 test (aHR 1.57, 95% CI 1.51-1.63) and a larger increase associated with influenza (aHR 2.97, 95% CI 1.36-6.48). Conclusions There is consistent evidence that COVID-19 infection elevates risk of fatigue and sleep problems, however the results from the negative control analysis suggests that residual confounding may be responsible for at least some of the association between COVID-19 and psychiatric morbidity.

Download Full-text

Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia

10.21203/rs.2.14106/v2 ◽

2019 ◽

Author(s):

Leah J Radeke ◽

Michael Herman

Keyword(s):

Candidate Genes ◽

Differentially Expressed Genes ◽

Stenotrophomonas Maltophilia ◽

Defense Mechanisms ◽

Virulent Strain ◽

Differentially Expressed ◽

Transcriptional Responses ◽

Transcriptomic Response ◽

C Elegans ◽

Realistic Interaction

Abstract Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

Download Full-text

RyhB small RNA modulates the free intracellular iron pool and is essential for normal growth during iron limitation in Escherichia coli

Molecular Microbiology ◽

10.1111/j.1365-2958.2006.05439.x ◽

2006 ◽

Vol 62 (4) ◽

pp. 1181-1190 ◽

Cited By ~ 88

Author(s):

Jean-François Jacques ◽

Soojin Jang ◽

Karine Prévost ◽

Guillaume Desnoyers ◽

Maxime Desmarais ◽

...

Keyword(s):

Escherichia Coli ◽

Small Rna ◽

Normal Growth ◽

Iron Limitation ◽

Intracellular Iron ◽

Iron Pool

Download Full-text

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.

Download Full-text

Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways

Infection and Immunity ◽

10.1128/iai.00077-11 ◽

2011 ◽

Vol 79 (9) ◽

pp. 3596-3606 ◽

Cited By ~ 52

Author(s):

Chris S. Rae ◽

Aimee Geissler ◽

Paul C. Adamson ◽

Daniel A. Portnoy

Keyword(s):

Listeria Monocytogenes ◽

Transcriptional Responses ◽

Gram Positive ◽

Content Type ◽

Growth Defects ◽

Gram Positive Bacteria ◽

Host Cell Death

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

Download Full-text

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.6.1983-1988.2004 ◽

2004 ◽

Vol 48 (6) ◽

pp. 1983-1988 ◽

Cited By ~ 35

Author(s):

Michael V. Bland ◽

Salim Ismail ◽

Jack A. Heinemann ◽

Jacqueline I. Keenan

Keyword(s):

Helicobacter Pylori ◽

Antimicrobial Effect ◽

Iron Limitation ◽

Intracellular Iron ◽

Colloidal Bismuth Subcitrate ◽

Iron Deprivation ◽

Atp Levels ◽

Bismuth Subcitrate ◽

Membrane Changes ◽

H Pylori

ABSTRACT Helicobacter pylori is highly susceptible to bismuth, a heavy metal with antimicrobial activity linked to its effect on bacterial iron uptake. Three strains of H. pylori were analyzed for indicators of iron limitation following exposure to the MIC of colloidal bismuth subcitrate (MICCBS). Similar morphologic and outer membrane changes were observed following growth in iron-limiting medium and at the MICCBS that inhibited the growth of all three strains. These changes, which were also observed for iron-limited bacteria, were alleviated by the addition of iron to the cultures. H. pylori ATP levels, reduced in iron-limiting medium, were below the limits of detection in two of the three strains following exposure to bismuth. The addition of iron partially restored bacterial ATP levels in these two strains, although not to normal concentrations. In contrast, exposure of the same strains to the MICCBS failed to deplete intracellular levels of iron, which were significantly reduced by culturing in iron-limiting medium. Thus, the antimicrobial effect of bismuth and of iron limitation on H. pylori may be similar. However, the respective mechanisms of intracellular action would appear to be mediated by different pathways within the cell.

Download Full-text

Different Transcriptional Responses from Slow and Fast Growth Rate Strains of Listeria monocytogenes Adapted to Low Temperature

Frontiers in Microbiology ◽

10.3389/fmicb.2016.00229 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 12

Author(s):

Ninoska Cordero ◽

Felipe Maza ◽

Helen Navea-Perez ◽

Andrés Aravena ◽

Bárbara Marquez-Fontt ◽

...

Keyword(s):

Growth Rate ◽

Listeria Monocytogenes ◽

Low Temperature ◽

Fast Growth ◽

Transcriptional Responses ◽

Fast Growth Rate

Download Full-text

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches

10.1101/2020.07.20.20155507 ◽

2020 ◽

Cited By ~ 1

Author(s):

Micah T McClain ◽

Florica J Constantine ◽

Ricardo Henao ◽

Yiling Liu ◽

Ephraim L Tsalik ◽

...

Keyword(s):

Peripheral Blood ◽

Host Response ◽

Bacterial Pneumonia ◽

Cell Activation ◽

B Cell Activation ◽

Transcriptional Responses ◽

Transcriptomic Response ◽

Blood Samples ◽

Diagnostic Approaches ◽

Interferon Responses

In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.

Download Full-text