Comparative profiling of the transcriptional response to iron restriction in six serotypes of Actinobacillus pleuropneumoniae with different virulence potential

Klitgaard, Kirstine; Friis, Carsten; Angen, Øystein; Boye, Mette

doi:10.1186/1471-2164-11-698

Cited by 24 publications

(20 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3b), and showed that iron deficit was able to induce the expression of feo and ycl. These results are consistent with previous reports that describe up-regulation of a system related to iron uptake (Baichoo et al 2002;Klitgaard et al 2010) and reveal some of the mechanisms employed by E. faecalis to face changes in iron availability.…”

Section: (Colour Online)]supporting

confidence: 93%

Transcriptomic response of Enterococcus faecalis to iron excess

et al. 2012

View full text Add to dashboard Cite

Iron is an essential nutrient for sustaining bacterial growth; however, little is known about the molecular mechanisms that govern gene expression during the homeostatic response to iron availability. In this study we analyzed the global transcriptional response of Enterococcus faecalis to a non-toxic iron excess in order to identify the set of genes that respond to an increment of intracellular iron. Our results showed an up-regulation of transcriptional regulators of the Fur family (PerR and ZurR), the cation efflux family (CzcD) and ferredoxin, while proton-dependent Mn/Fe (MntH) transporters and the universal stress protein (UspA) were down-regulated. This indicated that E. faecalis was able to activate a transcriptional response while growing in the presence of an excess of non-toxic iron, assuring the maintenance of iron homeostasis. Gene expression analysis of E. faecalis treated with H(2)O(2) indicated that a fraction of the transcriptional changes induced by iron appears to be mediated by oxidative stress. A comparison of our transcriptomic data with a recently reported set of differentially expressed genes in E. faecalis grown in blood, revealed an important fraction of common genes. In particular, genes associated to oxidative stress were up-regulated in both conditions, while genes encoding the iron uptake system (feo and ycl operons) were up-regulated when cells were grown in blood. This suggested that blood cultures mimic an iron deficit, and was corroborated by measuring feo and ycl expression in E. faecalis treated with the iron chelating agent 2,2-dipyridil. In summary, our group identified an adaptive transcriptional mechanism in response to metal ion stress in E. faecalis, providing a foundation for future in-depth functional studies of the iron-activated regulatory network.

show abstract

Section: (Colour Online)]supporting

confidence: 93%

Transcriptomic response of Enterococcus faecalis to iron excess

et al. 2012

View full text Add to dashboard Cite

show abstract

“…This is another argument that confirms the validity of our microarray 363 17 results, as already described in similar works (Allen et al 2010;Klitgaard et al 2010; 364 Vasileva et al 2012). 365…”

Section: Discussion 340supporting

confidence: 90%

“…The range of log 2 fold changes was apparently low, ranging between 357 1.78 and -2.13, but the numbers obtained were in general quite similar to those observed for 358 transcriptomic analyses of iron starvation in other microorganisms (Allen et al 2010; Basler 359 et al 2006;Brickman et al 2011;Klitgaard et al 2010;Madsen et al 2006). However, very 360 interestingly the changes observed in our work were in most cases for genes grouped in 361 operons, and genes belonging to the same operon underwent, as expected, almost identical 362…”

Section: Discussion 340supporting

confidence: 69%

Peer Review #1 of "Multi-omic profiling to assess the effect of iron starvation in Streptococcus pneumoniae TIGR4 (v0.2)"

2018

View full text Add to dashboard Cite

17We applied multi-omics approaches (transcriptomics, proteomics and metabolomics) to study 18 the effect of iron starvation on the Gram-positive human pathogen Streptococcus pneumoniae 19 to elucidate global changes in the bacterium in a condition similar to what can be found in the 20 host during an infectious episode. We treated the reference strain TIGR4 with the iron 21 chelator deferoxamine mesylate. DNA microarrays revealed changes in the expression of 22 operons involved in multiple biological processes, with a prevalence of genes coding for ion 23 binding proteins. We also studied the changes in protein abundance by 2-DE followed by 24 MALDI-TOF/TOF analysis of total cell extracts and secretome fractions. The main proteomic 25 changes were found in proteins related to the primary and amino sugars metabolism, 26 especially in enzymes with divalent cations as cofactors. Finally, the metabolomic analysis of 27 intracellular metabolites showed altered levels of amino sugars involved in the cell wall 28peptidoglycan metabolism. This work shows the utility of multi-perspective studies that can 29 provide complementary results for the comprehension of how a given condition can influence 30 on global physiological changes in microorganisms. 31 32 3 Introduction 33Bacteria need a plethora of factors for optimal growth, being iron an essential micronutrient. 34Within the human body, the free concentration of this element is approximately 10 -18 M (Yang 35 et al. 2014), which is too low to hold a growth capable of supporting bacterial infections. The 36 low concentrations of free iron within the host are due to the scavenging of this element by 37 different high-affinity proteins (e.g. transferrin, lactoferrin, haemoglobin, etc.) (Froehlich et 38 al. 2009). Therefore, in order to survive in the host, pathogens need to develop especial 39 strategies to uptake the minimum amount that they require of such a nutrient (Nanduri et al. 40 2008), as the direct extraction of this metal cation from host iron-containing proteins or by 41 capturing ferric-binding siderophores from host environments via ABC transporters (Ge & 42 Sun 2014). Moreover, the capacity of bacterial pathogens for iron acquisition represents itself 43 an important virulence determinant (Kanaujia et al. 2015). In addition, pathogens can also 44 modify their energetic metabolism to adapt it to the environmental situation within the host. 45Streptococcus pneumoniae, also known as the pneumococcus, is a Gram-positive 46 microorganism that lives as a commensal in the human respiratory tract and that, under 47 appropriate circumstances, becomes pathogenic, being able to cause high morbidity and 48 mortality (Blasi et al. 2012; Olaya-Abril et al. 2014b). This bacterium is a major cause of 49 mucosal diseases such as otitis media and sinusitis, and is a prevalent pathogen in different 50 invasive diseases including pneumonia, bacteremia, meningitis, and sepsis (O'Brien et al. 512009). Pneumococcal pneumonia, which is the major clinical manife...

show abstract

“…pleuropneumoniae genome [ 32 ]. In a recent study, genes encoding a putative enterobactin receptor system and a cirA like siderophore have been identified to be up-regulated under iron-restricted conditions [ 33 , 44 ]. These known and/or putative iron-acquisition systems might have roles in catecholamine-induced growth of A .…”

Section: Discussionmentioning

confidence: 99%

Catecholamines Promote Actinobacillus pleuropneumoniae Growth by Regulating Iron Metabolism

Chen

Bei

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

Catecholamines are host stress hormones that can induce the growth of many bacteria by facilitating iron utilization and/or regulate the expression of virulence genes through specific hormone receptors. Whether these two responsive pathways are interconnected is unknown. In our previous study, it was found that catecholamines can regulate the expression of a great number of genes of Actinobacillus pleuropneumoniae, an important swine respiratory pathogen. However, bacterial growth was not affected by catecholamines in rich medium. In this study, it was discovered that catecholamines affected A. pleuropneumoniae growth in chemically defined medium (CDM). We found that serum inhibited A. pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine promoted A. pleuropneumoniae growth in the CDM containing serum. The known bacterial hormone receptor QseC didn’t play roles in this process. Ion-supplementation and transcriptome analysis indicated that serum addition resulted in iron-restricted conditions which were alleviated by the addition of catecholamines. Transferrin, one of the components in serum, inhibited the growth of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A. pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is independent of the adrenergic receptor QseC.

show abstract

Comparative profiling of the transcriptional response to iron restriction in six serotypes of Actinobacillus pleuropneumoniae with different virulence potential

Cited by 24 publications

References 72 publications

Transcriptomic response of Enterococcus faecalis to iron excess

Transcriptomic response of Enterococcus faecalis to iron excess

Peer Review #1 of "Multi-omic profiling to assess the effect of iron starvation in Streptococcus pneumoniae TIGR4 (v0.2)"

Catecholamines Promote Actinobacillus pleuropneumoniae Growth by Regulating Iron Metabolism

Contact Info

Product

Resources

About