scholarly journals New insight into bacterial iron competition: A-to-I editing in ferric enterobactin uptake

2020 ◽  
Author(s):  
Wenhan Nie ◽  
Sai Wang ◽  
Qin Xu ◽  
Peihong Wang ◽  
Yan Wu ◽  
...  
Keyword(s):  
Rna Editing ◽  
Pathogenic Bacteria ◽  
Iron Concentration ◽  
3D Structure ◽  
Essential Element ◽  
Iron Starvation ◽  
Editing Event ◽  
Signaling Mechanism ◽  
Growth And Survival ◽  
Chemotaxis Proteins

ABSTRACTIron is an essential element for growth and survival of pathogenic bacteria. However, how these bacteria sense and respond to iron starvation or excess is still not fully understood. Here, we show that xfeA (a homolog of fepA) in Xanthomonas oryzae, can sense the extra-cytoplasmic iron concentration and change the 3D structure of ligand channel domain by A-to-I RNA editing. The percentage of A-to-I RNA editing was increased to 76.87% under iron-starvation, facilitating iron to pass through the XfeA channel without any interference to the strongest Iron(III)–siderophore [Fe-(Ent)]3−. However, under high iron concentration, the percentage of A-to-I editing to xfeA was reduced, thereby restricting the Fe-Ent to pass iron through the channel of XfeA. The variations in concentration of Fe-Ent was sensed by methyl-accepting chemotaxis proteins (MCPs) at cytoplasmic membrane, which influences the expression of a number of chemotaxis related genes. This regulation drives the bacteria to move further towards the iron-rich direction. Overall, our results revealed a new signaling mechanism that bacterial iron sense and homeostasis are modulated through A-to-I RNA editing.IMPORTANCEA-to-I RNA editing, which is catalyzed by the adenosine deaminase, acts on RNA family of enzymes, is one of the most prevalent type of post-transcriptional modification in metazoans. However, the research of A-to-I editing in bacteria is limited and the importance of this editing is still underestimated. In this study, we found that bacteria may use A-to-I editing (xfeA, a homolog of fepA) as an alternative strategy in iron metabolic uptake, as the editing event level can precisely regulate the RNA and the protein sequence within relatively short physiological time scales comparing with the traditional switch “on” and “off” regulation. To best of our knowledge, it is a new identified inching-switch-like mechanism by which pathogens may absorb iron better in order to compete with the hosts.

scholarly journals Growth Phase-Dependent Response of Helicobacter pylori to Iron Starvation

2003 ◽  
Vol 71 (11) ◽  
pp. 6510-6525 ◽  
Author(s):  
D. Scott Merrell ◽  
Lucinda J. Thompson ◽  
Charles C. Kim ◽  
Hazel Mitchell ◽  
Lucy S. Tompkins ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Stationary Phase ◽  
Growth Phase ◽  
Pathogenic Bacteria ◽  
Iron Concentration ◽  
Virulence Gene ◽  
Bioinformatic Analysis ◽  
Iron Starvation ◽  
Direct Role ◽  
Virulence Gene Expression

ABSTRACT Iron is an essential nutrient that is often found in extremely limited available quantities within eukaryotic hosts. Because of this, many pathogenic bacteria have developed regulated networks of genes important for iron uptake and storage. In addition, it has been shown that many bacteria use available iron concentrations as a signal to regulate virulence gene expression. We have utilized DNA microarray technology to identify genes of the human pathogen Helicobacter pylori that are differentially regulated on a growth-inhibiting shift to iron starvation conditions. In addition, the growth phase-dependent expression of these genes was investigated by examining both exponential and stationary growth phase cultures. We identified known iron-regulated genes, as well as a number of genes whose regulation by iron concentration was not previously appreciated. Included in the list of regulated factors were the known virulence genes cagA, vacA, and napA. We examined the effect of iron starvation on the motility of H. pylori and found that exponential- and stationary-phase cultures responded differently to the stress. We further found that while growing cells are rapidly killed by iron starvation, stationary-phase cells show a remarkable ability to survive iron depletion. Finally, bioinformatic analysis of the predicted promoter regions of the differentially regulated genes led to identification of several putative Fur boxes, suggesting a direct role for Fur in iron-dependent regulation of these genes.

scholarly journals Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance

2016 ◽  
Vol 198 (7) ◽  
pp. 1087-1100 ◽  
Author(s):  
Gursonika Binepal ◽  
Kamal Gill ◽  
Paula Crowley ◽  
Martha Cordova ◽  
L. Jeannine Brady ◽  
...  
Keyword(s):  
Stress Tolerance ◽  
Streptococcus Mutans ◽  
Transport System ◽  
Biofilm Formation ◽  
Cellular Response ◽  
Pathogenic Bacteria ◽  
Transport Systems ◽  
Content Type ◽  
Growth And Survival ◽  
Dental Biofilm

ABSTRACTPotassium (K+) is the most abundant cation in the fluids of dental biofilm. The biochemical and biophysical functions of K+and a variety of K+transport systems have been studied for most pathogenic bacteria but not for oral pathogens. In this study, we establish the modes of K+acquisition inStreptococcus mutansand the importance of K+homeostasis for its virulence attributes. TheS. mutansgenome harbors four putative K+transport systems that included two Trk-like transporters (designated Trk1 and Trk2), one glutamate/K+cotransporter (GlnQHMP), and a channel-like K+transport system (Kch). Mutants lacking Trk2 had significantly impaired growth, acidogenicity, aciduricity, and biofilm formation. [K+] less than 5 mM eliminated biofilm formation inS. mutans. The functionality of the Trk2 system was confirmed by complementing anEscherichia coliTK2420 mutant strain, which resulted in significant K+accumulation, improved growth, and survival under stress. Taken together, these results suggest that Trk2 is the main facet of the K+-dependent cellular response ofS. mutansto environment stresses.IMPORTANCEBiofilm formation and stress tolerance are important virulence properties of caries-causingStreptococcus mutans. To limit these properties of this bacterium, it is imperative to understand its survival mechanisms. Potassium is the most abundant cation in dental plaque, the natural environment ofS. mutans. K+is known to function in stress tolerance, and bacteria have specialized mechanisms for its uptake. However, there are no reports to identify or characterize specific K+transporters inS. mutans. We identified the most important system for K+homeostasis and its role in the biofilm formation, stress tolerance, and growth. We also show the requirement of environmental K+for the activity of biofilm-forming enzymes, which explains why such high levels of K+would favor biofilm formation.

scholarly journals Positive Regulation of fur Gene Expression via Direct Interaction of Fur in a Pathogenic Bacterium, Vibrio vulnificus

2007 ◽  
Vol 189 (7) ◽  
pp. 2629-2636 ◽  
Author(s):  
Hyun-Jung Lee ◽  
So Hyun Bang ◽  
Kyu-Ho Lee ◽  
Soon-Jung Park
Keyword(s):  
Gene Expression ◽  
Pathogenic Bacteria ◽  
Vibrio Vulnificus ◽  
Iron Concentration ◽  
Direct Interaction ◽  
Repeated Sequence ◽  
Upstream Region ◽  
Fur Protein

ABSTRACT In pathogenic bacteria, the ability to acquire iron, which is mainly regulated by the ferric uptake regulator (Fur), is essential to maintain growth as well as its virulence. In Vibrio vulnificus, a human pathogen causing gastroenteritis and septicemia, fur gene expression is positively regulated by Fur when the iron concentration is limited (H.-J. Lee et al., J. Bacteriol. 185:5891-5896, 2003). Footprinting analysis revealed that an upstream region of the fur gene was protected by the Fur protein from DNase I under iron-depleted conditions. The protected region, from −142 to −106 relative to the transcription start site of the fur gene, contains distinct AT-rich repeats. Mutagenesis of this repeated sequence resulted in abolishment of binding by Fur. To confirm the role of this cis-acting element in Fur-mediated control of its own gene in vivo, fur expression was monitored in V. vulnificus strains using a transcriptional fusion containing the mutagenized Fur-binding site (fur mt::luxAB). Expression of fur mt::luxAB showed that it was not regulated by Fur and was not influenced by iron concentration. Therefore, this study demonstrates that V. vulnificus Fur acts as a positive regulator under iron-limited conditions by direct interaction with the fur upstream region.

CYB561A3 is the Key Lysosomal Iron Reductase Required for Burkitt B-cell Growth and Survival

Blood ◽  
2021 ◽  
Author(s):  
Zhonghao Wang ◽  
Rui Guo ◽  
Stephen J Trudeau ◽  
Emma Wolinsky ◽  
Tsliil Ast ◽  
...  
Keyword(s):  
B Cell ◽  
Burkitt Lymphoma ◽  
Sub Saharan Africa ◽  
Cell Physiology ◽  
Iron Starvation ◽  
Growth And Survival ◽  
Ferrous Citrate ◽  
Barr Virus ◽  
Epstein Barr ◽  
Sub Saharan

Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma, the leading childhood cancer in sub-Saharan Africa. Burkitt cells retain aspects of germinal center B-cell physiology with MYC-driven B-cell hyperproliferation, yet little is presently known about their iron metabolism. CRISPR/Cas9 analysis highlighted the little studied ferrireductase CYB561A3 as critical for Burkitt proliferation, but not for that of closely related EBV-transformed lymphoblastoid cells or nearly all other Cancer Dependency Map cell lines. Burkitt CYB561A3 knockout induced profound iron starvation, despite ferritinophagy and plasma membrane transferrin upregulation. Elevated concentrations of ascorbic acid, a key CYB561 family electron donor or the labile iron source ferrous citrate rescued Burkitt CYB561A3 deficiency. CYB561A3 knockout caused catastrophic lysosomal and mitochondrial damage and impaired mitochondrial respiration. By contrast, lymphoblastoid B-cells with the transforming EBV latency III program were instead dependent on the STEAP3 ferrireductase. These results highlight CYB561A3 it as an attractive therapeutic Burkitt lymphoma target.

Effects of probiotics-encapsulated live feed on growth and survival of juvenile Clarias batrachus (Linnaeus, 1758) after differential exposure to pathogenic bacteria

2018 ◽  
Vol 16 (1) ◽  
pp. 105-113 ◽  
Author(s):  
A Dey ◽  
K Ghosh ◽  
N Hazra
Keyword(s):  
Pathogenic Bacteria ◽  
Experimental Period ◽  
Clarias Batrachus ◽  
Control Group ◽  
Continuous Exposure ◽  
Protective Effects ◽  
Growth And Survival ◽  
Treatment Groups ◽  
Live Feed ◽  
Differential Exposure

Growth and survival of Clarias batrachus juveniles (10-day old) fed probiotic Bacillus cereus (KR809412) encapsulated live feed (chironomid larvae) have been evaluated after differential exposure to the pathogenic Aeromonas hydrophila (MTCC 1739). Catfish juveniles were stocked at a density of 30 fish per tank in five experimental groups (T1-T5) along with a control group in triplicate and fed twice @ 5% of body weight day-1 for four weeks. Groups T1 and T2 were fed probiotic-encapsulated (PR) or pathogen-inoculated (PGN) live feed respectively, for initial three weeks. During this period groups T3 (PGN-PR-PR), T4 (PR-PGN-PR), and T5 (PR-PR-PGN) were differentially exposed to the pathogen. Live feed without probiotic and pathogen was offered to the control group throughout the experimental period and all other treatment groups (T1-T5) during the 4th week. Continuous exposure to probiotics in group T1 resulted in significantly higher (P<0.05) specific growth rate (SGR, % d-1) and survivability than other groups, whereas, pathogen exposed and probiotic deprived group (T2) noticed with the lowest SGR and the highest mortality. Among other treatment groups (T3, T4 and T5), group T4 resulted in improved SGR and survivability. The coefficient (r value) of 0.867 along with regression slope suggested a positive correlation (0.01 levels) between RNA: DNA and SGR. The study might suggest protective effects of probiotic B. cereus in pathogen exposed C. batrachus juveniles.SAARC J. Agri., 16(1): 105-113 (2018)

scholarly journals The Iron Deficiency Response of Corynebacterium glutamicum and a Link to Thiamine Biosynthesis

2020 ◽  
Vol 86 (10) ◽  
Author(s):  
Andreas Küberl ◽  
Aliye Mengus-Kaya ◽  
Tino Polen ◽  
Michael Bott
Keyword(s):  
Corynebacterium Glutamicum ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Iron Limitation ◽  
Thiamine Pyrophosphate ◽  
Exponential Growth Phase ◽  
Iron Starvation ◽  
Content Type ◽  
Oxoglutarate Dehydrogenase ◽  
Thiamine Biosynthesis

ABSTRACT The response to iron limitation of the Gram-positive soil bacterium Corynebacterium glutamicum was analyzed with respect to secreted metabolites, the transcriptome, and the proteome. During growth in glucose minimal medium, iron limitation caused a shift from lactate to pyruvate as the major secreted organic acid complemented by l-alanine and 2-oxoglutarate. Transcriptome and proteome analyses revealed that a pronounced iron starvation response governed by the transcriptional regulators DtxR and RipA was detectable in the late, but not in the early, exponential-growth phase. A link between iron starvation and thiamine pyrophosphate (TPP) biosynthesis was uncovered by the strong upregulation of thiC. As phosphomethylpyrimidine synthase (ThiC) contains an iron-sulfur cluster, limiting activities of the TPP-dependent pyruvate–2-oxoglutarate dehydrogenase supercomplex probably cause the excretion of pyruvate and 2-oxoglutarate. In line with this explanation, thiamine supplementation could strongly diminish the secretion of these acids. The upregulation of thiC and other genes involved in thiamine biosynthesis and transport is presumably due to TPP riboswitches present at the 5′ end of the corresponding operons. The results obtained in this study provide new insights into iron homeostasis in C. glutamicum and demonstrate that the metabolic consequences of iron limitation can be due to the iron dependency of coenzyme biosynthesis. IMPORTANCE Iron is an essential element for most organisms but causes problems due to poor solubility under oxic conditions and due to toxicity by catalyzing the formation of reactive oxygen species (ROS). Therefore, bacteria have evolved complex regulatory networks for iron homeostasis aiming at a sufficient iron supply while minimizing ROS formation. In our study, the responses of the actinobacterium Corynebacterium glutamicum to iron limitation were analyzed, resulting in a detailed view on the processes involved in iron homeostasis in this model organism. In particular, we provide evidence that iron limitation causes TPP deficiency, presumably due to insufficient activity of the iron-dependent phosphomethylpyrimidine synthase (ThiC). TPP deficiency was deduced from the upregulation of genes controlled by a TPP riboswitch and secretion of metabolites caused by insufficient activity of the TPP-dependent enzymes pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase. To our knowledge, the link between iron starvation and thiamine synthesis has not been elaborated previously.

Behavior of Escherichia coli O157:H7 on Damaged Leaves of Spinach, Lettuce, Cilantro, and Parsley Stored at Abusive Temperatures

2010 ◽  
Vol 73 (2) ◽  
pp. 212-220 ◽  
Author(s):  
ROWAIDA K. KHALIL ◽  
JOSEPH F. FRANK
Keyword(s):  
Escherichia Coli ◽  
Pathogenic Bacteria ◽  
Leaf Damage ◽  
Escherichia Coli O157 ◽  
Oxidation Reactions ◽  
Leaf Extracts ◽  
Romaine Lettuce ◽  
Growth And Survival ◽  
E Coli ◽  
Additional Information

Recent foodborne illness outbreaks associated with the consumption of leafy green produce indicates a need for additional information on the behavior of pathogenic bacteria on these products. Previous research indicates that pathogen growth and survival is enhanced by leaf damage. The objective of this study was to compare the behavior of Escherichia coli O157:H7 on damaged leaves of baby Romaine lettuce, spinach, cilantro, and parsley stored at three abusive temperatures (8, 12, and 15°C). The damaged portions of leaves were inoculated with approximately 105 CFU E. coli O157:H7 per leaf. The pathogen grew on damaged spinach leaves held for 3 days at 8 and 12°C (P &lt; 0.05), with the population increasing by 1.18 and 2.08 log CFU per leaf, respectively. E. coli O157:H7 did not grow on damaged Romaine leaves at 8 or 12°C, but growth was observed after 8 h of storage at 15°C, with an increase of less than 1.0 log. Growth of E. coli O157:H7 on Romaine lettuce held at 8 or 12°C was enhanced when inocula were suspended in 0.05% ascorbic acid, indicating the possibility of inhibition by oxidation reactions associated with tissue damage. Damaged cilantro and Italian parsley leaves held at 8°C for 4 days did not support the growth of E. coli O157:H7. Behavior of the pathogen in leaf extracts differed from behavior on the damaged tissue. This study provides evidence that the damaged portion of a leafy green is a distinct growth niche that elicits different microbial responses in the various types of leafy greens.

scholarly journals Cytolethal Distending Toxin Subunit B: A Review of Structure–Function Relationship

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 595 ◽  
Author(s):  
Benoît J. Pons ◽  
Julien Vignard ◽  
Gladys Mirey
Keyword(s):  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
3D Structure ◽  
Cytolethal Distending Toxin ◽  
Experimental Systems ◽  
Bacterial Virulence Factor ◽  
Function Relationship ◽  
And Function ◽  
Key Residues ◽  
Cell Cycle Block

The Cytolethal Distending Toxin (CDT) is a bacterial virulence factor produced by several Gram-negative pathogenic bacteria. These bacteria, found in distinct niches, cause diverse infectious diseases and produce CDTs differing in sequence and structure. CDTs have been involved in the pathogenicity of the associated bacteria by promoting persistent infection. At the host-cell level, CDTs cause cell distension, cell cycle block and DNA damage, eventually leading to cell death. All these effects are attributable to the catalytic CdtB subunit, but its exact mode of action is only beginning to be unraveled. Sequence and 3D structure analyses revealed similarities with better characterized proteins, such as nucleases or phosphatases, and it has been hypothesized that CdtB exerts a biochemical activity close to those enzymes. Here, we review the relationships that have been established between CdtB structure and function, particularly by mutation experiments on predicted key residues in different experimental systems. We discuss the relevance of these approaches and underline the importance of further study in the molecular mechanisms of CDT toxicity, particularly in the context of different pathological conditions.

scholarly journals Essential Role of Ferritin Pfr in Helicobacter pylori Iron Metabolism and Gastric Colonization

2002 ◽  
Vol 70 (7) ◽  
pp. 3923-3929 ◽  
Author(s):  
Barbara Waidner ◽  
Stefan Greiner ◽  
Stefan Odenbreit ◽  
Holger Kavermann ◽  
Jyoti Velayudhan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Iron Metabolism ◽  
Essential Element ◽  
Iron Starvation ◽  
Iron Storage ◽  
Gastric Colonization ◽  
H Pylori ◽  
Iron Pool

ABSTRACT The reactivity of the essential element iron necessitates a concerted expression of ferritins, which mediate iron storage in a nonreactive state. Here we have further established the role of the Helicobacter pylori ferritin Pfr in iron metabolism and gastric colonization. Iron stored in Pfr enabled H. pylori to multiply under severe iron starvation and protected the bacteria from acid-amplified iron toxicity, as inactivation of the pfr gene restricted growth of H. pylori under these conditions. The lowered total iron content in the pfr mutant, which is probably caused by decreased iron uptake rates, was also reflected by an increased resistance to superoxide stress. Iron induction of Pfr synthesis was clearly diminished in an H. pylori feoB mutant, which lacked high-affinity ferrous iron transport, confirming that Pfr expression is mediated by changes in the cytoplasmic iron pool and not by extracellular iron. This is well in agreement with the recent discovery that iron induces Pfr synthesis by abolishing Fur-mediated repression of pfr transcription, which was further confirmed here by the observation that iron inhibited the in vitro binding of recombinant H. pylori Fur to the pfr promoter region. The functions of H. pylori Pfr in iron metabolism are essential for survival in the gastric mucosa, as the pfr mutant was unable to colonize in a Mongolian gerbil-based animal model. In summary, the pfr phenotypes observed give new insights into prokaryotic ferritin functions and indicate that iron storage and homeostasis are of extraordinary importance for H. pylori to survive in its hostile natural environment.

scholarly journals A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Pierre Mandin ◽  
Sylvia Chareyre ◽  
Frédéric Barras
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Mutational Analysis ◽  
Essential Gene ◽  
Iron Concentration ◽  
Transcriptional Level ◽  
Iron Starvation ◽  
Control Of Gene Expression ◽  
Regulatory Circuit ◽  
Iron Concentrations

ABSTRACT Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs). Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA) RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability. IMPORTANCE Regulatory small RNAs (sRNAs) have emerged as major actors in the control of gene expression in the last few decades. Relatively little is known about how these regulators interact with classical transcription factors to coordinate genetic responses. We show here how an sRNA, RyhB, and a transcription factor, IscR, regulate expression of an essential gene, erpA , in the bacterium E. coli . ErpA is involved in the biogenesis of Fe-S clusters, an important class of cofactors involved in a plethora of cellular reactions. Interestingly, we show that RyhB and IscR repress expression of erpA under opposite conditions in regard to iron concentration, forming a regulatory circuit called an “incoherent network.” This incoherent network serves to maximize expression of erpA at iron concentrations where it is most needed. Altogether, our study paves the way for a better understanding of mixed regulatory networks composed of RNAs and transcription factors.

Sign in / Sign up

Export Citation Format

Share Document