scholarly journals PerR-Regulated Manganese Ion Uptake Contributes to Oxidative Stress Defense in an Oral Streptococcus

2014 ◽  
Vol 80 (8) ◽  
pp. 2351-2359 ◽  
Author(s):  
Xinhui Wang ◽  
Huichun Tong ◽  
Xiuzhu Dong
Keyword(s):  
Iron Homeostasis ◽  
Critical Role ◽  
Brain Heart Infusion ◽  
Oral Streptococci ◽  
Content Type ◽  
Manganese Ion ◽  
Gram Positive Bacteria ◽  
Wild Type Phenotype ◽  
Oral Streptococcus ◽  
Antioxidative Stress

ABSTRACTMetal homeostasis plays a critical role in antioxidative stress.Streptococcus oligofermentans, an oral commensal facultative anaerobe lacking catalase activity, produces and tolerates abundant H2O2, whereas Dpr (an Fe2+-chelating protein)-dependent H2O2protection does not confer such high tolerance. Here, we report that inactivation ofperR, a peroxide-responsive repressor that regulates zinc and iron homeostasis in Gram-positive bacteria, increased the survival of H2O2-pulsedS. oligofermentans32-fold and elevated cellular manganese 4.5-fold.perRcomplementation recovered the wild-type phenotype. When grown in 0.1 to 0.25 mM MnCl2,S. oligofermentansincreased survival after H2O2stress 2.5- to 23-fold, and even greater survival was found for theperRmutant, indicating that PerR is involved in Mn2+-mediated H2O2resistance inS. oligofermentans. Mutation ofmntAcould not be obtained in brain heart infusion (BHI) broth (containing ∼0.4 μM Mn2+) unless it was supplemented with ≥2.5 μM MnCl2and caused 82 to 95% reduction of the cellular Mn2+level, whilemntABCoverexpression increased cellular Mn2+2.1- to 4.5-fold. Thus, MntABC was identified as a high-affinity Mn2+transporter inS. oligofermentans. mntAmutation reduced the survival of H2O2-pulsedS. oligofermentans5.7-fold, whilemntABCoverexpression enhanced H2O2-challenged survival 12-fold, indicating that MntABC-mediated Mn2+uptake is pivotal to antioxidative stress inS. oligofermentans. perRmutation or H2O2pulsing upregulatedmntABC, while H2O2-induced upregulation diminished in theperRmutant. This suggests thatperRrepressesmntABCexpression but H2O2can release the suppression. In conclusion, this work demonstrates that PerR regulates manganese homeostasis inS. oligofermentans, which is critical to H2O2stress defenses and may be distributed across all oral streptococci lacking catalase.

scholarly journals Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis

2013 ◽  
Vol 82 (1) ◽  
pp. 333-340 ◽  
Author(s):  
Maroof Husain ◽  
Jessica Jones-Carson ◽  
Lin Liu ◽  
Miryoung Song ◽  
J. Royden Saah ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Nitrosative Stress ◽  
Respiratory Activity ◽  
Aminolevulinic Acid ◽  
Critical Role ◽  
Systemic Infection ◽  
Ferric Uptake Regulator ◽  
Content Type ◽  
Hypoxic Conditions ◽  
Serovar Typhimurium

ABSTRACTHerein we report an important role for the ferric uptake regulator (Fur) in the resistance ofSalmonellaentericaserovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1rmurine model of acute systemic infection. The expression offurprotectedSalmonellagrown under normoxic and hypoxic conditions against the bacteriostatic activity of NO. The hypersusceptibility offur-deficientSalmonellato the cytotoxic actions of NO coincides with a marked repression of respiratory activity and the reduced ability of the bacteria to detoxify NO. AfurmutantSalmonellastrain contained reduced levels of the terminal quinol oxidases of the electron transport chain. Addition of the heme precursor δ-aminolevulinic acid restored the cytochrome content, respiratory activity, NO consumption, and wild-type growth in bacteria undergoing nitrosative stress. The innate antinitrosative defenses regulated by Fur added to the adaptive response associated with the NO-detoxifying activity of the flavohemoprotein Hmp. Our investigations indicate that, in addition to playing a critical role in iron homeostasis, Fur is an important antinitrosative determinant ofSalmonellapathogenesis.

scholarly journals Targeting the HUβ Protein PreventsPorphyromonas gingivalisfrom Entering into Preexisting Biofilms

2018 ◽  
Vol 200 (11) ◽  
pp. e00790-17 ◽  
Author(s):  
Christopher J. Rocco ◽  
Lauren O. Bakaletz ◽  
Steven D. Goodman
Keyword(s):  
Oral Cavity ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
The United States ◽  
Extracellular Dna ◽  
Bacterial Biofilms ◽  
Oral Streptococci ◽  
Content Type ◽  
Oral Streptococcus ◽  
Streptococcal Species

ABSTRACTThe oral cavity is home to a wide variety of bacterial species, both commensal, such as various streptococcal species, and pathogenic, such asPorphyromonas gingivalis, one of the main etiological agents of periodontal disease. Our understanding of how these bacteria ultimately cause disease is highly dependent upon understanding how they coexist and interact with one another in biofilm communities and the mechanisms by which biofilms are formed. Our research has demonstrated that the DNABII family of DNA-binding proteins are important components of the extracellular DNA (eDNA)-dependent matrix of bacterial biofilms and that sequestering these proteins via protein-specific antibodies results in the collapse of the biofilm structure and release of the resident bacteria. While the high degree of similarity among the DNABII family of proteins has allowed antibodies derived against specific DNABII proteins to disrupt biofilms formed by a wide range of bacterial pathogens, the DNABII proteins ofP. gingivalishave proven to be antigenically distinct, allowing us to determine if we can use anti-P. gingivalisHUβ antibodies to specifically target this species for removal from a mixed-species biofilm. Importantly, despite forming homotypic biofilmsin vitro,P. gingivalismust enter preexisting biofilmsin vivoin order to persist within the oral cavity. The data presented here indicate that antibodies derived against theP. gingivalisDNABII protein, HUβ, reduce by half the amount ofP. gingivalisorganisms entering into preexisting biofilm formed by four oral streptococcal species. These results support our efforts to develop methods for preventing and treating periodontal disease.IMPORTANCEPeriodontitis is one of the most prevalent chronic infections, affecting 40 to 50% of the population of the United States. The root cause of periodontitis is the presence of bacterial biofilms within the gingival space, withPorphyromonas gingivalisbeing strongly associated with the development of the disease. Periodontitis also increases the risk of secondary conditions and infections such as atherosclerosis and infective endocarditis caused by oral streptococci. To induce periodontitis,P. gingivalisneeds to incorporate into preformed biofilms, with oral streptococci being important binding partners. Our research demonstrates that targeting DNABII proteins with an antibody disperses oral streptococcus biofilm and preventsP. gingivalisentry into oral streptococcus biofilm. These results suggest potential therapeutic treatments for endocarditis caused by streptococci as well as periodontitis.

scholarly journals The Pseudomonas aeruginosa PrrF Small RNAs Regulate Iron Homeostasis during Acute Murine Lung Infection

2017 ◽  
Vol 85 (5) ◽  
Author(s):  
Alexandria A. Reinhart ◽  
Angela T. Nguyen ◽  
Luke K. Brewer ◽  
Justin Bevere ◽  
Jace W. Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Small Rnas ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Content Type ◽  
The Individual

ABSTRACT Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs (sRNAs), which block the expression of iron-containing proteins under iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal (PQS), a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the prrF genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the prrF1-prrF2 intergenic (IG) sequence (the PrrHIG sequence). Previous studies showed that the prrF locus is required for acute lung infection. However, the individual functions of the PrrF and PrrH sRNAs were not determined. Here, we describe a system for differentiating PrrF and PrrH functions by deleting the PrrHIG sequence [prrF(ΔHIG)]. Our analyses of this construct indicate that the PrrF sRNAs, but not PrrH, are required for acute lung infection by P. aeruginosa. Moreover, we show that the virulence defect of the ΔprrF1-prrF2 mutant is due to decreased bacterial burden during acute lung infection. In vivo analysis of gene expression in lung homogenates shows that PrrF-mediated regulation of genes for iron-containing proteins is disrupted in the ΔprrF1-prrF2 mutant during infection, while the expression of genes that mediate PrrF-regulated PQS production are not affected by prrF deletion in vivo. Combined, these studies demonstrate that regulation of iron utilization plays a critical role in P. aeruginosa's ability to survive during infection.

scholarly journals Macrophage Polarization Alters Postphagocytosis Survivability of the CommensalStreptococcus gordonii

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Andrew J. Croft ◽  
Sarah Metcalfe ◽  
Kiyonobu Honma ◽  
Jason G. Kay
Keyword(s):  
Macrophage Polarization ◽  
Oral Bacteria ◽  
Ros Production ◽  
Systemic Diseases ◽  
Oxygen Species ◽  
Oral Streptococci ◽  
Phagocytic Cells ◽  
Content Type ◽  
Systemic Inflammatory Disease ◽  
Oral Streptococcus

ABSTRACTOral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. UsingStreptococcus gordoniias a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance:S. gordoniiintracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease.

scholarly journals A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Feroze Ganaie ◽  
Jamil S. Saad ◽  
Lesley McGee ◽  
Andries J. van Tonder ◽  
Stephen D. Bentley ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Capsular Polysaccharides ◽  
Oral Streptococci ◽  
Genetic Studies ◽  
Content Type ◽  
Capsule Type ◽  
Oral Streptococcus ◽  
Interspecies Recombination ◽  
Large Repertoire ◽  
Unique Chemical

ABSTRACT Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (cps) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D cps has three large regions syntenic to and highly homologous with cps loci from serotype 6C, serotype 39, and an oral streptococcus strain (S. mitis SK145). The 10D cps region syntenic to SK145 is about 6 kb and has a short gene fragment of wciNα at the 5′ end. The presence of this nonfunctional wciNα fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of cps loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination. IMPORTANCE The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.

scholarly journals The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis

2022 ◽  
Author(s):  
Zewen Wen ◽  
Yuxi Zhao ◽  
Zhengyang Gong ◽  
Yuanyuan Tang ◽  
Yanpeng Xiong ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Natural Product ◽  
Iron Homeostasis ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Ginkgolic Acid ◽  
Wide Range ◽  
Novel Antibiotics

The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity.

scholarly journals Regulation of Virulence by the RevR Response Regulator in Clostridium perfringens

2011 ◽  
Vol 79 (6) ◽  
pp. 2145-2153 ◽  
Author(s):  
Thomas J. Hiscox ◽  
Anjana Chakravorty ◽  
Jocelyn M. Choo ◽  
Kaori Ohtani ◽  
Tohru Shimizu ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Response Regulator ◽  
Hydrolytic Enzymes ◽  
Differentially Expressed ◽  
Wild Type ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
First Response ◽  
Wild Type Phenotype ◽  
Genes Encoding

ABSTRACTClostridium perfringenscauses clostridial myonecrosis or gas gangrene and produces several extracellular hydrolytic enzymes and toxins, many of which are regulated by the VirSR signal transduction system. TherevRgene encodes a putative orphan response regulator that has similarity to the YycF (WalR), VicR, PhoB, and PhoP proteins from other Gram-positive bacteria. RevR appears to be a classical response regulator, with an N-terminal receiver domain and a C-terminal domain with a putative winged helix-turn-helix DNA binding region. To determine its functional role, arevRmutant was constructed by allelic exchange and compared to the wild type by microarray analysis. The results showed that more than 100 genes were differentially expressed in the mutant, including several genes involved in cell wall metabolism. TherevRmutant had an altered cellular morphology; unlike the short rods observed with the wild type, the mutant cells formed long filaments. These changes were reversed upon complementation with a plasmid that carried the wild-typerevRgene. Several genes encoding extracellular hydrolytic enzymes (sialidase, hyaluronidase, and α-clostripain) were differentially expressed in therevRmutant. Quantitative enzyme assays confirmed that these changes led to altered enzyme activity and that complementation restored the wild-type phenotype. Most importantly, therevRmutant was attenuated for virulence in the mouse myonecrosis model compared to the wild type and the complemented strains. These results provide evidence that RevR regulates virulence inC. perfringens; it is the first response regulator other than VirR to be shown to regulate virulence in this important pathogen.

scholarly journals Tailoring a Global Iron Regulon to a Uropathogen

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rajdeep Banerjee ◽  
Erin Weisenhorn ◽  
Kevin J. Schwartz ◽  
Kevin S. Myers ◽  
Jeremy D. Glasner ◽  
...  
Keyword(s):  
Amino Acids ◽  
Urinary Tract ◽  
Amino Acid ◽  
Regulatory Network ◽  
Iron Homeostasis ◽  
Iron Limitation ◽  
Content Type ◽  
E Coli ◽  
General Stress ◽  
K 12

ABSTRACT Pathogenicity islands and plasmids bear genes for pathogenesis of various Escherichia coli pathotypes. Although there is a basic understanding of the contribution of these virulence factors to disease, less is known about variation in regulatory networks in determining disease phenotypes. Here, we dissected a regulatory network directed by the conserved iron homeostasis regulator, ferric uptake regulator (Fur), in uropathogenic E. coli (UPEC) strain CFT073. Comparing anaerobic genome-scale Fur DNA binding with Fur-dependent transcript expression and protein levels of the uropathogen to that of commensal E. coli K-12 strain MG1655 showed that the Fur regulon of the core genome is conserved but also includes genes within the pathogenicity/genetic islands. Unexpectedly, regulons indicative of amino acid limitation and the general stress response were also indirectly activated in the uropathogen fur mutant, suggesting that induction of the Fur regulon increases amino acid demand. Using RpoS levels as a proxy, addition of amino acids mitigated the stress. In addition, iron chelation increased RpoS to the same levels as in the fur mutant. The increased amino acid demand of the fur mutant or iron chelated cells was exacerbated by aerobic conditions, which could be partly explained by the O2-dependent synthesis of the siderophore aerobactin, encoded by an operon within a pathogenicity island. Taken together, these data suggest that in the iron-poor environment of the urinary tract, amino acid availability could play a role in the proliferation of this uropathogen, particularly if there is sufficient O2 to produce aerobactin. IMPORTANCE Host iron restriction is a common mechanism for limiting the growth of pathogens. We compared the regulatory network controlled by Fur in uropathogenic E. coli (UPEC) to that of nonpathogenic E. coli K-12 to uncover strategies that pathogenic bacteria use to overcome iron limitation. Although iron homeostasis functions were regulated by Fur in the uropathogen as expected, a surprising finding was the activation of the stringent and general stress responses in the uropathogen fur mutant, which was rescued by amino acid addition. This coordinated global response could be important in controlling growth and survival under nutrient-limiting conditions and during transitions from the nutrient-rich environment of the lower gastrointestinal (GI) tract to the more restrictive environment of the urinary tract. The coupling of the response of iron limitation to increased demand for amino acids could be a critical attribute that sets UPEC apart from other E. coli pathotypes.

scholarly journals Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

2021 ◽  
Author(s):  
Wen-Dai Bao ◽  
Pei Pang ◽  
Xiao-Ting Zhou ◽  
Fan Hu ◽  
Wan Xiong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Gene Set Enrichment Analysis ◽  
Molecular Characteristics ◽  
Intracellular Iron

AbstractIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

scholarly journals PSIX-18 Laurate and its glycerol monoester, monolaurin, as potential additives to control Listeria monocytogenes and tetracycline resistant Enterococcus faecalis in air-exposed silage

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 414-415
Author(s):  
Yamicela Castillo-Castillo ◽  
Marina Ontiveros ◽  
Eric J Scholljegerdes ◽  
Robin Anderson ◽  
Claudio Arzola-Alvarez ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Enterococcus Faecalis ◽  
Brain Heart Infusion ◽  
Bactericidal Effect ◽  
Complete Elimination ◽  
Gram Positive Bacteria ◽  
Viable Cells ◽  
Colony Forming Units ◽  
Feed Value ◽  
Risk Infection

Abstract Silages can harbor pathogenic and antimicrobial resistant microbes which risk infection of food-producing animals. Livestock producers need effective yet environmentally friendly interventions to preserve the feed value of these fermented materials. Medium chain fatty acids such as laurate and its glycerol monoester, monolaurin, are potent inhibitors of many Gram-positive bacteria and when tested at 5 mg/mL in anaerobic cultures (n = 3/treatment) inoculated with 105 colony forming units (CFU) of Listeria monocytogenes and grown at 37oC in ½ strength Brain Heart infusion broth achieved near complete elimination of viable cells after 6 h compared to a 2.2 ± 0.1 log10 CFU/mL increase observed in controls. Culture of a tetracycline-resistant Enterococcus faecalis with 5 mg laurate/mL likewise achieved near complete elimination of viable cells (5 log10 CFU/mL) by 6 h incubation. The bactericidal effect of 5 mg monolaurin was less against E. faecalis, achieving a decrease of 1.8 ± 0.2 log10 CFU/mL and not decreased further after 24 h. When tested against air-exposed silage, pH 7.53 (4 g), mixed with 4 mL water, 5 mg laurate or monolaurin decreased viability of experimentally-inoculated L. monocytogenes (105 CFU/g silage) more (P < 0.05) than untreated controls after 24 h aerobic incubation (22oC), with viable counts being decreased 6.3 ± 0.1, 5.9 ± 0.8 and 4.5 ± 0.1 log10 CFU/g, respectively. In contrast, viable recovery of the experimentally-inoculated (105 CFU/g) tetracycline-resistant E. faecalis was reduced more (P < 0.05) than controls (decreased 0.7 ± 0.1 log10 CFU/g) after 6 h incubation when similarly tested with laurate and monolaurin (1.7 ± 0.5 and 3.0 ± 0.9 log10 CFU/g, respectively) but counts after 24 h were similar, decreasing on average 2.0 ± 0.5 log10 CFU/g). Results indicate laurate and monolaurin may be useful in killing L. monocytogenes and tetracycline-resistant E. faecalis during silage feed-out.

Sign in / Sign up

Export Citation Format

Share Document