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Steimbrüch BA, Sartorio MG, Cortez N, Albanesi D, Lisa MN, Repizo GD. The distinctive roles played by the superoxide dismutases of the extremophile Acinetobacter sp. Ver3. Sci Rep 2022; 12:4321. [PMID: 35279679 PMCID: PMC8918354 DOI: 10.1038/s41598-022-08052-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/28/2022] [Indexed: 11/09/2022] Open
Abstract
Acinetobacter sp. Ver3 is a polyextremophilic strain characterized by a high tolerance to radiation and pro-oxidants. The Ver3 genome comprises the sodB and sodC genes encoding an iron (AV3SodB) and a copper/zinc superoxide dismutase (AV3SodC), respectively; however, the specific role(s) of these genes has remained elusive. We show that the expression of sodB remained unaltered in different oxidative stress conditions whereas sodC was up-regulated in the presence of blue light. Besides, we studied the changes in the in vitro activity of each SOD enzyme in response to diverse agents and solved the crystal structure of AV3SodB at 1.34 Å, one of the highest resolutions achieved for a SOD. Cell fractionation studies interestingly revealed that AV3SodB is located in the cytosol whereas AV3SodC is also found in the periplasm. Consistently, a bioinformatic analysis of the genomes of 53 Acinetobacter species pointed out the presence of at least one SOD type in each compartment, suggesting that these enzymes are separately required to cope with oxidative stress. Surprisingly, AV3SodC was found in an active state also in outer membrane vesicles, probably exerting a protective role. Overall, our multidisciplinary approach highlights the relevance of SOD enzymes when Acinetobacterspp. are confronted with oxidizing agents.
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Affiliation(s)
- Bruno Alejandro Steimbrüch
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina
| | - Mariana Gabriela Sartorio
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina
| | - Néstor Cortez
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina
| | - Daniela Albanesi
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Ocampo y Esmeralda, S2002LRK, Rosario, Argentina.,Plataforma de Biología Estructural y Metabolómica (PLABEM), Ocampo y Esmeralda, S2002LRK, Rosario, Argentina
| | - María-Natalia Lisa
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Ocampo y Esmeralda, S2002LRK, Rosario, Argentina. .,Plataforma de Biología Estructural y Metabolómica (PLABEM), Ocampo y Esmeralda, S2002LRK, Rosario, Argentina.
| | - Guillermo Daniel Repizo
- Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina.
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Cao H, Xu H, Ning C, Xiang L, Ren Q, Zhang T, Zhang Y, Gao R. Multi-Omics Approach Reveals the Potential Core Vaccine Targets for the Emerging Foodborne Pathogen Campylobacter jejuni. Front Microbiol 2021; 12:665858. [PMID: 34248875 PMCID: PMC8265506 DOI: 10.3389/fmicb.2021.665858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/06/2021] [Indexed: 11/30/2022] Open
Abstract
Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans around the world. The emergence of bacterial resistance is becoming more serious; therefore, development of new vaccines is considered to be an alternative strategy against drug-resistant pathogen. In this study, we investigated the pangenome of 173 C. jejuni strains and analyzed the phylogenesis and the virulence factor genes. In order to acquire a high-quality pangenome, genomic relatedness was firstly performed with average nucleotide identity (ANI) analyses, and an open pangenome of 8,041 gene families was obtained with the correct taxonomy genomes. Subsequently, the virulence property of the core genome was analyzed and 145 core virulence factor (VF) genes were obtained. Upon functional genomics and immunological analyses, five core VF proteins with high antigenicity were selected as potential core vaccine targets for humans. Furthermore, functional annotations indicated that these proteins are involved in important molecular functions and biological processes, such as adhesion, regulation, and secretion. In addition, transcriptome analysis in human cells and pig intestinal loop proved that these vaccine target genes are important in the virulence of C. jejuni in different hosts. Comprehensive pangenome and relevant animal experiments will facilitate discovering the potential core vaccine targets with improved efficiency in reverse vaccinology. Likewise, this study provided some insights into the genetic polymorphism and phylogeny of C. jejuni and discovered potential vaccine candidates for humans. Prospective development of new vaccines using the targets will be an alternative to the use of antibiotics and prevent the development of multidrug-resistant C. jejuni in humans and even other animals.
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Affiliation(s)
- Hengchun Cao
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Hanxiao Xu
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Chunhui Ning
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Li Xiang
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Qiufang Ren
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Tiantian Zhang
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Yusen Zhang
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Rui Gao
- School of Control Science and Engineering, Shandong University, Jinan, China
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Favier A, Gans P, Boeri Erba E, Signor L, Muthukumar SS, Pfannschmidt T, Blanvillain R, Cobessi D. The Plastid-Encoded RNA Polymerase-Associated Protein PAP9 Is a Superoxide Dismutase With Unusual Structural Features. FRONTIERS IN PLANT SCIENCE 2021; 12:668897. [PMID: 34276730 PMCID: PMC8278866 DOI: 10.3389/fpls.2021.668897] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/28/2021] [Indexed: 05/09/2023]
Abstract
In Angiosperms, the plastid-encoded RNA polymerase (PEP) is a multimeric enzyme, essential for the proper expression of the plastid genome during chloroplast biogenesis. It is especially required for the light initiated expression of photosynthesis genes and the subsequent build-up of the photosynthetic apparatus. The PEP complex is composed of a prokaryotic-type core of four plastid-encoded subunits and 12 nuclear-encoded PEP-associated proteins (PAPs). Among them, there are two iron superoxide dismutases, FSD2/PAP9 and FSD3/PAP4. Superoxide dismutases usually are soluble enzymes not bound into larger protein complexes. To investigate this unusual feature, we characterized PAP9 using molecular genetics, fluorescence microscopy, mass spectrometry, X-ray diffraction, and solution-state NMR. Despite the presence of a predicted nuclear localization signal within the sequence of the predicted chloroplast transit peptide, PAP9 was mainly observed within plastids. Mass spectrometry experiments with the recombinant Arabidopsis PAP9 suggested that monomers and dimers of PAP9 could be associated to the PEP complex. In crystals, PAP9 occurred as a dimeric enzyme that displayed a similar fold to that of the FeSODs or manganese SOD (MnSODs). A zinc ion, instead of the expected iron, was found to be penta-coordinated with a trigonal-bipyramidal geometry in the catalytic center of the recombinant protein. The metal coordination involves a water molecule and highly conserved residues in FeSODs. Solution-state NMR and DOSY experiments revealed an unfolded C-terminal 34 amino-acid stretch in the stand-alone protein and few internal residues interacting with the rest of the protein. We hypothesize that this C-terminal extension had appeared during evolution as a distinct feature of the FSD2/PAP9 targeting it to the PEP complex. Close vicinity to the transcriptional apparatus may allow for the protection against the strongly oxidizing aerial environment during plant conquering of terrestrial habitats.
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Affiliation(s)
- Adrien Favier
- Université Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France
| | - Pierre Gans
- Université Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France
| | | | - Luca Signor
- Université Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France
| | | | | | - Robert Blanvillain
- Université Grenoble-Alpes, CNRS, CEA, INRA, IRIG-LPCV, Grenoble, France
- *Correspondence: Robert Blanvillain,
| | - David Cobessi
- Université Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France
- David Cobessi,
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4
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Chung WH. Unraveling new functions of superoxide dismutase using yeast model system: Beyond its conventional role in superoxide radical scavenging. J Microbiol 2017; 55:409-416. [PMID: 28281199 DOI: 10.1007/s12275-017-6647-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Revised: 01/31/2017] [Accepted: 01/31/2017] [Indexed: 01/16/2023]
Abstract
To deal with chemically reactive oxygen molecules constantly threatening aerobic life, cells are readily equipped with elaborate biological antioxidant systems. Superoxide dismutase is a metalloenzyme catalytically eliminating superoxide radical as a first-line defense mechanism against oxidative stress. Multiple different SOD isoforms have been developed throughout evolution to play distinct roles in separate subcellular compartments. SOD is not essential for viability of most aerobic organisms and intriguingly found even in strictly anaerobic bacteria. Sod1 has recently been known to play important roles as a nuclear transcription factor, an RNA binding protein, a synthetic lethal interactor, and a signal modulator in glucose metabolism, most of which are independent of its canonical function as an antioxidant enzyme. In this review, recent advances in understanding the unconventional role of Sod1 are highlighted and discussed with an emphasis on its genetic crosstalk with DNA damage repair/checkpoint pathways. The budding yeast Saccharomyces cerevisiae has been successfully used as an efficient tool and a model organism to investigate a number of novel functions of Sod1.
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Affiliation(s)
- Woo-Hyun Chung
- College of Pharmacy, Duksung Women's University, Seoul, 01369, Republic of Korea. .,Innovative Drug Center, Duksung Women's University, Seoul, 01369, Republic of Korea.
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5
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Flint A, Stintzi A, Saraiva LM. Oxidative and nitrosative stress defences of Helicobacter and Campylobacter species that counteract mammalian immunity. FEMS Microbiol Rev 2016; 40:938-960. [PMID: 28201757 PMCID: PMC5091033 DOI: 10.1093/femsre/fuw025] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 03/29/2016] [Accepted: 07/02/2016] [Indexed: 12/18/2022] Open
Abstract
Helicobacter and Campylobacter species are Gram-negative microaerophilic host-associated heterotrophic bacteria that invade the digestive tract of humans and animals. Campylobacter jejuni is the major worldwide cause of foodborne gastroenteritis in humans, while Helicobacter pylori is ubiquitous in over half of the world's population causing gastric and duodenal ulcers. The colonisation of the gastrointestinal system by Helicobacter and Campylobacter relies on numerous cellular defences to sense the host environment and respond to adverse conditions, including those imposed by the host immunity. An important antimicrobial tool of the mammalian innate immune system is the generation of harmful oxidative and nitrosative stresses to which pathogens are exposed during phagocytosis. This review summarises the regulators, detoxifying enzymes and subversion mechanisms of Helicobacter and Campylobacter that ultimately promote the successful infection of humans.
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Affiliation(s)
- Annika Flint
- Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
| | - Alain Stintzi
- Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
| | - Lígia M. Saraiva
- Instituto de Tecnologia Química e Biológica, NOVA, Av. da República, 2780-157 Oeiras, Portugal
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Watson E, Sherry A, Inglis NF, Lainson A, Jyothi D, Yaga R, Manson E, Imrie L, Everest P, Smith DGE. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity. EUPA OPEN PROTEOMICS 2014; 4:184-194. [PMID: 27525220 PMCID: PMC4975774 DOI: 10.1016/j.euprot.2014.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 06/19/2014] [Indexed: 12/24/2022]
Abstract
Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC-ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith-Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.
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Affiliation(s)
- Eleanor Watson
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | - Aileen Sherry
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - Neil F Inglis
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | - Alex Lainson
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | | | - Raja Yaga
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | - Erin Manson
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | - Lisa Imrie
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom
| | - Paul Everest
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | - David G E Smith
- Moredun Research Institute, Bush Loan, Penicuik, United Kingdom; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
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7
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Zanotti G, Cendron L. Structural and functional aspects of the Helicobacter pylori secretome. World J Gastroenterol 2014; 20:1402-1423. [PMID: 24587618 PMCID: PMC3925851 DOI: 10.3748/wjg.v20.i6.1402] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Proteins secreted by Helicobacter pylori (H. pylori), an important human pathogen responsible for severe gastric diseases, are reviewed from the point of view of their biochemical characterization, both functional and structural. Despite the vast amount of experimental data available on the proteins secreted by this bacterium, the precise size of the secretome remains unknown. In this review, we consider as secreted both proteins that contain a secretion signal for the periplasm and proteins that have been detected in the external medium in in vitro experiments. In this way, H. pylori’s secretome appears to be composed of slightly more than 160 proteins, but this number must be considered very cautiously, not only because the definition of secretome itself is ambiguous but also because the included proteins were observed as secreted in in vitro experiments that were not representative of the environmental situation in vivo. The proteins that appear to be secreted can be grouped into different classes: enzymes (48 proteins), outer membrane proteins (43), components of flagella (11), members of the cytotoxic-associated genes pathogenicity island or other toxins (8 and 5, respectively), binding and transport proteins (9), and others (11). A final group, which includes 28 members, is represented by hypothetical uncharacterized proteins. Despite the large amount of data accumulated on the H. pylori secretome, a considerable amount of work remains to reach a full comprehension of the system at the molecular level.
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8
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Tsugawa H. [Study of infection strategies of Helicobacter pylori and host cell response against CagA oncoprotein]. Nihon Saikingaku Zasshi 2014; 69:565-575. [PMID: 25447982 DOI: 10.3412/jsb.69.565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Chronic infection with Helicobacter pylori is involved in a variety of clinical outcomes including gastric cancer. In the present study, we focused on the infection strategies of H. pylori associated with establishment of chronic infection. As a result, the following four findings revealed. 1) alpha-ketoglutarate oxidoreductase (KOR) is an essential survival enzyme for energy metabolism in the coccoid form of H. pylori, and inactivation of the KOR activity exerted a potent bactericidal action against H. pylori by preventing induction of the coccoid form. 2) SodB expression is derepressed by amino acids mutation of ferric uptake regulator (Fur), which is associated with the development of Metronidazole resistance. 3) FecA1 is an important determinant of the host-colonization ability through Fe(2+) supply to SodB, suggesting that FecA1 may be a possible target for the development of a novel bactericidal drug. 4) Intracellular CagA oncoprotein is degraded by autophagy and therefore short lived. However, in the CD44v9-expressing gastric cells, CagA specifically accumulated through the repression of autophagy induction.
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Affiliation(s)
- Hitoshi Tsugawa
- Department of Biochemistry & Integrative Medical Biology, School of Medicine, Keio University
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9
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Molecular approaches and modern clinical strategies for the management of Helicobacter pylori infection in Japan. Keio J Med 2013; 61:109-19. [PMID: 23324305 DOI: 10.2302/kjm.2012-0001-re] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Thirty years have passed since Warren and Marshall's discovery of Helicobacter pylori (H. pylori). Since then, not only peptic ulcer diseases and chronic gastritis but also non-cardia gastric cancers have been recognized as diseases originating from H. pylori infection. Several combination therapies consisting of multiple antibiotics have been developed as first- or second-line regimens to eradicate H. pylori infection. Our extensive experience in the field of anti-H. pylori medicine suggests that clinicians should consider a possible role for unidentified, invisible pathogens to elucidate the pathogenesis and improve the treatment of refractory diseases of unknown etiology.
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10
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Dhar MS, Gupta V, Virdi JS. Detection, distribution and characterization of novel superoxide dismutases from Yersinia enterocolitica Biovar 1A. PLoS One 2013; 8:e63919. [PMID: 23704955 PMCID: PMC3660340 DOI: 10.1371/journal.pone.0063919] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Accepted: 04/09/2013] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Superoxide dismutases (SODs) cause dismutation of superoxide radicals to hydrogen peroxide and oxygen. Besides protecting the cells against oxidative damage by endogenously generated oxygen radicals, SODs play an important role in intraphagocytic survival of pathogenic bacteria. The complete genome sequences of Yersinia enterocolitica strains show presence of three different sod genes. However, not much is known about the types of SODs present in Y. enterocolitica, their characteristics and role in virulence and intraphagocytic survival of this organism. METHODOLOGY/PRINCIPAL FINDINGS This study reports detection and distribution of the three superoxide dismutase (sodA, sodB and sodC) genes in 59 strains of Y. enterocolitica and related species. The majority (94%) of the strains carried all three genes and constitutive expression of sodA and sodB was detected in 88% of the strains. Expression of sodC was not observed in any of the strains. The sodA, sodB and sodC genes of Y. enterocolitica were cloned in pET28a (+) vector. Recombinant SodA (82 kDa) and SodB (21 kDa) were expressed as homotetramer and monomer respectively, and showed activity over a broad range of pH (3.0-8.0) and temperature (4-70°C). SodA and SodB showed optimal activity at 4°C under acidic pH of 6.0 and 4.0 respectively. The secondary structures of recombinant SodA and SodB were studied using circular dichroism. Production of YeSodC was not observed even after cloning and expression in E. coli BL21(DE3) cells. A SodA(-) SodB(-) Escherichia coli strain which was unable to grow in medium supplemented with paraquat showed normal growth after complementation with Y. enterocolitica SodA or SodB. CONCLUSIONS/SIGNIFICANCE This is the first report on the distribution and characterization of superoxide dismutases from Y. enterocolitica. The low pH optima of both SodA and SodB encoded by Y. enterocolitica seem to implicate their role in acidic environments such as the intraphagocytic vesicles.
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Affiliation(s)
- Mahesh Shanker Dhar
- Microbial Pathogenicity Laboratory, Department of Microbiology, University of Delhi South Campus, New Delhi, India
| | - Vatika Gupta
- Microbial Pathogenicity Laboratory, Department of Microbiology, University of Delhi South Campus, New Delhi, India
| | - Jugsharan Singh Virdi
- Microbial Pathogenicity Laboratory, Department of Microbiology, University of Delhi South Campus, New Delhi, India
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11
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Morishita K, Takeuchi H, Morimoto N, Shimamura T, Kadota Y, Tsuda M, Taniguchi T, Ukeda H, Yamamoto T, Sugiura T. Superoxide dismutase activity of Helicobacter pylori per se from 158 clinical isolates and the characteristics. Microbiol Immunol 2012; 56:262-72. [PMID: 22289088 DOI: 10.1111/j.1348-0421.2012.00433.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Tsugawa H, Suzuki H, Matsuzaki J, Hirata K, Hibi T. FecA1, a bacterial iron transporter, determines the survival of Helicobacter pylori in the stomach. Free Radic Biol Med 2012; 52:1003-10. [PMID: 22245091 DOI: 10.1016/j.freeradbiomed.2011.12.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Revised: 11/16/2011] [Accepted: 12/14/2011] [Indexed: 01/14/2023]
Abstract
Helicobacter pylori encodes a single iron-cofactored superoxide dismutase (SodB), which is regulated by the ferric uptake regulator (Fur). Ferrous ion (Fe(2+)) is necessary for the activation of SodB. The activity of SodB is an important determinant of the capability of H. pylori for long-term colonization of the stomach and of the development of metronidazole (Mtz) resistance of the bacterium. This study is conducted to characterize the Fe(2+)-supply mechanisms for the activation of SodB in H. pylori, which, as mentioned above, is associated with the host-colonization ability and Mtz resistance of H. pylori. In this study, we demonstrate that fecA1, a Fe(3+)-dicitrate transporter homolog, is an essential gene for SodB activation, but not for the biogenic activity of H. pylori. H. pylori with SodB inactivation by fecA1 deletion showed reduced resistance to H(2)O(2), reduced gastric mucosal-colonization ability in Mongolian gerbils, and also reduced resistance to Mtz. Our experiment demonstrated that FecA1 is an important determinant of the host-colonization ability and Mtz resistance of H. pylori through Fe(2+) supply to SodB, suggesting that FecA1 may be a possible target for the development of a novel bactericidal drug.
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Affiliation(s)
- Hitoshi Tsugawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
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Stent A, Every AL, Sutton P. Helicobacter pylori defense against oxidative attack. Am J Physiol Gastrointest Liver Physiol 2012; 302:G579-87. [PMID: 22194421 DOI: 10.1152/ajpgi.00495.2011] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori is a microaerophilic, gram-negative pathogen of the human stomach. Despite the chronic active gastritis that develops following colonization, H. pylori is able to persist unharmed in the stomach for decades. Much of the damage caused by gastric inflammation results from the accumulation of reactive oxygen/nitrogen species within the stomach environment, which can induce oxidative damage in a wide range of biological molecules. Without appropriate defenses, this oxidative damage would be able to rapidly kill nearby H. pylori, but the organism employs a range of measures, including antioxidant enzymes, biological repair systems, and inhibitors of oxidant generation, to counter the attack. Despite the variety of measures employed to defend against oxidative injury, these processes are intimately interdependent, and any deficiency within the antioxidant system is generally sufficient to cause substantial impairment of H. pylori viability and persistence. This review provides an overview of the development of oxidative stress during H. pylori gastritis and examines the methods the organism uses to survive the resultant damage.
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Affiliation(s)
- Andrew Stent
- Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia
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14
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Suzuki H, Nishizawa T, Tsugawa H, Mogami S, Hibi T. Roles of oxidative stress in stomach disorders. J Clin Biochem Nutr 2011; 50:35-9. [PMID: 22247598 PMCID: PMC3246180 DOI: 10.3164/jcbn.11-115sr] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Accepted: 09/29/2011] [Indexed: 12/13/2022] Open
Abstract
The stomach is a sensitive digestive organ that is susceptible and exposed to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, as well as functional disorders such as functional dyspepsia. In particular, the bacterium Helicobacter pylori plays a major role in eliciting and confronting oxidative stress in the stomach. The present paper summarizes the pathogenesis of oxidative stress in the stomach during the development of various stomach diseases.
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Affiliation(s)
- Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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15
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Miller AF. Superoxide dismutases: ancient enzymes and new insights. FEBS Lett 2011; 586:585-95. [PMID: 22079668 DOI: 10.1016/j.febslet.2011.10.048] [Citation(s) in RCA: 361] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 10/27/2011] [Accepted: 10/30/2011] [Indexed: 11/25/2022]
Abstract
Superoxide dismutases (SODs) catalyze the de toxification of superoxide. SODs therefore acquired great importance as O(2) became prevalent following the evolution of oxygenic photosynthesis. Thus the three forms of SOD provide intriguing insights into the evolution of the organisms and organelles that carry them today. Although ancient organisms employed Fe-dependent SODs, oxidation of the environment made Fe less bio-available, and more dangerous. Indeed, modern lineages make greater use of homologous Mn-dependent SODs. Our studies on the Fe-substituted MnSOD of Escherichia coli, as well as redox tuning in the FeSOD of E. coli shed light on how evolution accommodated differences between Fe and Mn that would affect SOD performance, in SOD proteins whose activity is specific to one or other metal ion.
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Affiliation(s)
- Anne-Frances Miller
- Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
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Atack JM, Kelly DJ. Oxidative stress in Campylobacter jejuni: responses, resistance and regulation. Future Microbiol 2009; 4:677-90. [PMID: 19659424 DOI: 10.2217/fmb.09.44] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Campylobacter jejuni is a major food-borne human pathogen that paradoxically is an oxygen-sensitive microaerophile, yet must resist the oxidative stresses encountered both in the host and in the environment. Recent studies suggest that, perhaps surprisingly, C. jejuni contains a wide range of enzymes involved in oxidative stress defense, and this review focuses on the properties and roles of these proteins. Although the mechanisms of gene regulation are still poorly understood in C. jejuni, several regulators of the oxidative stress response have been identified and their properties are discussed here. We suggest that future studies should be directed towards identifying the role of additional and less well characterized components involved in oxidative stress resistance, as well as providing a more complete picture of the underlying sensing and regulatory mechanisms.
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Affiliation(s)
- John M Atack
- Centre for Chemical Biology, Department of Chemistry, Krebs Institute, The University of Sheffield, Sheffield, S3 7HF, UK
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