Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog

ABSTRACT Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

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Contribution of a PerR-like regulator to the oxidative-stress response and virulence of Enterococcus faecalis

Microbiology ◽

10.1099/mic.0.28325-0 ◽

2005 ◽

Vol 151 (12) ◽

pp. 3997-4004 ◽

Cited By ~ 41

Author(s):

Nicolas Verneuil ◽

Alain Rincé ◽

Maurizio Sanguinetti ◽

Brunella Posteraro ◽

Giovanni Fadda ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Enterococcus Faecalis ◽

Oxidative Stress Response ◽

Homologous Gene ◽

Wild Type ◽

Real Time Quantitative Pcr ◽

Phenotype Analysis ◽

In The Wild ◽

Peritonitis Model

PerR is one of the most important transcriptional regulators involved in the oxidative-stress response in Bacillus subtilis. Here, the homologous gene in Enterococcus faecalis, ranked among the leading causes of nosocomial infection, was characterized and analysed. Phenotype analysis showed that the perR mutant was significantly more resistant to H2O2 challenge (P<0·05). Expression of eight genes with potential roles in the oxidative-stress response was determined in the wild-type and perR-mutant strains by real-time quantitative PCR. Surprisingly, low quantitative differences in the transcriptional activity of these genes in the mutant versus wild-type were observed. Likewise, this locus was not involved in survival within murine macrophages, but in the mouse peritonitis model, the perR mutant appeared less lethal than the JH2-2 wild-type strain. The combined results show that PerR affects E. faecalis virulence and that its implication in the transcriptional regulation in this bacterium deviates from the B. subtilis model.

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Autoinducer-2 Triggers the Oxidative Stress Response in Mycobacterium avium, Leading to Biofilm Formation

Applied and Environmental Microbiology ◽

10.1128/aem.02066-07 ◽

2008 ◽

Vol 74 (6) ◽

pp. 1798-1804 ◽

Cited By ~ 51

Author(s):

Henriette Geier ◽

Serge Mostowy ◽

Gerard A. Cangelosi ◽

Marcel A. Behr ◽

Timothy E. Ford

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Quorum Sensing ◽

Mycobacterium Avium ◽

Biofilm Formation ◽

Transcriptional Response ◽

Opportunistic Pathogen ◽

Environmental Stresses ◽

Oxidative Stress Response ◽

Autoinducer 2

ABSTRACT Mycobacterium avium is an environmental organism and opportunistic pathogen with inherent resistance to drugs, environmental stresses, and the host immune response. To adapt to these disparate conditions, M. avium must control its transcriptional response to environmental cues. M. avium forms biofilms in various environmental settings, including drinking water pipes and potable water reservoirs. In this study, we investigated the role of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation by M. avium. The addition of the compound to planktonic M. avium cultures resulted in increased biofilm formation. Microarray and reverse transcriptase PCR studies revealed an upregulation of the oxidative stress response upon addition of AI-2. This suggests that the response to AI-2 might be related to oxidative stress, rather than quorum sensing. Consistent with this model, addition of hydrogen peroxide, a known stimulus of the oxidative stress response, to M. avium cultures resulted in elevated biofilm formation. These results suggest that AI-2 does not act as a quorum-sensing signal in M. avium. Instead, biofilm formation is triggered by environmental stresses of biotic and abiotic origins and AI-2 may exert effects on that level.

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Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7318796 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Vittoria Cenni ◽

Snezana Kojic ◽

Cristina Capanni ◽

Georgine Faulkner ◽

Giovanna Lattanzi

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Stress Response ◽

Muscular Dystrophy ◽

Transcriptional Response ◽

Oxidative Stress Response ◽

Ankyrin Repeat ◽

Lamin A ◽

Cellular Reactive Oxygen Species ◽

Cardiac Muscles

Ankrd2 (ankyrin repeats containing domain 2) or Arpp (ankyrin repeat, PEST sequence, and proline-rich region) is a member of the muscle ankyrin repeat protein family. Ankrd2 is mostly expressed in skeletal muscle, where it plays an intriguing role in the transcriptional response to stress induced by mechanical stimulation as well as by cellular reactive oxygen species. Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response. In this review, besides describing the latest advances related to Ankrd2 studies, including novel discoveries on Ankrd2 isoform-specific functions, we report the main findings on the relationship of Ankrd2 with A-type lamins and discuss known and potential mechanisms involving defective Ankrd2-lamin A interplay in the pathogenesis of muscular laminopathies.

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Virulence of Streptococcus pneumoniae: PsaA Mutants Are Hypersensitive to Oxidative Stress

Infection and Immunity ◽

10.1128/iai.70.3.1635-1639.2002 ◽

2002 ◽

Vol 70 (3) ◽

pp. 1635-1639 ◽

Cited By ~ 105

Author(s):

Hsing-Ju Tseng ◽

Alastair G. McEwan ◽

James C. Paton ◽

Michael P. Jennings

Keyword(s):

Oxidative Stress ◽

Streptococcus Pneumoniae ◽

Stress Response ◽

Nadh Oxidase ◽

Redox Homeostasis ◽

Oxidative Stress Response ◽

Wild Type ◽

Regulation Of Expression ◽

Altered Expression ◽

Transport Complex

ABSTRACT psaA encodes a 37-kDa pneumococcal lipoprotein which is part of an ABC Mn(II) transport complex. Streptococcus pneumoniae D39 psaA mutants have previously been shown to be significantly less virulent than wild-type D39, but the mechanism underlying the attenuation has not been resolved. In this study, we have shown that psaA and psaD mutants are highly sensitive to oxidative stress, i.e., to superoxide and hydrogen peroxide, which might explain why they are less virulent than the wild-type strain. Our investigations revealed altered expression of the key oxidative-stress response enzymes superoxide dismutase and NADH oxidase in psaA and psaD mutants, suggesting that PsaA and PsaD may play important roles in the regulation of expression of oxidative-stress response enzymes and intracellular redox homeostasis.

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Iron homeostasis and management of oxidative stress response in bacteria

Metallomics ◽

10.1039/c1mt00022e ◽

2011 ◽

Vol 3 (6) ◽

pp. 540 ◽

Cited By ~ 134

Author(s):

Pierre Cornelis ◽

Qing Wei ◽

Simon C. Andrews ◽

Tiffany Vinckx

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Iron Homeostasis ◽

Oxidative Stress Response

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Proteomic analysis reveals modulation of iron homeostasis and oxidative stress response in Pseudomonas aeruginosa PAO1 by curcumin inhibiting quorum sensing regulated virulence factors and biofilm production

Journal of Proteomics ◽

10.1016/j.jprot.2016.04.019 ◽

2016 ◽

Vol 145 ◽

pp. 112-126 ◽

Cited By ~ 30

Author(s):

Sivasamy Sethupathy ◽

Krishnan Ganesh Prasath ◽

Sivagnanam Ananthi ◽

Sundarasamy Mahalingam ◽

Samiraj Yesu Balan ◽

...

Keyword(s):

Oxidative Stress ◽

Pseudomonas Aeruginosa ◽

Stress Response ◽

Virulence Factors ◽

Proteomic Analysis ◽

Iron Homeostasis ◽

Oxidative Stress Response ◽

Pseudomonas Aeruginosa Pao1 ◽

Biofilm Production ◽

And Oxidative Stress

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The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes

Infection and Immunity ◽

10.1128/iai.70.9.4968-4976.2002 ◽

2002 ◽

Vol 70 (9) ◽

pp. 4968-4976 ◽

Cited By ~ 65

Author(s):

Susanna Ricci ◽

Robert Janulczyk ◽

Lars Björck

Keyword(s):

Oxidative Stress ◽

Streptococcus Pyogenes ◽

Stress Responses ◽

Metal Binding ◽

Iron Homeostasis ◽

Bacterial Species ◽

Transcriptional Analysis ◽

Wild Type ◽

Allelic Replacement

ABSTRACT Ferric uptake regulator (Fur) and Fur-like proteins form an important family of transcriptional regulators in many bacterial species. In this work we have characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype of Streptococcus pyogenes. To determine the role of PerR in S. pyogenes, we inactivated the gene by allelic replacement. PerR-deficient bacteria showed 48% reduction of 55Fe incorporation from the culture medium. Transcriptional analysis revealed that mtsA, encoding a metal-binding protein of an ABC transporter in S. pyogenes, was transcribed at lower levels than were wild-type cells. Although total iron accumulation was reduced, the growth of the mutant strain was not significantly hampered. The mutant showed hyperresistance to hydrogen peroxide, and this response was induced in wild-type cells by growth in aerobiosis, suggesting that PerR acts as an oxidative stress-responsive repressor. PerR may also participate in the response to superoxide stress, as the perR mutant was more sensitive to the superoxide anion and had a reduced transcription of sodA, which encodes the sole superoxide dismutase of S. pyogenes. Complementation of the mutation with a functional perR gene restored 55Fe incorporation, response to peroxide stress, and transcription of both mtsA and sodA to levels comparable to those of wild-type bacteria. Finally, the perR mutant was attenuated in virulence in a murine air sac model of infection (P < 0.05). These results demonstrate that PerR is involved in the regulation of iron homeostasis and oxidative stress responses and that it contributes to the virulence of S. pyogenes.

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Calcium-binding protein 39 facilitates molecular interaction between Ste20p proline alanine-rich kinase and oxidative stress response 1 monomers

AJP Cell Physiology ◽

10.1152/ajpcell.00284.2012 ◽

2012 ◽

Vol 303 (11) ◽

pp. C1198-C1205 ◽

Cited By ~ 19

Author(s):

José Ponce-Coria ◽

Kenneth B. Gagnon ◽

Eric Delpire

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Calcium Binding ◽

Binding Protein ◽

Oxidative Stress Response ◽

Calcium Binding Protein ◽

Domain Swapping ◽

Xenopus Laevis Oocytes ◽

Wild Type ◽

Kinase Activation

X-ray crystallography of the catalytic domain of oxidative stress response 1 (OSR1) has provided evidence for dimerization and domain swapping. However, the functional significance of dimer formation or domain swapping has yet to be addressed. In this study, we used nine glutamine residues to link the carboxyl end of one SPAK (related Ste20 kinase) monomer to the amino end of another SPAK monomer to assess the role of kinase monomers versus dimers in Na-K-2Cl cotransporter 1 (NKCC1) activation. Transport studies in Xenopus laevis oocytes show that forcing dimerization of two wild-type SPAK molecules results in cotransporter activation when calcium-binding protein 39 (Cab39) is coexpressed, indicating that the presence of Cab39 can bypass the upstream phosphorylation requirement of SPAK normally associated with kinase activation. We determined that monomers are the functional units of the kinase as concatamers consisting of an active and various inactive monomers were still functional. Furthermore, we found that two different nonfunctional SPAK mutants could be linked together in a concatamer and activated, presumably by domain swapping, indicating that dimerization and domain swapping are both important components of kinase activation. Finally, we demonstrate rescue of a nonfunctional SPAK mutant by domain swapping with wild-type OSR1, indicating that heterodimers of the two Ste20-related kinases are possible and therefore potentially relevant to the regulation of NKCC1 activity.

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