Cytotoxicity of Pseudomonas Secreted Exotoxins Requires OxyR Expression

Melstrom, Kurt; Kozlowski, Ryan; Hassett, Daniel J.; Suzuki, Hitoshi; Bates, Donna M.; Gamelli, Richard L.; Shankar, Ravi

doi:10.1016/j.jss.2007.02.046

Cited by 16 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous results from our group already established a similar link between oxidative stress and inhibition of siderophore-mediated iron uptake in pseudomonads, because the inactivation of the cytochrome c biogenesis gene ccmC resulted in increased oxidative stress and impaired utilization of ferrisiderophores (Baysse et al, 2003;Baert et al, 2008). Our results partially explain why a P. aeruginosa oxyR mutant shows a decreased virulence in animal models (Lau et al, 2005;Melstrom et al, 2007). (1), oxyR mutant (2), complemented oxyR with pBBR-oxyR (3), wild type with pBBR-oxyR (4) and wild type with a pBBR empty vector (5) in CAA1EDDHA (left panel) or in CAA150 mM FeCl 3 (right panel).…”

Section: Discussionsupporting

confidence: 82%

Loss of the oxidative stress regulator OxyR inPseudomonas aeruginosaPAO1 impairs growth under iron-limited conditions

Vinckx¹,

Matthijs²,

Cornélis³

2008

FEMS Microbiology Letters

View full text Add to dashboard Cite

Pyoverdine is the main siderophore secreted by fluorescent pseudomonads to scavenge iron in the extracellular environment. Iron uptake, however, needs to be tightly regulated, because free iron stimulates the formation of highly toxic oxygen derivatives. In the opportunistic pathogen Pseudomonas aeruginosa, the transcriptional regulator OxyR plays a key role in the upregulation of defense mechanisms against oxidative stress as it stimulates the expression of the antioxidant genes katB, ahpB and ahpCF after contact with oxidative stress-generating agents. Inactivation of the oxyR gene in Pseudomonas fluorescens ATCC 17400 and in P. aeruginosa PAO1 impairs pyoverdine-mediated iron uptake. The pyoverdine utilization defect can be restored by complementation with the oxyR gene of P. aeruginosa, as well as by adding catalase. Growth of the oxyR mutant in low- or high-iron media is also impaired at a low, but not at a high inoculum density. Uptake of radioactive (59)Fe pyoverdine is, however, not affected by the oxyR mutation, nor is the transcription of the fpvA gene encoding the ferripyoverdine receptor, suggesting that the defect lies in the inability to remove iron from the ferrisiderophore.

show abstract

Section: Discussionsupporting

confidence: 82%

Loss of the oxidative stress regulator OxyR inPseudomonas aeruginosaPAO1 impairs growth under iron-limited conditions

Vinckx¹,

Matthijs²,

Cornélis³

2008

FEMS Microbiology Letters

View full text Add to dashboard Cite

show abstract

“…There is a growing realization of the role of peroxide-sensing regulators in adapting to this environmental shift through the control of processes such as virulence factor expression (74,90) and biofilm formation (99,119). Furthermore, the lethality of some antibiotics is due, at least in part, to increased production of ROS (58), and it has been demonstrated that the levels of oxidative stress protective enzymes can affect antibiotic resistance levels (6).…”

Section: Resultsmentioning

confidence: 99%

“…In the case of OxyR and PerR, their effect on virulence is not solely related to the regulation of oxidative stress defense genes. OxyR induces the expression of virulence factors that allow pathogens to evade host innate immunity (74,90), while PerR has been shown to directly regulate an extracellular virulence factor (mitogen factor 3) in Streptococcus pyogenes (117). Other clinically relevant processes, such as biofilm formation (99,119) and the oxidation state-independent regulation of several epigenetically controlled promoters determining phase variation (9,113,114), are also regulated by OxyR.…”

Section: Role Of Oxyr Perr and Ohrr In Virulencementioning

confidence: 99%

Peroxide-Sensing Transcriptional Regulators in Bacteria

2012

View full text Add to dashboard Cite

The ability to maintain intracellular concentrations of toxic reactive oxygen species (ROS) within safe limits is essential for all aerobic life forms. In bacteria, as well as other organisms, ROS are produced during the normal course of aerobic metabolism, necessitating the constitutive expression of ROS scavenging systems. However, bacteria can also experience transient high-level exposure to ROS derived either from external sources, such as the host defense response, or as a secondary effect of other seemingly unrelated environmental stresses. Consequently, transcriptional regulators have evolved to sense the levels of ROS and coordinate the appropriate oxidative stress response. Three well-studied examples of these are the peroxide responsive regulators OxyR, PerR, and OhrR. OxyR and PerR are sensors of primarily H 2 O 2 , while OhrR senses organic peroxide (ROOH) and sodium hypochlorite (NaOCl). OxyR and OhrR sense oxidants by means of the reversible oxidation of specific cysteine residues. In contrast, PerR senses H 2 O 2 via the Fe-catalyzed oxidation of histidine residues. These transcription regulators also influence complex biological phenomena, such as biofilm formation, the evasion of host immune responses, and antibiotic resistance via the direct regulation of specific proteins.

show abstract

“…, 2005). Recently, OxyR has also been shown to regulate secretion of potent cytotoxic factors in P. aeruginosa (Melstrom et al. , 2007).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosaOspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection

Lan

Murray²,

Kazmierczak

et al. 2010

Molecular Microbiology

View full text Add to dashboard Cite

SummaryOxidative stress is one of the main challenges bacteria must cope with during infection. Here, we identify a new oxidative stress sensing and response ospR (oxidative stress response and pigment production Regulator) gene in Pseudomonas aeruginosa. Deletion of ospR leads to a significant induction in H2O2 resistance. This effect is mediated by de-repression of PA2826, which lies immediately upstream of ospR and encodes a glutathione peroxidase. Constitutive expression of ospR alters pigment production and b-lactam resistance in P. aeruginosa via a PA2826-independent manner. We further discovered that OspR regulates additional genes involved in quorum sensing and tyrosine metabolism. These regulatory effects are redox-mediated as addition of H2O2 or cumene hydroperoxide leads to the dissociation of OspR from promoter DNA. A conserved Cys residue, Cys-24, plays the major role of oxidative stress sensing in OspR. The serine substitution mutant of Cys-24 is less susceptible to oxidation in vitro and exhibits altered pigmentation and b-lactam resistance. Lastly, we show that an ospR null mutant strain displays a greater capacity for dissemination than wild-type MPAO1 strain in a murine model of acute pneumonia. Thus, OspR is a global regulator that senses oxidative stress and regulates multiple pathways to enhance the survival of P. aeruginosa inside host.

show abstract

Cytotoxicity of Pseudomonas Secreted Exotoxins Requires OxyR Expression

Abstract: Taken together, our data indicate that OxyR regulates the secretion of potent cytotoxic factors by P. aeruginosa.

Cited by 16 publications

References 38 publications

Loss of the oxidative stress regulator OxyR inPseudomonas aeruginosaPAO1 impairs growth under iron-limited conditions

Loss of the oxidative stress regulator OxyR inPseudomonas aeruginosaPAO1 impairs growth under iron-limited conditions

Peroxide-Sensing Transcriptional Regulators in Bacteria

Pseudomonas aeruginosaOspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection

Contact Info

Product

Resources

About