TolC-Dependent Exclusion of Porphyrins in
            <i>Escherichia coli</i>

Tatsumi, Rei; Wachi, Masaaki

doi:10.1128/jb.00595-08

Cited by 46 publications

(47 citation statements)

References 47 publications

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“…Heme export systems have also been proposed as a means by which bacteria protect themselves from heme toxicity (2). Although a heme exporter has not been identified in Brucella strains, genes that potentially encode orthologs of proteins linked to porphyrin (34) and heme (24) export in other bacteria can be found in the genome sequence of B. abortus 2308.…”

Section: Resultsmentioning

confidence: 99%

The bhuQ Gene Encodes a Heme Oxygenase That Contributes to the Ability of Brucella abortus 2308 To Use Heme as an Iron Source and Is Regulated by Irr

et al. 2012

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The Brucella BhuQ protein is a homolog of the Bradyrhizobium japonicum heme oxygenases HmuD and HmuQ. To determine if this protein plays a role in the ability of Brucella abortus 2308 to use heme as an iron source, an isogenic bhuQ mutant was constructed and its phenotype evaluated. Although the Brucella abortus bhuQ mutant DCO1 did not exhibit a defect in its capacity to use heme as an iron source or evidence of increased heme toxicity in vitro, this mutant produced increased levels of siderophore in response to iron deprivation compared to 2308. Introduction of a bhuQ mutation into the B. abortus dhbC mutant BHB2 (which cannot produce siderophores) resulted in a severe growth defect in the dhbC bhuQ double mutant JFO1 during cultivation under iron-restricted conditions, which could be rescued by the addition of FeCl 3 , but not heme, to the growth medium. The bhuQ gene is cotranscribed with the gene encoding the iron-responsive regulator RirA, and both of these genes are repressed by the other major iron-responsive regulator in the alphaproteobacteria, Irr. The results of these studies suggest that B. abortus 2308 has at least one other heme oxygenase that works in concert with BhuQ to allow this strain to efficiently use heme as an iron source. The genetic organization of the rirA-bhuQ operon also provides the basis for the proposition that BhuQ may perform a previously unrecognized function by allowing the transcriptional regulator RirA to recognize heme as an iron source. Iron represents an essential micronutrient for Brucella strains (27). Acquiring sufficient iron to meet their physiological needs is particularly challenging for the brucellae because these bacteria are found in nature almost exclusively in mammalian hosts, an environment where the iron restriction faced by pathogenic microbes is well documented (29). Brucella strains can use heme as an iron source in vitro, and studies with an isogenic mutant have shown that the presence of the TonB-dependent outer membrane heme transporter BhuA is required for the wild-type virulence of B. abortus 2308 in experimentally infected mice (21), suggesting that heme is a biologically relevant source of iron for the brucellae during infection.Heme oxygenases catalyze the release of iron from heme, and these enzymes contribute to the ability of a variety of bacteria to utilize heme as an iron source (25,30,37). The product of the gene designated BMEII0706 in the Brucella melitensis 16M genome sequence shares 58 and 50% amino acid identity with the heme oxygenases HmuD and HmuQ, respectively, from Bradyrhizobium japonicum, and this Brucella protein exhibits heme oxygenase activity in an in vitro assay (23). Based on its documented biochemical activity and its homology to the IsdG/HmuQ family of heme oxygenases, we have given this protein the designation BhuQ (Brucella heme utilization oxygenase Q). The purpose of the experiments described in this report was to determine if the homologous protein in Brucella abortus 2308 (which is encoded by BAB2_0677) plays a rol...

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Section: Resultsmentioning

confidence: 99%

The bhuQ Gene Encodes a Heme Oxygenase That Contributes to the Ability of Brucella abortus 2308 To Use Heme as an Iron Source and Is Regulated by Irr

et al. 2012

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“…We propose that the deferrochelation activity represents their physiological function, enabling heme iron acquisition without internalization of heme, a potentially hazardous substance in the case of EfeB orthologs and without production of CO, an antibacterial gas. Porphyrins and heme efflux pumps have been identified in several organisms (27,28). In addition, EfeB orthologs are present in many Gram-positive species.…”

Section: Discussionmentioning

confidence: 99%

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Létoffé

Heuck

Delepelaire

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

134

126

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Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme

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“…For tolC mutants, efflux of the cell-synthesized metabolites cysteine (12), porphyrins (13), and cAMP (14) was decreased, but no specific pump was identified. Biofilm formation was decreased in cells with deletions in either emrD or emrE or in any one of the following TolC-dependent pump genes: acrD, acrE, emrK, or mdtE (15).…”

mentioning

confidence: 99%

Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

Rosner

Martin

2012

Journal of Bacteriology

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Escherichia coli has nine inner membrane efflux pumps which complex with the outer membrane protein TolC and cognate membrane fusion proteins to form tripartite transperiplasmic pumps with diverse functions, including the expulsion of antibiotics. We recently observed that tolC mutants have elevated activities for three stress response regulators, MarA, SoxS, and Rob, and we suggested that TolC-dependent efflux is required to prevent the accumulation of stressful cellular metabolites. Here, we used spy::lacZ fusions to show that two systems for sensing/repairing extracytoplasmic stress, BaeRS and CpxARP, are activated in the absence of TolC-dependent efflux. In either tolC mutants or bacteria with mutations in the genes for four TolC-dependent efflux pumps, spy expression was increased 6-to 8-fold. spy encodes a periplasmic chaperone regulated by the BaeRS and CpxARP stress response systems. The overexpression of spy in tolC or multiple efflux pump mutants also depended on these systems. spy overexpression was not due to acetate, ethanol, or indole accumulation, since external acetate had only a minor effect on wild-type cells, ethanol had a large effect that was not CpxA dependent, and a tolC tnaA mutant which cannot accumulate internal indole overexpressed spy. We propose that, unless TolC-dependent pumps excrete certain metabolites, the metabolites accumulate and activate at least five different stress response systems.

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TolC-Dependent Exclusion of Porphyrins in Escherichia coli

Cited by 46 publications

References 47 publications

The bhuQ Gene Encodes a Heme Oxygenase That Contributes to the Ability of Brucella abortus 2308 To Use Heme as an Iron Source and Is Regulated by Irr

The bhuQ Gene Encodes a Heme Oxygenase That Contributes to the Ability of Brucella abortus 2308 To Use Heme as an Iron Source and Is Regulated by Irr

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

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