Iron acquisition mechanisms of the Burkholderia cepacia complex

Thomas, Mark S.

doi:10.1007/s10534-006-9065-4

Cited by 77 publications

(73 citation statements)

References 143 publications

(222 reference statements)

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“…Although analysis of the genomes of various Burkholderia species has suggested their use of hemin as a sole source of iron, only a few Burkholderia cenocepacia and B. pseudomallei strains have been experimentally confirmed to utilize external hemin (6,25,32). However, the mechanisms for transcriptional regulation of the genes for heme uptake systems in these strains have remained unknown.…”

Section: Discussionmentioning

confidence: 99%

“…representative and well-studied system is siderophore-mediated sequestration of external ferric ion and its subsequent transport into the cytoplasm and reduction to ferrous ion (4)(5)(6). However, high concentrations of intracellular ferrous ion under aerobic conditions are toxic and, for example, induce the Fenton reaction, by which metabolically produced hydrogen peroxide (a toxic reactive oxygen species [ROS]) is converted to hydroxyl radical, another ROS with a greater degree of toxicity (Fe 2ϩ ϩ H 2 O 2 ¡ Fe 3ϩ ϩ HO Ϫ ϩ OH·) (7).…”

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confidence: 99%

“…Under iron-replete conditions, the Fur-Fe 2ϩ complex interacts with a specific sequence (Fur box), usually leading to the transcriptional repression of genes that are located downstream of the Fur box. Fur is a global transcriptional regulator and regulates, either directly or indirectly, the transcription of a number of genes that are related to the acquisition and utilization of iron sources; Fur has also been indicated to regulate many genes that are not related to these functions (6,12). A number of bacterial species possess, in addition to the siderophore-mediated iron uptake systems, other systems for the uptake of external heme as a sole iron source, and TonB-dependent ABC-type heme transport systems are usually involved in the uptake of heme into the cytoplasm, where ferrous ion is released from heme (13)(14)(15)(16)(17)(18)(19).…”

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confidence: 99%

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The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616

Sato

Nonoyama

Kimura

et al. 2017

Appl Environ Microbiol

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Iron and heme play very important roles in various metabolic functions in bacteria, and their intracellular homeostasis is maintained because high concentrations of free forms of these molecules greatly facilitate the Fenton reaction-mediated production of large amounts of reactive oxygen species that severely damage various biomolecules. The ferric uptake regulator (Fur) from Burkholderia multivorans ATCC 17616 is an iron-responsive global transcriptional regulator, and its fur deletant exhibits pleiotropic phenotypes. In this study, we found that the phenotypes of the fur deletant were suppressed by an additional mutation in hemP. The transcription of hemP was negatively regulated by Fur under iron-replete conditions and was constitutive in the fur deletant. Growth of a hemP deletant was severely impaired in a medium containing hemin as the sole iron source, demonstrating the important role of HemP in hemin utilization. HemP was required as a transcriptional activator that specifically binds the promoter-containing region upstream of a Fur-repressive hmuRSTUV operon, which encodes the proteins for hemin uptake. A hmuR deletant was still able to grow using hemin as the sole iron source, albeit at a rate clearly lower than that of the wild-type strain. These results strongly suggested (i) the involvement of HmuR in hemin uptake and (ii) the presence in ATCC 17616 of at least part of other unknown hemin uptake systems whose expression depends on the HemP function. Our in vitro analysis also indicated high-affinity binding of HemP to hemin, and such a property might modulate transcriptional activation of the hmu operon.IMPORTANCE Although the hmuRSTUV genes for the utilization of hemin as a sole iron source have been identified in a few Burkholderia strains, the regulatory expression of these genes has remained unknown. Our analysis in this study using B. multivorans ATCC 17616 showed that its HemP protein is required for expression of the hmuRSTUV operon, and the role of HemP in betaproteobacterial species was elucidated for the first time, to our knowledge, in this study. The HemP protein was also found to have two additional properties that have not been reported for functional homologues in other species; one is that HemP is able to bind to the promotercontaining region of the hmu operon to directly activate its transcription, and the other is that HemP is also required for the expression of an unknown hemin uptake system.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616

Sato

Nonoyama

Kimura

et al. 2017

Appl Environ Microbiol

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“…Bcc species produce one or more of four siderophores: ornibactin, pyochelin, cepabactin, and cepaciachelin, which bind ferric iron and transport it back into the cell via specific receptor mediated membrane associated uptake mechanisms (Thomas 2007;Darling et al 1998). Ornibactin is the most abundantly produced and genes involved in both ornibactin and pyochelin synthesis and transport have been identified (Sokol et al 1999(Sokol et al , 2000Visser et al 2004;Agnoli et al 2006;Thomas 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Ornibactin is the most abundantly produced and genes involved in both ornibactin and pyochelin synthesis and transport have been identified (Sokol et al 1999(Sokol et al , 2000Visser et al 2004;Agnoli et al 2006;Thomas 2007).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia

Tyrrell¹,

Whelan²,

Wright³

et al. 2015

Biometals

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Burkholderia cenocepacia is a bacterial pathogen which causes severe respiratory infections in cystic fibrosis (CF). These studies were aimed at gaining an insight into the iron acquisition strategies of B. cenocepacia. In iron restricted conditions, genes associated with the synthesis and utilisation of ornibactin (pvdA, orbA, orb F) were significantly upregulated compared to the expression of pyochelin associated genes (pchD, fptA). In the absence of alternative iron sources, B. cenocepacia J2315 and 715j utilised ferritin and haemin, but not transferrin or lactoferrin for growth. Significantly, mutants unable to produce ornibactin, (715j-orbI) or ornibactin and pyochelin, (715j-pobA), utilised haemin and ferritin more efficiently than the wild-type. Moreover, both mutants were also able to utilise lactoferrin for growth (P ≤ 0.01) and additionally 715j-pobA utilised transferrin (P ≤ 0.01), potentially facilitating adaptation to the host environment. Furthermore, B. cenocepacia increased ornibactin gene expression in response to pyoverdine from Pseudomonas aeruginosa (P ≤ 0.01), demonstrating the capacity to compete for iron in co-colonised niches. Pyoverdine also significantly diminished the growth of B. cenocepacia (P < 0.001) which was related to its iron chelating activity. In a study of three B. cenocepacia sequential clonal isolates obtained from a CF patient over a 3.5 year period, ornibactin upregulation in response to pyoverdine was less pronounced in the last isolate compared to the earlier isolates, as was growth in the presence of haemin and ferritin, indicating alternative iron acquisition mechanism(s) may dominate as chronic infection progresses. These data demonstrate the multifaceted iron acquisition strategies of B. cenocepacia and their capacity to be differentially activated in the presence of P. aeruginosa and during chronic infection.

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Identification of the fatty acid coenzyme‐A ligase FadD1 as an interacting partner of FptX in the Pseudomonas aeruginosa pyochelin pathway

2020

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Pseudomonas aeruginosa is one of the most important nosocomial bacteria emerging as a highly multidrug‐resistant pathogen. P. aeruginosa produces two siderophores including pyochelin (PCH) to fulfil its need for iron during infections. We know that both outer and inner membrane proteins FptA and FptX are involved in the ferri‐PCH uptake, but this process requires increasing molecular and biochemical knowledge. Here, using bacterial two‐hybrid and copurification assays we identified the fatty acid coenzyme‐A ligase FadD1 as a novel interacting partner of the inner membrane transporter FptX and found that FadD1 may play a role in PCH production. We managed to purify the FadD1–FptX inner membrane complex and obtained low‐resolution 3D models, opening the way for future high‐resolution structures.

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Iron acquisition mechanisms of the Burkholderia cepacia complex

Cited by 77 publications

References 143 publications

The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616

The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia

Identification of the fatty acid coenzyme‐A ligase FadD1 as an interacting partner of FptX in the Pseudomonas aeruginosa pyochelin pathway

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