Role and regulation of heme iron acquisition in gram-negative pathogens

Runyen-Janecky, Laura J.

doi:10.3389/fcimb.2013.00055

Cited by 103 publications

(126 citation statements)

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“…2A). Some strains in these species have been shown to utilize extracellular hemin as a sole source of iron (15). Kvitko et al (25) experimentally identified the Burkholderia pseudomallei hmuRSTUV cluster that encodes a TonB-dependent ABC transporter system for the uptake and utilization of hemin, and in the present study we found a similar gene cluster on chromosome 2 in ATCC 17616 ( Fig.…”

Section: Resultssupporting

confidence: 82%

“…Constitutive and highlevel production of HemP in DF1 would be expected to lead to overproduction of HmuS. Some HmuS homologues from other genera have been reported to function as heme oxygenases that degrade heme to release free iron (15,17). If the ATCC 17616 HmuS protein has such an activity, then the overproduced HmuS protein in DF1 would result in drastic increases in the levels of free iron produced from intracellular heme, and the increased levels of free iron would in turn generate large amounts of ROS.…”

Section: Discussionmentioning

confidence: 99%

“…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). Although heme is very important for various metabolic functions in bacteria (20), free intracellular heme is also very toxic, most likely due to the generation of hydroxyl radical by the heme-mediated Fenton reaction (21).…”

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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: Resultssupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…In addition, it is a pivotal component of the innate immune response through its role in the generation of toxic oxygen and nitrogen intermediates [12] . Pathogens are involving growth, proliferation and disease processes, can not directly use Fe 2+ from the host body, but compete with the host for Fe 2+ by iron uptake-related proteins to fulfill their iron needs [13] . TonB protein, a periplasmic protein, plays an important role in energy-dependent transport of iron siderophores of Gram-negative bacteria as well as a virulence factor [14] .…”

Section: Iron (Fe 2+mentioning

confidence: 99%

Çin’de Kanatlı Hayvanlardan İzole Edilen Pasteurella multocida Suşlarının Moleküler Karakterizasyonu ve tonB Geni Açısından Genetik Analizi

Li¹,

Cheng²,

Lan³

et al. 2017

Kafkas Univ Vet Fak Derg

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Pasteurella multocida (P. multocida) causes fowl cholera in birds and the pathogenesis and virulence factors involved are still poorly understood. TonB protein is a periplasmic protein prevalent in a large number of Gram-negative bacteria, as in Pasteurella, which is believed to be responsible for the import of ferric iron complexes across the outer membrane and plays a role as an important virulence factor to help bacteria to obtain nutrients. In this study, a total of 23 isolates of P. multocida were obtained from 172 cases of clinical respiratory disease in duck and geese, giving an isolation rate of 13.4%. P. multocida Serogroup A was isolated from 22 cases (95.7%), whereas serogroup F was from 1 case (4.3%). All isolates were analyzed for their susceptibility to 15 antibiotics and the presence of 18 genes for virulence factors. The susceptibility profiles suggested that Tetracycline, Cephalosporin, Enrofloxacin, and Aminoglycosides were the drugs most likely to be active against P. multocida. However, 78.3% and 52.2% of poultry strains were resistant to Penicillin and Sulfisoxazole, respectively. PCR results showed that ptfA, fimA, tonB, fur, hgbA, hgbB, sodA, sodC, pmHAS, nanH, nanB, plpB and ompH genes occur in most poultry strains of P. multocida. The virulence genes such as toxA, tadD, hsf-1, pfhA and ompA were each present in <73.9% of strains. The tonB gene was detected in all 23 clinical strains of P. multocida which were recovered from different hosts and harboring different serotypes. Phylogenetic analysis indicated that these tonB genes of P. multocida from different hosts and harboring different serotypes have close genetic relationship with a high similarity. Multiple sequence alignment demonstrated that TonB protein of Gram-negative bacteria exists in multiple conserved sites, such as -xSSGx-, -YP-, -LD-and xA[A/V]Lx motif. These findings provide clinical data into the epidemiological and molecular characteristics of avian P. multocida isolates and provide a reference for the researches of drug target in P. multocida. Keywords: Antimicrobial susceptibility, Capsular antigens, Pasteurella multocida, tonB gene, Virulence gene, Cloning, Phylogenetic analysis Çin'de Kanatlı Hayvanlardan İzole Edilen Pasteurella multocida Sışlarının Moleküler Karakterizasyonu ve tonB Geni Açısından Genetik Analizi ÖzetPasteurella multocida (P. multocida) kuşlarda kanatlı kolerasına neden olur ve hastalıkta virulans faktörleri hala tam olarak anlaşılamamıştır. TonB proteini Pasteurella da dahil pek çok Gram-negatif bakteride yaygın olarak bulunan periplazmik bir protein olup membran dışına ferrik demir komplekslerini taşımakta görevlidir ve bakterilerde besin sağlamaya yardım etmek suretiyle önemli bir virulans faktörü olarak rol oynar. Bu çalışmada, 172 klinik solunum hastalıklı ördek ve kazdan toplam 23 P. multocida izolatı elde edilerek %13.4'lük izolasyon oranı sağlandı. P. multocida Serogrup A 22 vakadan izole edilirken (%95.7), serogrup F 1 vakadan izole edildi (%4.3). Tüm izolatlar 15 antibiyotiğe kar...

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“…Receptors at the bacterial surface recognize the free heme or hemoproteins and transport heme to the periplasm. Once inside the cell, iron is released from heme (8). More elaborate heme acquisition systems secrete heme-scavenging molecules, the hemophores, which extract heme from host hemoproteins and deliver it to an outer membrane receptor for internalization (8).…”

Section: Introductionmentioning

confidence: 99%

Plasmid-Encoded Iron Uptake Systems

Lorenzo

Stork

2014

Microbiol Spectr

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Plasmids confer genetic information that benefits the bacterial cells containing them. In pathogenic bacteria, plasmids often harbor virulence determinants that enhance the pathogenicity of the bacterium. The ability to acquire iron in environments where it is limited, for instance the eukaryotic host, is a critical factor for bacterial growth. To acquire iron, bacteria have evolved specific iron uptake mechanisms. These systems are often chromosomally encoded, while those that are plasmid-encoded are rare. Two main plasmid types, ColV and pJM1, have been shown to harbor determinants that increase virulence by providing the cell with essential iron for growth. It is clear that these two plasmid groups evolved independently from each other since they do not share similarities either in the plasmid backbones or in the iron uptake systems they harbor. The siderophores aerobactin and salmochelin that are found on ColV plasmids fall in the hydroxamate and catechol group, respectively, whereas both functional groups are present in the anguibactin siderophore, the only iron uptake system found on pJM1-type plasmids. Besides siderophore-mediated iron uptake, ColV plasmids carry additional genes involved in iron metabolism. These systems include ABC transporters, hemolysins, and a hemoglobin protease. ColV-and pJM1-like plasmids have been shown to confer virulence to their bacterial host, and this trait can be completely ascribed to their encoded iron uptake systems.

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Role and regulation of heme iron acquisition in gram-negative pathogens

Cited by 103 publications

References 135 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

Çin’de Kanatlı Hayvanlardan İzole Edilen Pasteurella multocida Suşlarının Moleküler Karakterizasyonu ve tonB Geni Açısından Genetik Analizi

Plasmid-Encoded Iron Uptake Systems

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