Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR

Létoffé, Sylvie; Nato, Faridabano; Goldberg, Michel; Wandersman, Cécile

doi:10.1046/j.1365-2958.1999.01499.x

Cited by 98 publications

(83 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E. coli C600⌬hemA::kan and pFR2 were gifts from C. Wandersman. pFR2 contains the hasR gene of Serratia marcescens, which can be expressed in E. coli upon induction with 0.02% arabinose (22). The EC28⌬hemA mutant was constructed by P1 transduction (23) of the E. coli strain C600⌬hemA::kan by selection for kanamycin resistance, followed by testing the requirement of ␦-aminolevulinic acid on minimal medium containing glycerol as a nonfermentable C-source (24).…”

Section: Methodsmentioning

confidence: 99%

Physical Interaction of CcmC with Heme and the Heme Chaperone CcmE during Cytochrome c Maturation

Ren

Thöny‐Meyer

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Biogenesis of c-type cytochromes requires the covalent attachment of heme to the apoprotein. In Escherichia coli, this process involves eight membrane proteins encoded by the ccmABCDEFGH operon. CcmE binds heme covalently and transfers it to apocytochromes c in the presence of other Ccm proteins. CcmC is necessary and sufficient to incorporate heme into CcmE. Here, we report that the CcmC protein directly interacts with heme. We further show that CcmC coimmunoprecipitates with CcmE. CcmC contains two conserved histidines and a signature sequence, the socalled tryptophan-rich motif, which is the only element common to cytochrome c maturation proteins of bacteria, archae, plant mitochondria, and chloroplasts. We report that mutational changes of these motifs affecting the function of CcmC in cytochrome c maturation do not influence heme binding of CcmC. However, the mutants are defective in the CcmC-CcmE interaction, suggesting that these motifs are involved in the formation of a CcmC-CcmE complex. We propose that CcmC, CcmE, and heme interact directly with each other, establishing a periplasmic heme delivery pathway for cytochrome c maturation.

show abstract

Section: Methodsmentioning

confidence: 99%

Physical Interaction of CcmC with Heme and the Heme Chaperone CcmE during Cytochrome c Maturation

Ren

Thöny‐Meyer

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Either TonB or the TonB homolog HasB provides the energy necessary for transporting heme from the surface-exposed HasR-HasA-heme complex into the periplasm (83). HasR can also bind free heme and hemoglobin-bound heme, but these processes are less efficient than HasA-mediated heme acquisition (33,57). The HxuA system has been described only for Haemophilus influenzae type b (Hib) and consists of the hxuCBA gene cluster (19).…”

Section: Heme Sources Exploited By Bacterial Pathogensmentioning

confidence: 99%

Overcoming the Heme Paradox: Heme Toxicity and Tolerance in Bacterial Pathogens

2010

View full text Add to dashboard Cite

Virtually all bacterial pathogens require iron to infect vertebrates. The most abundant source of iron within vertebrates is in the form of heme as a cofactor of hemoproteins. Many bacterial pathogens have elegant systems dedicated to the acquisition of heme from host hemoproteins. Once internalized, heme is either degraded to release free iron or used intact as a cofactor in catalases, cytochromes, and other bacterial hemoproteins. Paradoxically, the high redox potential of heme makes it a liability, as heme is toxic at high concentrations. Although a variety of mechanisms have been proposed to explain heme toxicity, the mechanisms by which heme kills bacteria are not well understood. Nonetheless, bacteria employ various strategies to protect against and eliminate heme toxicity. Factors involved in heme acquisition and detoxification have been found to contribute to virulence, underscoring the physiological relevance of heme stress during pathogenesis. Herein we describe the current understanding of the mechanisms of heme toxicity and how bacterial pathogens overcome the heme paradox during infection.

show abstract

“…Several bacterial pathogens, including P. shigelloides (9), obtain iron from heme or heme-containing compounds. Heme iron utilization systems have been examined in many gram-negative pathogens, including Vibrio cholerae (20,21,38), Vibrio vulnificus (30), Shigella dysenteriae (37,60), Escherichia coli O157:H7 (54), Serratia marcescens (16,26,27), yersiniae (22,50,51,53), Haemophilus (8,11,24,32), neisseriae (7,29,52,64), Pseudomonas (23,28,39), and Porphyromonas gingivalis (47). Many heme iron utilization systems studied to date require an outer membrane receptor which binds heme from the environment (for a review, see reference 58).…”

mentioning

confidence: 99%

Characterization of the Plesiomonas shigelloides Genes Encoding the Heme Iron Utilization System

et al. 2001

View full text Add to dashboard Cite

Plesiomonas shigelloides is a gram-negative pathogen which can utilize heme as an iron source. In previous work, P. shigelloides genes which permitted heme iron utilization in a laboratory strain of Escherichia coli were isolated. In the present study, the cloned P. shigelloides sequences were found to encode ten potential heme utilization proteins: HugA, the putative heme receptor; TonB and ExbBD; HugB, the putative periplasmic binding protein; HugCD, the putative inner membrane permease; and the proteins HugW, HugX, and HugZ. Three of the genes, hugA, hugZ, and tonB, contain a Fur box in their putative promoters, indicating that the genes may be iron regulated. When the P. shigelloides genes were tested in E. coli K-12 or in a heme iron utilization mutant of P. shigelloides, hugA, the TonB system genes, and hugW, hugX, or hugZ were required for heme iron utilization. When the genes were tested in a hemA entB mutant of E. coli, hugWXZ were not required for utilization of heme as a porphyrin source, but their absence resulted in heme toxicity when the strains were grown in media containing heme as an iron source. hugA could replace the Vibrio cholerae hutA in a heme iron utilization assay, and V. cholerae hutA could complement a P. shigelloides heme utilization mutant, suggesting that HugA is the heme receptor. Our analyses of the TonB system of P. shigelloides indicated that it could function in tonB mutants of both E. coli and V. cholerae and that it was similar to the V. cholerae TonB1 system in the amino acid sequence of the proteins and in the ability of the system to function in high-salt medium.Plesiomonas shigelloides is a gram-negative bacterium associated with diarrheal disease in humans (4). The organism has been reported to cause several types of gastroenteritis, including acute secretory gastroenteritis (33), an invasive shigellosislike disease (35), and a cholera-like illness (55). Extraintestinal infections, such as meningitis, bacteremia (2), and pseudoappendicitis (13), are also associated with P. shigelloides infection.Many bacterial pathogens have iron transport systems that play a critical role in allowing the organism to establish an infection (for reviews, see references 31 and 41). Several bacterial pathogens, including P. shigelloides (9), obtain iron from heme or heme-containing compounds. Heme iron utilization systems have been examined in many gram-negative pathogens, including Vibrio cholerae (20,21,38), Vibrio vulnificus (30), Shigella dysenteriae (37, 60), Escherichia coli O157:H7 (54), Serratia marcescens (16, 26, 27), yersiniae (22, 50, 51, 53), Haemophilus (8,11,24,32), neisseriae (7,29,52,64), Pseudomonas (23,28,39), and Porphyromonas gingivalis (47). Many heme iron utilization systems studied to date require an outer membrane receptor which binds heme from the environment (for a review, see reference 58). TonB, with the aid of ExbBD, is thought to interact with the receptor to allow movement of heme into the periplasm. A periplasmic binding protein then moves the heme across th...

show abstract

Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR

Cited by 98 publications

References 32 publications

Physical Interaction of CcmC with Heme and the Heme Chaperone CcmE during Cytochrome c Maturation

Physical Interaction of CcmC with Heme and the Heme Chaperone CcmE during Cytochrome c Maturation

Overcoming the Heme Paradox: Heme Toxicity and Tolerance in Bacterial Pathogens

Characterization of the Plesiomonas shigelloides Genes Encoding the Heme Iron Utilization System

Contact Info

Product

Resources

About