Yersiniabactin from Yersinia pestis: biochemical characterization of the siderophore and its role in iron transport and regulation

Perry, Robert D.; Balbo, Paul; Jones, Heather; Fetherston, Jacqueline D.; DeMoll, Edward

doi:10.1099/13500872-145-5-1181

Cited by 152 publications

(143 citation statements)

References 16 publications

(37 reference statements)

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“…The majority of infectious E. coli strains possess multiple systems for ferric ion uptake, notably the relatively lowaffinity aerobactin system and the two high-affinity systems yersiniabactin and enterobactin (Braun, 2003;Perry et al, 1999;Schubert et al, 1998). Our data support the notion that iron-limiting conditions affect biofilm-dwelling E. coli more than their planktonic counterparts.…”

Section: Discussionmentioning

confidence: 99%

The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine

2008

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Urinary tract infection (UTI) is the most common infection in patients with indwelling urinary catheters, and bacterial biofilm formation is a major problem in this type of infection. Escherichia coli is responsible for the large majority of UTIs. Free iron is strictly limited in the human urinary tract and there is fierce competition between the host and infectious bacteria for this essential metal. Urinary tract infectious E. coli have highly efficient mechanisms of iron acquisition, one of which is the yersiniabactin system. The fyuA gene, encoding the yersiniabactin receptor, is one of the most upregulated genes in biofilm; it was upregulated 63-fold in the E. coli UTI strain VR50. FyuA was found to be highly important for biofilm formation in iron-poor environments such as human urine. Mutants in fyuA show aberrant biofilm formation and the cells become filamentous; a VR50fyuA mutant showed a 92 % reduction in biofilm formation in urine flow-cell chambers compared with the wild-type. The FyuA/yersiniabactin system is known to be important for virulence. Here we demonstrate a direct link between FyuA and biofilm formation in iron-poor environments. We also show that the availability of iron greatly influences UTI strains' ability to form biofilm. INTRODUCTIONIron is essential for bacterial growth. Bacteria face ironlimiting conditions in the mammalian host, where free iron is strictly limited and iron is normally bound to sequestering proteins such as transferrin and lactoferrin. To counter such iron-limiting conditions bacteria use different highly efficient mechanisms of iron acquisition. A typical high-affinity iron-uptake system consists of a lowmolecular-mass Fe 3+ -chelating compound, known as a siderophore, combined with its cognate membrane-located receptor (Martinez et al., 1990). Such iron-acquisition systems are generally regarded as important virulence or fitness factors. A range of enterobacteria contain a gene cluster called the high-pathogenicity island (HPI) encoding proteins for biosynthesis of the yersiniabactin (Ybt) siderophore and its uptake system (Rakin et al., 1999;Schubert et al., 1998Schubert et al., , 2004. The HPI is widespread among members of the Enterobacteriaceae and is essential for virulence in Yersinia and certain pathotypes of Escherichia coli (Schubert et al., 2004). One of the important genes residing on the HPI is fyuA, encoding the 71 kDa outer-membrane protein FyuA (ferric yersiniabactin uptake), which act as a receptor for Fe-Ybt siderophore uptake (Heesemann et al., 1993;Rakin et al., 1994;Schubert et al., 2002). The fyuA gene has been associated with virulence in many members of the Enterobacteriaceae (Schubert et al., , 2002.Urinary tract infection (UTI) is a serious health problem that affects millions of people each year (Stamm & Norrby, 2001). The recurrence rate is high, and often the infections are particularly troublesome and become chronic with multiple episodes. UTI usually starts as a bladder infection but often ascends to affect the kidneys and ultimatel...

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Section: Discussionmentioning

confidence: 99%

The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine

2008

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“…It was found that YbtA binds, possibly as a dimer, to its promoter target sequences independent of yersiniabactin (10). However, as transcriptional activation is yersiniabactin dependent (249), the interaction of the YbtA-DNA complex with Fe-yersiniabactin was proposed to be a prerequisite for the recruitment of the RNA polymerase complex (9). IrgB, in contrast, is a LysR family-type regulator acting as a transcriptional activator of the Vibrio cholerae IrgA Fe-enterobactin receptor (118).…”

Section: Gene Regulation Of Microbial Iron Homeostasismentioning

confidence: 99%

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,416

1,302

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SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

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“…Several siderophores are expressed in K. pneumoniae, including enterobactin, yersiniabactin, salmochelin, and aerobactin, and the roles of these different siderophore molecules in K. pneumoniae infection are discussed in detail below. The affinity of these siderophores for iron ranges from aerobactin with the lowest to enterobactin with the highest (313,314).…”

Section: Siderophoresmentioning

confidence: 99%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,302

1,345

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SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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Yersiniabactin from Yersinia pestis: biochemical characterization of the siderophore and its role in iron transport and regulation

Cited by 152 publications

References 16 publications

The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine

The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine

Siderophore-Based Iron Acquisition and Pathogen Control

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

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