<i>In vitro</i>
            characterization of IroB, a pathogen-associated
            <i>C</i>
            -glycosyltransferase

Fischbach, Michael A.; Lin, Hening; Liu, David R.; Walsh, Christopher T.

doi:10.1073/pnas.0408463102

Cited by 153 publications

(143 citation statements)

References 42 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…IroD was furthermore reported to catalyze regioselective hydrolysis of nonloaded mono-and diglucosylated enterobactin (191). Significantly, the linear trimeric product resulting from IroD-catalyzed monoglucosylated enterobactin hydrolysis is structurally consistent with the linearized monoglucosylated enterobactin found in posttranslationally modified microcin E492 (MccE492), and thus, a biosynthetic role of the IroD homologue MceD, which is present in the corresponding biosynthesis cluster of the natural MccE492 producer Klebsiella pneumoniae RYC492, was suggested (96,191). A later study that investigated the activities of IroD and IroE led to partially different results concerning the substrate specificities of the esterases (359).…”

Section: General Steps Of Siderophore Pathwaysmentioning

confidence: 62%

“…Homologues of IroBD and IroNE, termed MceCD and PfeAE, are also present in K. pneumoniae RYC492 and P. aeruginosa PAO1, in which they serve in posttranslational microcin modification (G. Vassiliadis, G., J. Peduzzi, S. Zirah, X. Thomas, S. Rebuffat, and D. Destoumieux-Garzon, unpublished data) and suggested exogenous siderophore utilization, respectively (95). The C-glycosyltransferase IroB was shown to function as an enterobactin-tailoring enzyme that attaches glucose moieties to the C-5 position of the enterobactin DHB moieties via an unusual C-C-bond formation (96). The glucosylated variants of enterobactin that were called salmochelins had been isolated and structurally characterized previously (22,132).…”

Section: Defense and Antidefense: Iron-related Coevolution Of Pathogementioning

confidence: 99%

See 1 more Smart Citation

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,440

1,302

View full text Add to dashboard Cite

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.

show abstract

Section: General Steps Of Siderophore Pathwaysmentioning

confidence: 62%

Section: Defense and Antidefense: Iron-related Coevolution Of Pathogementioning

confidence: 99%

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,440

1,302

View full text Add to dashboard Cite

show abstract

“…Salmochelin is a c-glucosylated form of enterobactin (332,333). This modification is carried out by genes found on either the chromosome or a plasmid within the iroA gene cluster, iroBCDE (319).…”

Section: Figmentioning

confidence: 99%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,357

1,345

View full text Add to dashboard Cite

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.

show abstract

“…Whereas most E. coli strains, including commensal strains, produce enterobactin, salmochelins, aerobactin, and yersiniabactin are associated with pathogenic E. coli strains (37,38). Salmochelins are glycosylated molecules of enterobactin that are synthesized by the iroBCDE gene products, while aerobactin is synthesized by the iucABCD gene products (39)(40)(41)(42). Interestingly, it has been reported that salmochelins and aerobactin are often associated with ExPEC strains and contribute to their virulence (38,(43)(44)(45)(46)(47)(48)(49)(50)(51).…”

mentioning

confidence: 99%

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

et al. 2014

View full text Add to dashboard Cite

eIn Escherichia coli, the small regulatory noncoding RNA (sRNA) RyhB and the global ferric uptake regulator (Fur) mediate iron acquisition and storage control. Iron is both essential and potentially toxic for most living organisms, making the precise maintenance of iron homeostasis necessary for survival. While the roles of these regulators in iron homeostasis have been well studied in a nonpathogenic E. coli strain, their impact on the production of virulence-associated factors is still unknown for a pathogenic E. coli strain. We thus investigated the roles of RyhB and Fur in iron homeostasis and virulence of the uropathogenic E. coli (UPEC) strain CFT073. In a murine model of urinary tract infection (UTI), deletion of fur alone did not attenuate virulence, whereas a ⌬ryhB mutant and a ⌬fur ⌬ryhB double mutant showed significantly reduced bladder colonization. The ⌬fur mutant was more sensitive to oxidative stress and produced more of the siderophores enterobactin, salmochelins, and aerobactin than the wild-type strain. In contrast, while RyhB was not implicated in oxidative stress resistance, the ⌬ryhB mutant produced lower levels of siderophores. This decrease was correlated with the downregulation of shiA (encoding a transporter of shikimate, a precursor of enterobactin and salmochelin biosynthesis) and iucD (involved in aerobactin biosynthesis) in this mutant grown in minimal medium or in human urine. iucD was also downregulated in bladders infected with the ⌬ryhB mutant compared to those infected with the wild-type strain. Our results thus demonstrate that the sRNA RyhB is involved in production of iron acquisition systems and colonization of the urinary tract by pathogenic E. coli.

show abstract

In vitro characterization of IroB, a pathogen-associated C -glycosyltransferase

Abstract: glycosyltransferase ͉ pathogenicity ͉ siderophore

Cited by 153 publications

References 42 publications

Siderophore-Based Iron Acquisition and Pathogen Control

Siderophore-Based Iron Acquisition and Pathogen Control

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

Contact Info

Product

Resources

About