yersiniabactin and Sepsis

yersiniabactin has been researched along with Sepsis* in 4 studies

Other Studies

4 other study(ies) available for yersiniabactin and Sepsis

ArticleYear
Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study.
    PLoS genetics, 2020, Volume: 16, Issue:10

    The genus Escherichia is composed of several species and cryptic clades, including E. coli, which behaves as a vertebrate gut commensal, but also as an opportunistic pathogen involved in both diarrheic and extra-intestinal diseases. To characterize the genetic determinants of extra-intestinal virulence within the genus, we carried out an unbiased genome-wide association study (GWAS) on 370 commensal, pathogenic and environmental strains representative of the Escherichia genus phylogenetic diversity and including E. albertii (n = 7), E. fergusonii (n = 5), Escherichia clades (n = 32) and E. coli (n = 326), tested in a mouse model of sepsis. We found that the presence of the high-pathogenicity island (HPI), a ~35 kbp gene island encoding the yersiniabactin siderophore, is highly associated with death in mice, surpassing other associated genetic factors also related to iron uptake, such as the aerobactin and the sitABCD operons. We confirmed the association in vivo by deleting key genes of the HPI in E. coli strains in two phylogenetic backgrounds. We then searched for correlations between virulence, iron capture systems and in vitro growth in a subset of E. coli strains (N = 186) previously phenotyped across growth conditions, including antibiotics and other chemical and physical stressors. We found that virulence and iron capture systems are positively correlated with growth in the presence of numerous antibiotics, probably due to co-selection of virulence and resistance. We also found negative correlations between virulence, iron uptake systems and growth in the presence of specific antibiotics (i.e. cefsulodin and tobramycin), which hints at potential "collateral sensitivities" associated with intrinsic virulence. This study points to the major role of iron capture systems in the extra-intestinal virulence of the genus Escherichia.

    Topics: Animals; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Genetic Variation; Genome-Wide Association Study; Genomic Islands; Humans; Iron; Mice; Phenols; Phylogeny; Sepsis; Siderophores; Thiazoles; Virulence

2020
Contribution of yersiniabactin to the virulence of an Escherichia coli sequence type 69 ("clonal group A") cystitis isolate in murine models of urinary tract infection and sepsis.
    Microbial pathogenesis, 2018, Volume: 120

    Escherichia coli sequence type 69 (ST69; "clonal group A") is an important extraintestinal pathogen. To clarify the yersiniabactin siderophore system's role in ST69's extraintestinal virulence we compared a wild-type ST69 cystitis isolate, isogenic irp2 (yersiniabactin) mutants, and irp2-complemented mutants in murine models of sepsis and urinary tract infection (UTI). irp2 mutants were attenuated mildly in the UTI model and profoundly in the sepsis model. In both models, complementation with a functional copy of irp2 restored full parental virulence. These findings suggest that in ST69 the yersiniabactin system has a minor role in urovirulence and a major role in sepsis causation.

    Topics: Animals; Cystitis; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Gene Deletion; Genetic Complementation Test; Iron Regulatory Protein 2; Mice; Mutation; Phenols; Sepsis; Thiazoles; Urinary Tract Infections; Virulence; Virulence Factors

2018
The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice.
    Molecular microbiology, 2014, Volume: 93, Issue:4

    Bacterial pathogens must overcome host sequestration of zinc (Zn(2+) ), an essential micronutrient, during the infectious disease process. While the mechanisms to acquire chelated Zn(2+) by bacteria are largely undefined, many pathogens rely upon the ZnuABC family of ABC transporters. Here we show that in Yersinia pestis, irp2, a gene encoding the synthetase (HMWP2) for the siderophore yersiniabactin (Ybt) is required for growth under Zn(2+) -deficient conditions in a strain lacking ZnuABC. Moreover, growth stimulation with exogenous, purified apo-Ybt provides evidence that Ybt may serve as a zincophore for Zn(2+) acquisition. Studies with the Zn(2+) -dependent transcriptional reporter znuA::lacZ indicate that the ability to synthesize Ybt affects the levels of intracellular Zn(2+) . However, the outer membrane receptor Psn and TonB as well as the inner membrane (IM) ABC transporter YbtPQ, which are required for Fe(3+) acquisition by Ybt, are not needed for Ybt-dependent Zn(2+) uptake. In contrast, the predicted IM protein YbtX, a member of the Major Facilitator Superfamily, was essential for Ybt-dependent Zn(2+) uptake. Finally, we show that the ZnuABC system and the Ybt synthetase HMWP2, presumably by Ybt synthesis, both contribute to the development of a lethal infection in a septicaemic plague mouse model.

    Topics: Animals; ATP-Binding Cassette Transporters; Disease Models, Animal; Mice; Phenols; Plague; Sepsis; Thiazoles; Virulence; Virulence Factors; Yersinia pestis; Zinc

2014
Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli.
    PLoS pathogens, 2013, Volume: 9, Issue:7

    In Escherichia coli, the biosynthetic pathways of several small iron-scavenging molecules known as siderophores (enterobactin, salmochelins and yersiniabactin) and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl transferase (PPTase). Only two PPTases have been clearly identified: EntD and ClbA. The gene coding for EntD is part of the core genome of E. coli, whereas ClbA is encoded on the pks pathogenicity island which codes for colibactin. Interestingly, the pks island is physically associated with the high pathogenicity island (HPI) in a subset of highly virulent E. coli strains. The HPI carries the gene cluster required for yersiniabactin synthesis except for a gene coding its cognate PPTase. Here we investigated a potential interplay between the synthesis pathways leading to the production of siderophores and colibactin, through a functional interchangeability between EntD and ClbA. We demonstrated that ClbA could contribute to siderophores synthesis. Inactivation of both entD and clbA abolished the virulence of extra-intestinal pathogenic E. coli (ExPEC) in a mouse sepsis model, and the presence of either functional EntD or ClbA was required for the survival of ExPEC in vivo. This is the first report demonstrating a connection between multiple phosphopantetheinyl-requiring pathways leading to the biosynthesis of functionally distinct secondary metabolites in a given microorganism. Therefore, we hypothesize that the strict association of the pks island with HPI has been selected in highly virulent E. coli because ClbA is a promiscuous PPTase that can contribute to the synthesis of both the genotoxin and siderophores. The data highlight the complex regulatory interaction of various virulence features with different functions. The identification of key points of these networks is not only essential to the understanding of ExPEC virulence but also an attractive and promising target for the development of anti-virulence therapy strategies.

    Topics: Animals; Bacterial Proteins; Enterobactin; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Gene Deletion; Genomic Islands; Glycopeptides; Isoenzymes; Mice; Mice, Inbred C57BL; Mutagens; Mutation; Peptides; Phenols; Polyketides; Sepsis; Siderophores; Thiazoles; Transferases (Other Substituted Phosphate Groups); Virulence

2013