First multi-epitope subunit vaccine against extraintestinal pathogenic Escherichia coli delivered by a bacterial type-3 secretion system (T3SS)

Wieser, Andreas; Magistro, Giuseppe; Nörenberg, Dominik; Hoffmann, Christiane; Schubert, Sören

doi:10.1016/j.ijmm.2011.09.012

Cited by 32 publications

(28 citation statements)

References 38 publications

(45 reference statements)

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“…Similar results were obtained when the multiepitope vaccines were administered via a live bacterial antigen delivery system based on the Salmonella type 3 secretion system [112]. In agreement with earlier results, immunization with the Vol1 (pST1) construct significantly reduced bacterial loads in the murine liver and spleen, in contrast to the Vol2 (pST2), which did not induce significant protection [112]. These data from the multiepitope and iron receptor-based immunization studies are encouraging for UTI vaccine development and continued research into UPEC iron acquisition during infection may help inform future vaccine designs that target UPEC, as well as other pathogens that depend on iron acquisition to survive within the host.…”

Section: Required For Growth In the Host: Iron Acquisition System-bassupporting

confidence: 72%

“…However, only immunization with the Vol1 construct, containing domains from FyuA, IutA, Iha and Usp, was able to significantly decrease experimental UPEC bacterial loads in the spleen [111]. Similar results were obtained when the multiepitope vaccines were administered via a live bacterial antigen delivery system based on the Salmonella type 3 secretion system [112]. In agreement with earlier results, immunization with the Vol1 (pST1) construct significantly reduced bacterial loads in the murine liver and spleen, in contrast to the Vol2 (pST2), which did not induce significant protection [112].…”

Section: Required For Growth In the Host: Iron Acquisition System-basmentioning

confidence: 83%

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Preventing urinary tract infection: progress toward an effectiveEscherichia colivaccine

Brumbaugh

Mobley²

2012

Expert Review of Vaccines

175

116

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Uncomplicated urinary tract infections (UTIs) are common, with nearly half of all women experiencing at least one UTI in their lifetime. This high frequency of infection results in huge annual economic costs, decreased workforce productivity and high patient morbidity. At least 80% of these infections are caused by uropathogenic Escherichia coli (UPEC). UPEC can reside side by side with commensal strains in the gastrointestinal tract and gain access to the bladder via colonization of the urethra. Antibiotics represent the current standard treatment for UTI; however, even after treatment, patients frequently suffer from recurrent infection with the same or different strains. In addition, successful long-term treatment has been complicated by a rise in both the number of antibiotic-resistant strains and the prevalence of antibiotic-resistance mechanisms. As a result, preventative approaches to UTI, such as vaccination, have been sought. This review summarizes recent advances in UPEC vaccine development and outlines future directions for the field.

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Section: Required For Growth In the Host: Iron Acquisition System-bassupporting

confidence: 72%

Section: Required For Growth In the Host: Iron Acquisition System-basmentioning

confidence: 83%

Preventing urinary tract infection: progress toward an effectiveEscherichia colivaccine

Brumbaugh

Mobley²

2012

Expert Review of Vaccines

175

116

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“…NlpI's evasion of serum-mediated killing is through regulation of the complement regulator C4bp deposition on the bacterial surface (53). Studies are in progress to determine the broadly conserved antigens or a multi-epitope subunit vaccine for the prevention of E. coli bacteremia and subsequent meningitis (50, 51, 54). …”

Section: E Coli Penetration Of the Blood-brain Barriermentioning

confidence: 99%

Human Meningitis-Associated Escherichia coli

Kim

2016

EcoSal Plus

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E. coli is the most common Gram-negative bacillary organism causing meningitis and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high-degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essentials step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high-degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high-degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis.

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“…for protection against Shigella [13], and for new antibacterial drugs [14]. They have also been used to deliver vaccine antigens to the cytosol of eukaryotic cells [15], [16]. NF-T3SSs have been most thoroughly studied for their role in antagonistic associations between pathogens and their hosts, but they also play an important role in mutualistic associations between bacteria and insects [17], plants [18], or fungi [19].…”

Section: Introductionmentioning

confidence: 99%

The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems

2012

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Type 3 secretion systems (T3SSs) are essential components of two complex bacterial machineries: the flagellum, which drives cell motility, and the non-flagellar T3SS (NF-T3SS), which delivers effectors into eukaryotic cells. Yet the origin, specialization, and diversification of these machineries remained unclear. We developed computational tools to identify homologous components of the two systems and to discriminate between them. Our analysis of >1,000 genomes identified 921 T3SSs, including 222 NF-T3SSs. Phylogenomic and comparative analyses of these systems argue that the NF-T3SS arose from an exaptation of the flagellum, i.e. the recruitment of part of the flagellum structure for the evolution of the new protein delivery function. This reconstructed chronology of the exaptation process proceeded in at least two steps. An intermediate ancestral form of NF-T3SS, whose descendants still exist in Myxococcales, lacked elements that are essential for motility and included a subset of NF-T3SS features. We argue that this ancestral version was involved in protein translocation. A second major step in the evolution of NF-T3SSs occurred via recruitment of secretins to the NF-T3SS, an event that occurred at least three times from different systems. In rhizobiales, a partial homologous gene replacement of the secretin resulted in two genes of complementary function. Acquisition of a secretin was followed by the rapid adaptation of the resulting NF-T3SSs to multiple, distinct eukaryotic cell envelopes where they became key in parasitic and mutualistic associations between prokaryotes and eukaryotes. Our work elucidates major steps of the evolutionary scenario leading to extant NF-T3SSs. It demonstrates how molecular evolution can convert one complex molecular machine into a second, equally complex machine by successive deletions, innovations, and recruitment from other molecular systems.

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First multi-epitope subunit vaccine against extraintestinal pathogenic Escherichia coli delivered by a bacterial type-3 secretion system (T3SS)

Cited by 32 publications

References 38 publications

Preventing urinary tract infection: progress toward an effectiveEscherichia colivaccine

Preventing urinary tract infection: progress toward an effectiveEscherichia colivaccine

Human Meningitis-Associated Escherichia coli

The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems

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