<i>Yersinia pestis</i>IS<i>1541</i>Transposition Provides for Escape from Plague Immunity

Cornelius, Claire; Quenee, Lauriane E.; Elli, Derek; Ciletti, Nancy; Schneewind, Olaf

doi:10.1128/iai.01162-08

Cited by 22 publications

(49 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, similar to pneumonic plague in mice, F1 variants displayed a similar lethal dose in guinea pigs as the parent strain CO92. 39 Progression of pneumonic plague seemed somewhat reduced for the F1 Ϫ strains ( Figure 2C). The mean Ϯ SD time to death for Y. pestis CO92 infection was 3 Ϯ 0 days and for CO92 ⌬F1 was 4.83 Ϯ 0.37 days (P ϭ 2.1 ϫ 10 Ϫ5 ).…”

Section: Y Pestis F1 Variants Cause Pneumonic Plague In Guinea Pigsmentioning

confidence: 96%

“…Guinea pigs (cohorts of six animals) were inoculated by intranasal instillation with 5 ϫ 10 4 CFU of Y. pestis CO92, CO92 ⌬F1 (an engineered isogenic F1 Ϫ strain), 20 or Y. pestis CAC1 (a caf1A::IS1541 escape variant isolated from F1-immunized mice). 39 All the animals died of infection within 7 days ( Figure 2C). Thus, similar to pneumonic plague in mice, F1 variants displayed a similar lethal dose in guinea pigs as the parent strain CO92.…”

Section: Y Pestis F1 Variants Cause Pneumonic Plague In Guinea Pigsmentioning

confidence: 96%

“…20 The CAC1 strain harbors an insertion of the IS1541 element in the caf1A gene, which abrogates F1 pilus assembly but not pilin expression. 39 …”

Section: Bacterial Strains and Plasmidsmentioning

confidence: 99%

“…36 We compared the histopathologic findings of pneumonic plague caused by Y. pestis CO92, an F1 ϩ clinical isolate, with that precipitated by its derivative, Y. pestis CAC1 (F1 Ϫ ), a strain that carries an IS1541 insertion in the caf1A structural gene for the outer membrane usher and, therefore, cannot assemble F1 pili. 39 Lung tissues from cynomolgus macaques that died of pneumonic plague after infection with 400 CFUs of either Y. pestis CO92 or CAC1 were stained with H&E ( Figure 1). 45 Lung tissue from a macaque that died of Y. pestis CO92 infection revealed acute pneumonia.…”

Section: Pneumonic Plague In Nhps After Infection With Wild-type or Fmentioning

confidence: 99%

“…39 Because IS elements are small mobile genetic elements, we entertained the possibility that CAC1 variants may revert to an F1 ϩ phenotype under conditions when F1 is required for virulence, as occurs in the guinea pig bubonic plague model. All but one guinea pig infected by s.c. injection with Y. pestis CAC1 survived the infection ( Figure 4B).…”

Section: Y Pestis Cac1 and Lack Of F1 ϩ Reversionmentioning

confidence: 99%

See 4 more Smart Citations

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

Quenee

Ciletti

Berube

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV.

show abstract

Section: Y Pestis F1 Variants Cause Pneumonic Plague In Guinea Pigsmentioning

confidence: 96%

Section: Y Pestis F1 Variants Cause Pneumonic Plague In Guinea Pigsmentioning

confidence: 96%

“…20 The CAC1 strain harbors an insertion of the IS1541 element in the caf1A gene, which abrogates F1 pilus assembly but not pilin expression. 39 …”

Section: Bacterial Strains and Plasmidsmentioning

confidence: 99%

Section: Pneumonic Plague In Nhps After Infection With Wild-type or Fmentioning

confidence: 99%

Section: Y Pestis Cac1 and Lack Of F1 ϩ Reversionmentioning

confidence: 99%

See 3 more Smart Citations

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

Quenee

Ciletti

Berube

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

Substrates of the Plasminogen Activator Protease of Yersinia pestis

Caulfield

Lathem

2012

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Oral vaccination against plague using Yersinia pseudotuberculosis

Demeure

Derbise

Carniel

2017

Chemico-Biological Interactions

View full text Add to dashboard Cite

Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism.

show abstract

Yersinia pestisIS1541Transposition Provides for Escape from Plague Immunity

Cited by 22 publications

References 61 publications

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

Substrates of the Plasminogen Activator Protease of Yersinia pestis

Oral vaccination against plague using Yersinia pseudotuberculosis

Contact Info

Product

Resources

About