Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge

Abstract

We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131–326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague.

Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection

“…Furthermore, we demonstrate that genes encoding bacterial systems for iron acquisition, including the yersiniabactin system, are highly expressed during natural, uncomplicated cystitis in women. Overall, our data support the yersiniabactin system as a therapeutic target to prevent or treat UPEC-mediated UTI and reinforce the potential of the yersiniabactin system as a common target for several, increasingly multidrug-resistant, Gram-negative enteric pathogens (38,39).…”

LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

“…The coated plates were incubated overnight at 4°C. The procedures for measuring antibody titer were described in our previous report (65). Absorbance readings that were 0.1 higher than PBS control values were considered to represent a positive result.…”

Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague

“…Escherichia coli and S. Typhimurium UK-1 strains were routinely cultured at 37°C in LB broth [19] or on LB agar. S. Typhimurium UK-1 mutant strains were supplemented with 50 μg/ml of Diaminopimelic acid (DAP), 0.05% arabinose or 0.1% mannose when necessary for bacterial growth as described in our previous work [12]. Carbohydrate-free nutrient broth (NB) was used for growth when determining LPS profiles.…”

“…We found that recombinant attenuated Salmonella vaccine (RASV) strains synthesizing LcrV196 or Psn individually protected mice against subcutaneous (s.c.) or intranasal (i.n.) challenge with Y. pestis CO92 [12]. Also, immunization with a RASV delivering YadC induced partial protection in mice against bubonic plague, but not pneumonic plague [13].…”