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Attenuating bacterial virulence by attenuating bacterial folate transport

A technology of bacteria and folic acid, applied in the direction of antibacterial drugs, bacterial antigen components, antibody medical components, etc., can solve the problem of no cross-protection vaccines

Pending Publication Date: 2019-12-17
BOEHRINGER INGELHEIM VETMEDICA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Considerable research has been done to find suitable vaccine candidates, however, no cross-protective vaccine is currently available

Method used

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  • Attenuating bacterial virulence by attenuating bacterial folate transport
  • Attenuating bacterial virulence by attenuating bacterial folate transport
  • Attenuating bacterial virulence by attenuating bacterial folate transport

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Supplement of embodiment 1 Streptococcus suis bacterial strain S735

[0036] S735 was supplemented with plasmid pCOM1 containing one of the two ORFs in the V[10] operon (i.e. orf2[10] or folC[10]) previously the putative promoter region of the operon from strain 10, or with Plasmid pCOM1 (orf2[S735]) of orf2 of bacterial strain S735 and homologous upstream promoter ( figure 1 ). To construct these plasmids, primers with restriction sites were designed to amplify the promoter regions of orf2[10] or orf2[S735](comE1–comE2), folC[10](comE4–comE6) or operons ( comE1–comE3) (Table 1). The resulting PCR products orf2[10] and orf2[S735] were digested with restriction enzymes SacI and BamHI, cloned into pKUN19[15], digested with the same restriction enzymes, and subsequently cloned into pCOM1 to obtain pCOM1- orf2[10] and pCOM1-orf2[S735]. The PCR amplicon of folC[10] was digested with restriction enzymes SmaI and BamHI and cloned into pKUN19 cut with the same restriction e...

Embodiment 2

[0037] Example 2 Experimental Infection with Supplementary Isolates

[0038] Experimental infection of sterile piglets obtained by caesarean section was performed as previously described [14]. Prior to infection, piglet sterility was confirmed by plating tonsil swabs on Columbia agar plates containing 6% horse blood. Briefly, 4 or 5 week-old sterile pigs were treated with 10 6 Colony forming units (CFU) of Streptococcus suis for intravenous infection followed immediately by oral administration of 40 mg kg twice daily -1 Body weight of erythromycin (erythromycin-stearate, Abbott B.V., Amstelveen, The Netherlands) to maintain selection pressure on S. suis isolates carrying the pCOM plasmid. Infected pigs were monitored twice daily for clinical signs and tonsil swabs were collected for bacteriological analysis. Euthanize pigs when clinical body weights of arthritis, meningitis, or sepsis are observed after infection with S. suis. Tissue samples of the CNS, serosae and joints ...

Embodiment 3

[0041] Example 3 Experimental infection with strain 10ΔfolT (CBS 140425), experiment 1

[0042] Ten 4-week-old piglets were housed in two groups of five animals at the CVI animal facility. Piglets have free access to feed and fresh water. Animals were provided with warm lights and play materials throughout the experiment. Tonsil swabs from piglets were screened for colonization with S. suis serotype 2 by PCR before the start of the experiment. Only PCR-negative piglets were included in the experiment. After ten days, in the jugular vein with 1,1x10 6 CFU wild type strain 10 or 9.2x10 5 CFU mutant 10ΔfolT infected animals intravenously. The basal temperature of the piglets was monitored daily for a period of three days prior to infection. EDTA blood was collected prior to infection to obtain pre-infection plasma samples, as well as basal levels of white blood cell (WBC) numbers. Infected pigs were monitored for clinical signs three times daily at 8pm, 3am and 9am. Nonsp...

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Abstract

The invention relates to bacterial infections, vaccines directed against those infections and bacterial vaccines. More particularly, the invention relates to vaccines directed against Streptococcus infections in pigs. Provided is a [Delta]FolT mutant of a bacterium having reduced capacity to transport folate, wherein the capacity has been reduced by functionally deleting folate transporter (FolT)function. The present invention provides a method to reduce virulence of a bacterium comprising reducing the capacity of the bacterium to transport folate.

Description

technical field [0001] The present invention relates to bacterial strains, drugs against bacterial infections and bacterial vaccines. More specifically, the present invention relates to vaccines against Streptococcus infections in pigs. Background technique [0002] Plants, fungi, some protists and most bacteria make folic acid (vitamin B9) de novo starting from GTP and chorismate, but higher animals lack key enzymes of the synthetic pathway and thus require dietary folic acid. Folate is essential to health, and antifolate drugs are widely used in cancer chemotherapy and antimicrobials. For these reasons, folate synthesis and salvage pathways have been extensively characterized in model organisms, and folate synthesis pathways in both bacteria and plants have been engineered in order to increase the folate content of foods. Tetrahydrofolate is an essential cofactor for many biosynthetic enzymes. It acts as a carrier of one-carbon units in the synthesis of such key metabol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/09C12R1/46A61K39/00
CPCA61K39/092A61K2039/522A61K2039/552A61P31/04C07K14/315C12R2001/46C12N1/205A61K2039/542
Inventor A·英格布里森A·纽鲍尔H·E·史密斯A·德格雷夫
Owner BOEHRINGER INGELHEIM VETMEDICA GMBH
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