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1.
The efficacy of isepamycin vs. other aminoglycosides was studied in vitro and on albino mice with experimental plague due to natural antigen valuable strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsular antigen fraction I (FI- phenotype). The MICs of isepamycin for the strains of the plague microbe (20 FI+ and 20FI-) were 1.0-4.0 mg\l, that did not differ from those of streptomycin, kanamycin, amikacin and tobramycin. The ED50 of isepamycin in the prophylaxis and treatment of the experimental plague of the mice had no statistically significant differences from the ED50 of the other aminoglycosides. The efficacy index of isepamycin was > 10(4), that did not differ from that of streptomycin, amikacin and gentamicin, irrespective of the strain phenotype (Y. pestis 231 FI+ or Y. pestis 231 FI-). The same as the other aminoglycosides, isepamycin in doses equivalent to the human average daily doses, protected 80-100% of the albino mice from death when used in the prophylaxis and therapy of plague irrespective of the strain phenotype. The results of the study made it possible to consider isepamycin as an agent promising for the prophylaxis and treatment of plague.  相似文献   

2.
Tetracycline, doxycycline, streptomycin and rifampicin were used for prophylaxis of experimental plague in albino mice (Yersinia pestis 231, approximately 1000 LD50). The antibiotics were administered 5 hours after the infection for 5 days. Tetracycline and doxycycline provided survival of 60 to 75% of the animals, while the respective figure for streptomycin and rifampicin was 100%, but streptomycin and rifampicin inhibited development of plague immunity evident from a lower protection index (PI) by 3-4 orders. The PI for the tetracyclines lowered by 2 orders. Simultaneous prophylaxis with the tetracyclines and immunization by Y. pestis EV Rifr R(SmTc) (10(6) microbial cells) provided not only higher percentage of the animal survival (80-90%) but also development of sufficient plague immunity: PI of 1.0 x 10(5)--5.0 x 10(5). When the animals were infected with Y. pestis 231 R(SmTc) the use of the tetracyclines failed, whereas the use of doxycycline and simultaneous vaccination by EV Rifr R(SmTc) provided survival of 70-85% of the animals. Successive use of inefficient streptomycin (for 2 days) and efficient rifampicin (for 3 days) provided survival only of 30% of the mice. A similar regimen of the successive use of the inefficient and efficient antibiotics (the total term of 5 days) started simultaneously with immunization by EV Rifr R(SmTc) provided survival of 80% of the animals. The use of combined specific and urgent prophylaxis of plague infection due not only to antibiotic susceptible but also to antibiotic resistant strains of the plague pathogen was shown promising.  相似文献   

3.
Activity of aminoglycosides such as gentamicin, sisomicin and amikacin against plague microbe strains of natural origin was studied in vitro. It was also studied in prophylaxis and treatment of experimental plague infection in albino mice. The MAC of gentamicin and sisomicin for 50 strains of the plague microbe was 0.2-1.6 micrograms/ml. For the majority of the strains it was 0.4 micrograms/ml. The amikacin MICs were 0.4-3.2 and 0.8 micrograms/ml, respectively. High efficacy of gentamicin, sisomicin and amikacin was shown in prophylaxis and treatment of experimental plague infection in albino mice. The optimal doses of the antibiotics were determined. Under definite conditions such as the use of short-term regimens and higher intervals, advantages of sisomicin over gentamicin and amikacin in prophylaxis of experimental plague infection were observed.  相似文献   

4.
Mice immunization with reference vaccine at the early stage of plague infection provided animals survival and prolonged mean survival period up to 2-5 days. Ciprofloxacin, ofloxacin and pefloxacin prevents development of post vaccine immunity at white mice, immunized by reference vaccine strain EV. Nalidixic acid and norfloxacin effect on post vaccine immunity was lower. Use of immunogenic strain EV Nafr (resistant to nalidixic acid and fluoroquinolones) provided antiplague immunity formation at the background of fluoroquinolones prophylaxis. Ciprofloxacin, ofloxacin and pefloxacin used for plague prophylaxis at white mice infected with Yersinia pestis (about 1000 LD50) inhibited postinfective immunity development. Nalidixic acid and norfloxacin didn't demonstrate such effect. Urgent (fluoroquinolones) and specific (EV Nalr) combined prophylaxis was evaluated as more effective for a 5-day period and provided the development of antiplague immunity.  相似文献   

5.
Administration of highly immunogenic (ED50 12.6 mcg/mouse) F I antigen (100 mcg/mouse) to albino mice 5 hours after their contamination approximately with 1000 LD50 of Yersinia pestis 231 provided 99-percent survival of same animals (17-50%) and 2-5-day prolongation of the life-span, that was indicative of the phenomenon analogous to the survival phenomenon observed in infected animals immunized by immunogenic strains of the plague microbe. The experiment on the mice confirmed high efficacy of ceftriaxone (100-percent survival) when used prophylactically for 5 days 5 hours after the contamination by Y. pestis 231 (approximately 1000 LD50) in the dose equivalent to the daily dose for humans. However, no antiplague immunity developed in the survivors: the immunity index (II) of 1.5x10. The use of ceftriaxone according to the same scheme simultaneously with single immunization by F I antigen in a dose of 100 mcg/mouse resulted not only in 100-percent survival of the animals but also in development of expressing antiplague immunity (II 2.2x10(5)). The protection level corresponded to the control with the same live-stock of the animals after a single immunization in the analogous dose of F I antigen (II 3.2x10(4)) and the ceftriaxone use (II 1.0x10(5)), as well as after immunization of the mice by 10(6) microbial cells of Y. pestis EV NIIEG (II 1.2x10(5)). The results of the study are indicative of the prospective use of subsingle vaccines of the new generation based on F I antigen for combined specific and urgent prophylaxis.  相似文献   

6.
Tian G  Qiu Y  Qi Z  Wu X  Zhang Q  Bi Y  Yang Y  Li Y  Yang X  Xin Y  Li C  Cui B  Wang Z  Wang H  Yang R  Wang X 《PloS one》2011,6(4):e19260
In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 μg F1 and 10 μg rV270) and SV2 (200 μg F1 and 100 μg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6) CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.  相似文献   

7.
It was shown that the presence of subinhibitory concentrations of ampicillin, cefotaxime or gentamicin in the cultivation medium had a marked inhibitory effect on the catalase activity of plague microbe. The effect depended on the characteristic features of plague microbe strains and the incubation temperature. When the cells of a virulent strain of the plague microbe Y. pestis 1300 were cultivated at a temperature of 37 degrees C on a medium containing the subinhibitory concentrations of ampicillin or cefotaxime, the pathogen virulence for albino mice significantly decreased.  相似文献   

8.
The nature of increasing chromosomal resistance to quinolones was studied in a model of the plague microbe. Five virulent strains of the natural plague microbe (Y. pestis) were used in the experiment: 363 (1/1479), 231, 2385, 2442 and 2444. The one-stage procedure for isolation of the mutants was applied. It was shown that the frequency of the one-stage mutants resistant to oxalinic acid, pefloxacin and ciprofloxacin amounted to 10(-9)-10(-11) and was 2 to 3 orders of magnitude lower than that of the mutants resistant to nalidixic acid. Two types of the plague microbe mutants resistant to the quinolones were detected: those resistant to the quinolones to the generations (Nalr-phenotype) and those resistant to the representatives of the 3rd generation quinolones (Nals-phenotype). The quinolones were not efficient in the treatment of albino mice with experimental plague caused by the quinolone-resistant forms of the plague microbe.  相似文献   

9.
The modelling of glandular plague and selection of the conditions for estimating the efficacy of new antibacterials for the treatment of the infection were performed on hamadryads (baboons). The experiments showed that the average LD50 of the culture of a highly virulent strain of Yersinia pestis on its subcutaneous administration to the animals was 2089 viable microbes. In 18 per cent of the episodes the experimental glandular plague in the animals was complicated by secondary plague pneumonia. Subcutaneous administration of 2 x 10(7) viable microbial cell of the plague pathogen caused acute sepsis and the animal death. The treatment of the experimental glandular plague in the hamadryads demonstrated that new antibacterials such as amikacin, netilmicin, ceftriaxone, cefotaxime, ceftizoxime, doxycycline, rifampicin, ofloxacin and ciprofloxacin were not inferior in their efficacy to streptomycin and tetracycline successfully used in the therapy of patients with plague.  相似文献   

10.
Rapid estimation of the protective effect of antibacterial drugs on Fransiella tularensis for not more than 2 days was shown possible in experiments on albino mice infected with tularemia. High efficacy of aminoglycosides (kanamycin, gentamicin, streptomycin, amikacin, netilmicin, tobramycin, sagamycin, ribostamycin and sisomicin), tetracyclines (tetracycline, doxycycline, minocycline and methacycline), rifampicin, phosphomycin and oxolinic acid was determined with the recommended rapid method. Amoxycillin, ampicillin, piperacillin, carbenicillin, erythromycin, levomycetin, cefradine, cefmetazole, cefatrizine, cefoxitin, cefsulodin and bactrim (biseptol) proved to be inefficient against the tularemia causative agent.  相似文献   

11.
Cefotaxime was shown highly efficient in prophylaxis and treatment of experimental plague infection in albino mice. The in vitro activity of cefotaxime against natural strains of the plague microbe was 32 to 64 times higher than that of cefazolin, cephalothin and cefmetazole. The combined use of cefotaxime with amikacin significantly increased the percentage of the survived albino mice with plague infection as compared to the use of the antibiotics alone.  相似文献   

12.
A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.  相似文献   

13.
Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.  相似文献   

14.
A search for cellular components responsible for autoagglutination (AA) in broth and salt solutions of Hms- cells of the plague agent Yersinia pestis was performed. The AA- mutants were obtained using vaccine strain Y. pestis EV76 derivative containing one species-specific plasmid pYP. The mutants were shown to differ from the parent strain by the decreased surface hydrophobicity, insensitivity to plague diagnostic L-413c bacteriophage and negative haemagglutination reaction with antibodies to F1 capsular substance of the plague agent. The mutants did not differ from the parent strain by electrophoretic mobility and immunochemical activity of LPS but were characterized by the absence of a 17 kDa protein on the cell surface. The AA+ cells that lost this protein after weak alkali extraction were less hydrophobic and failed to express AA in 0.5 M ammonium sulfate. After the extraction, the cells lost the ability to neutralize L-413c and to react with the anti-F1 antibodies, while both activities as well as 17 kDa protein were detected in the extracts. Thus, the 17 kDa protein is suggested to be a hydrophobic surface antigen which acts as a receptor of the L-413c bacteriophage and represents an AA factor of Hms- cells of Y. pestis.  相似文献   

15.
F1 antigen is an attractive candidate for the development of a subunit vaccine against plague. In previous study, the extraction of this antigen from Yersinia pestis is characterized by using organic solvents. In this work, a new purification strategy that produced high-purity F1 antigen from Y. pestis EV76 was developed by the substitution of physical disruption for organic solvent one, followed by a combination of ammonium sulfate fractionation and Sephacryl S-200HR column filtration chromatography. As revealed in this study, this purification procedure is simple and effective, and avoids potential adverse effect on the antigen by organic solvents. Highly purified F1 that adsorbed to 25% (v/v) Al(OH)3 adjuvant in phosphate-buffered saline (PBS) induced very high titers of antibody to F1 in BALB/c mice and protected them (100% survival) against subcutaneous challenge with 10(4) CFU of Y. pestis virulent strain 141.  相似文献   

16.
It was demonstrated that use for prophylaxy (after 5 h of infection) or for treatment (after 24 h after infection) of the monoclonal antibodies mixture to specific epitops of capsule antigen (fraction 1), lipopolysacharide, murine toxine can prevent development of plague pathogen at 100 of mice infected by approximately 1000 LD50 Yersinia pestis 231. 5-day course of prophylaxy by monoclonal antibodies provided survival of 50 per cent animals. Subsequent use of fraction 1 antigen for 5 days followed by treatment with streptomycin or doxycycline at 6-7-8-9-10 days after infection with Y. pestis 231 prevented infection manifestation at 80 per cent of animals, etiotropic therapy started at the same period was ineffective. When white mice were infected with Y. pestis 231 Fra-, with deleted ability to produce capsule antigen (fraction 1) 80% level of efficacy can be provided by subsequent administration of antibodies to fraction 1 combinated with lipopolysacharide, murine toxine and streptomycin. Use of monoclonal antibodies followed by doxycycline was ineffective.  相似文献   

17.
目的:为研制鼠疫亚单位疫苗,克隆、表达并纯化去除产生免疫抑制作用序列后的鼠疫耶尔森氏菌LcrV抗原(rV270)。方法:依据已知的LcrV的核苷酸序列,避开其产生免疫抑制作用的区段设计引物,扩增rV270基因并克隆到pET24a载体中,在大肠杆菌BL21中表达His-rV270融合蛋白:表达产物先后经Co^2+亲和层析和Sephacryl S-200HR凝胶柱纯化,并在纯化过程中应用凝血酶切除His标塔;氢氧化铝佐剂吸附重组抗原后免疫BALB/c小鼠,初次免疫后第21天加强免疫1次,第5周使用104CFU鼠疫菌141强毒株攻毒,测定其免疫保护作用。结果:rV270以可溶性方式表达;应用Co^2+亲和层析柱和Sephacryl S-200HR凝胶柱结合凝血蛋白酶切除His标签的方法可得到不含标签的较高纯度的重组蛋白;攻毒实验中实验组小鼠全部存活,而对照组全部死亡。结论:获得了具有良好免疫保护作用的rV270蛋白,可用于鼠疫亚单位疫苗的研究。  相似文献   

18.
The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.  相似文献   

19.
Mono- and polyresistant variants of the plague vaccinal strain Yersinia pestis EV76 (RIEG line) were constructed with stage-by-stage transduction of transposons Tn5, T, Tn10 and Tn9 located in the phage vectors. Methods for stage-by-stage selection of the transductants that preserved intact determinants of surviving, antiphagocytic activity and immunogenic properties were designed for their further testing as model vaccinal strains in combined specific and emergent medicamentous prophylaxis of plague.  相似文献   

20.
Possible use of ciprofloxacin combinations with some other antibiotics such as rifampicin, ampicillin, cefotaxime, doxycycline and amikacin was studied on albino mice with experimental plague caused by the pathogen strain (approximately 1000 LD50) deprived of the ability to produce the capsular antigen, fraction I (Fra- phenotype). The combination of ciprofloxacin with ampicillin or doxycycline had no effect on the increase of the survival rate (t<2) evident of inexpediency of its use in the infection caused by the Fra- strains of the plague microbe. The combination of ciprofloxacin and cefotaxime used in definite doses had some effect (t=2.6). The most significant synergistic effect was observed with the use of ciprofloxacin in combination with amikacin or rifampicin (t>3.3-9.0) which made the combination most promising.  相似文献   

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