Construction and evaluation of DNA vaccines encoding Edwardsiella tarda antigens

Edwardsiella tarda is an opportunistic pathogen that can infect humans, animal, and fish. Two E. tarda antigens, Eta6 and FliC, which are homologues to an ecotin precursor and the FliC flagellin, respectively, were identified by in vivo-induced antigen technology from a pathogenic E. tarda strain isolated from diseased fish. When used as a subunit vaccine, purified recombinant Eta6 was moderately protective against lethal challenge of E. tarda in a Japanese flounder model, whereas purified recombinant FliC showed no apparent immunoprotectivity. Similarly, DNA vaccines based on eta6 and fliC in the form of plasmids pEta6 and pFliC induced, respectively, moderate and marginal protection against E. tarda infection. To improve the vaccine efficacy of eta6, a chimeric DNA vaccine, pCE6, was constructed, which encodes Eta6 fused in-frame to FliC. pCE6 was found to induce significantly higher level of protection than pEta6. Likewise, another chimeric DNA vaccine, pCE18, which expresses FliC fused to a previously identified E. tarda antigen Et18, elicited significantly stronger protective immunity than the DNA vaccine based on et18 alone. Fish immunized with pEta6 and pCE6 produced specific serum antibodies and exhibited significantly enhanced expression of the genes encoding elements that are involved in both innate and adaptive immune responses. Furthermore, the induction magnitudes of most of these genes were significantly higher in pCE6-vaccinated fish than in pEta6-vaccinated fish.     

Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West Africa

The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium falciparum was explored in samples from patients with uncomplicated malaria and tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation. This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 geometric mean (GMIC50) values, while those carrying both Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage disequilibrium with an excess of MM and WW and a deficit of single mutants (MW and WM), suggesting that parasite fitness is higher for the former and lower for the latter.     

Protective efficacy of two new anti-caries DNA vaccines

As we know, the catalytic region of glucosyltransferases (GTFs) is a key region responsible for sucrose-dependent adherence of cariogenic bacteria to teeth. In this study, we evaluate the potential of the catalytic region to enhance the immunogenicity of the anti-caries DNA vaccine. We construct two new anti-caries DNA plasmids pGJGAC/VAX and pGJGA-5C/VAX by cloning different styles of the catalytic regions of GTFs into the previous plasmid pGJA-P/VAX. One is the 1.1 kb full length catalytic region of S. sobrinus GTF-I, the other is its catalytic core sequence which is conserved in the GTFs from mutans streptococci and plays a central role in the enzymatic activities of sucrose splitting and glucan synthesis. The results of caries protection experiment indicate that compared to pGJA-P/VAX, immunization with both new plasmids provides more effective protection against cariogenic bacteria, especially against S. sobrinus. The plasmid encoding full length catalytic region could provide more effective protection against cariogenic bacteria than that encoding catalytic core conserved sequence even though the differences are not very dramatic.     

Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection

Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T. cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8⁺ T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K^k-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. In contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. In many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. In summary, we concluded that immunity against T. cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development.     

Specific primers for PCR amplification of the ITS1 (ribosomal DNA) of Trypanosoma lewisi

Trypanosoma lewisi is a mild or non-pathogenic parasite of the sub-genus Herpetosoma transmitted by fleas to rats. In a previous study we described pan-trypanosome specific primers TRYP1 which amplify the ITS1 of ribosomal DNA by hybridizing in highly conserved regions of 18S and 5.8S genes. These primers proved to be useful for detecting T. lewisi DNA in laboratory rats, but a recent large scale survey in wild rodents demonstrated a lack of specificity. In the present study, we designed and evaluated mono-specific primers LEW1S and LEW1R, for the detection and identification of T. lewisi by a single-step PCR. These primers were designed inside the highly variable region of the ITS1 sequence of T. lewisi ribosomal DNA. The product size of 220 bp is specific to T. lewisi. The sensitivity limit was estimated between 0.055 and 0.55 pg of DNA per reaction, equivalent to 1–10 organisms per reaction. All the PCR products obtained from 6 different T. lewisi isolates were more than 98% similar with each other and similar to the sequences of T. lewisi already published in Genbank. All DNA of 7 T. lewisi stocks from China gave the specific 220 bp product. We showed that LEW1S and LEW1R primers enabled sensitive detection and identification of T. lewisi infection in laboratory and wild rats. This assay is recommended for monitoring T. lewisi infections in rat colonies or for studying infections in the wild fauna. An absence of cross reaction with human DNA means that these primers can be used to investigate atypical trypanosome infections in humans. Given the risk of T. lewisi infection in human, we believe that these primers will be beneficial for public health diagnosis and rodents investigation programmes.     

Cyst morphology and sequence analysis of the small subunit rDNA and ef1α identifies a novel Giardia genotype in a quenda (Isoodon obesulus) from Western Australia

Sequence analysis of the small subunit ribosomal DNA (SSU-rDNA) and elongation factor 1 alpha (ef1 alpha) was performed on Giardia cysts isolated from faeces collected from a quenda (Isoodon obesulus) in the southwest of Western Australia. The SSU-rDNA and ef1 alpha were sequenced in their entirety and correspondingly aligned with the published sequence information of other known species and genotypes of Giardia. Phylogenetic analysis of the SSU-rDNA and ef1 alpha sequences identified the quenda isolate as a novel genotype of Giardia not previously reported. We believe that this quenda Giardia isolate constitutes a distinct species, which may be endemic within the Australian native fauna.     

Antigenic properties of the merozoite surface protein 1 gene of Plasmodium vivax

Plasmodium vivax is responsible for an approximate 35 million yearly human cases of malaria. Unfortunately, due to the low mortality rate associated with it and the difficulties of continuously in vitro culturing of this parasite, vaccine development against this human malaria has been largely neglected. In here, the antigenic properties of the merozoite surface protein 1 gene of P. vivax (PvMSP-1), were studied. Thus, seven recombinant bacterial plasmids coding different regions of the PvMSP-1 protein were constructed and used to immunize BALB/c mice. The results demonstrated that a plasmid encoding the entire N-terminus comprising 682 amino acids and a plasmid encoding the C-terminus including the two juxtaposed epidermal growth factor (EGF)-like domains fused to the Hepatitis B surface antigen, were antigenic. Moreover, the elicited immune responses were similar to those reported for these same PvMSP-1 regions in natural human infections.     

Synergistic enhancement of immunogenicity and protection in mice against Schistosoma japonicum with codon optimization and electroporation delivery of SjTPI DNA vaccines

Schistosomiasis is an endemic, zoonotic parasitic disease caused by Schistosoma japonicum that remains a public health concern and an effective vaccine is needed. Triose-phosphate isomerase from S. japonicum is a promising schistosome vaccine antigen shown to be immunogenic when delivered as a DNA vaccine, however, the previous S. japonicum triose-phosphate isomerase (SjTPI) DNA vaccine needs to be further optimized to achieve higher protection. In the current study, codon optimization of SjTPI DNA insert, combined with electroporation but not with the addition of a tPA leader or heat-shock protein in-frame with the SjTPI gene insert, enhanced Th1-type antibody and cytokine production and most significantly, achieved great than 50% reduction of infection against challenge with S. japonicum cercariae, a major milestone in S. japonicum vaccine development. Our results suggest that the combination of a codon optimized vaccine design and an efficient vaccine delivery system can greatly improve the potential of a SjTPI DNA vaccine as a viable schistosome vaccine candidate.     

Fluorescence analysis detects gp60 subtype diversity in Cryptosporidium infections

Ninety percent of human cryptosporidiosis infections are attributed to two species; the anthroponotic Cryptosporidium hominis and the zoonotic Cryptosporidium parvum. Sequence analysis of the hypervariable gp60 gene, which is used to classify Cryptosporidium to the subtype level, has highlighted extensive intra-species diversity within both C. hominis and C. parvum. The gp60 has also facilitated contamination source tracking and increased understanding of the epidemiology of cryptosporidiosis. Two surface glycoproteins, the gp40 and gp15 are encoded in the gp60 gene; both are exposed to the hosts’ immune system and play a pivotal role in the disease initiation process. The extent of genetic diversity observed within the gp60 would support the hypotheses of significant selection pressure placed on the gp40 and gp15. This study used a dual fluorescent terminal-restriction fragment length polymorphism (T-RFLP) analysis to investigate the genetic diversity of Cryptosporidium subtype populations in a single host infection. Terminal-RFLP showed subtype variation within one human Cryptosporidium sample and mouse samples from seven consecutive passages with C. parvum. Furthermore, this was the first study to show that differences in the ratio of subtype populations occur between infections. T-RFLP has provided a novel platform to study infection populations and to begin to investigate the impact of the hosts’ immune system on the gp60 gene.     

Field testing of Schistosoma japonicum DNA vaccines in cattle in China

Vaccines are needed to reduce the zoonotic reservoir of Schistosoma japonicum infection in bovines in China. We have developed two experimental DNA vaccines and have already shown these to be capable of inducing partial protection in water buffalo naturally exposed to the risk of S. japonicum infection in the field. We now report a similar field trial in cattle, the other major bovine reservoir host species in China. Groups of cattle were vaccinated with the VRSj28 vaccine or the VRSj23 vaccine, or, to test whether protection could be enhanced by combination vaccination, with both these DNA vaccines together. After vaccination, the cattle were exposed to natural infection in the field for a period of 54 days. Worm and egg counts carried out at the end of the experiment showed that each of the vaccine groups showed partial resistance, and that combined vaccination was not more effective than vaccination with the individual plasmids.     

Differential effects of C3d on the immunogenicity of gene gun vaccines encoding Plasmodium falciparum and Plasmodium berghei MSP142

The complement fragment C3d mediates B-cell activation via simultaneous engagement of the B-cell receptor and CD21 by antigen/C3d conjugates. Several studies demonstrated the potential of C3d as a molecular adjuvant for vaccination. In this work, C3d exerted differential effects on humoral immune responses after gene gun immunization of mice with plasmids encoding the malaria blood stage antigen MSP1₄₂ depending on the nature of the protein (Plasmodium falciparum vs. Plasmodium berghei MSP), the localization of the C3d moiety (C-terminal vs. N-terminal), and the presence of putative N-glycosylation sites. No improvement of protective efficacy by C3d attachment or mutation of glycosylation sites could be demonstrated by in vitro parasite growth inhibition assays or in vivo blood stage parasite challenges. Our data underscore the controversial role of C3d as molecular adjuvant.     

细胞色素氧化酶基因CYP1A1多态性与新疆维吾尔族人群冠心病相关性研究

目的 探讨新疆地区维吾尔(维)族人群细胞色素氧化酶基因CYP1A1多态性与冠心病的关联性。方法 使用实时PCR对293例冠心病患者(病例组)和408名健康体检者(对照组)CYP1A1基因单核苷酸多态性(SNPs:rs4886605, rs12441817, rs4646422, rs1048943)进行基因型鉴定。结果 维族人群病例组和对照组rs4886605的基因型及等位基因分布的差异均有统计学意义(均P<0.05)。病例组rs4886605显性模型(CC vs. CT+TT)基因型频率明显低于对照组。调整混杂因素后logistic回归分析表明, 维族人群rs4886605的CC基因型者患冠心病风险明显低于CT+TT基因型者(总体:OR=0.368, 95%CI:0.185～0.530, P=0.018;男性:OR=0.350, 95%CI:0.235～0.568, P=0.015)。病例组和对照组rs12441817的基因型及等位基因分布差异均有统计学意义(均P<0.05)。病例组的rs12441817显性模型(TT vs. CT+CC)基因型频率明显低于对照组。调整混杂因素后logistic回归分析表明, 维族人群rs12441817的TT基因型者患冠心病风险明显低于CT+CC基因型者(总体:OR=0.253, 95%CI:0.231～0.546, P=0.016;男性:OR=0.241, 95%CI:0.132～0.478, P=0.002)。结论 新疆维族人群CYP1A1基因多态性rs4886605、rs12441817的2个位点与发生冠心病相关。rs4886605的CC基因型、rs12441817的TT基因型可能是该人群发生冠心病的保护因素。     

Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria–pertussis–tetanus vaccines

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 μg) was intranasally (i.n.) inoculated with influenza vaccine (10 μg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3–14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 μg) was i.n. inoculated with the vaccine (10 μg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27–50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 μg) and influenza HA vaccine (1 μg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 μg) each and diphtheria–pertussis–tetanus (DPT) vaccine (10 μg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 μg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.     

一种CpG佐剂增强HIV-1DNA疫苗免疫原性的研究

目的以一种CpG寡聚核苷酸为HIV-1DNA疫苗候选佐剂,研究该CpG佐剂增强DNA疫苗免疫原性,体外促进DC细胞成熟等特点。方法在Balb/c小鼠模型上连续3次联合免疫HIV-1DNA疫苗及CpG佐剂,通过IFN-γ、IL-2ELISPOT及ELISA检测HIV特异性细胞免疫反应及体液免疫应答强度;体外制备小鼠骨髓来源的树突状细胞,通过FACS技术、高通量细胞因子检测等方法评价CpG佐剂刺激活化DC的能力。结果 CpG能够增强HIV-1DNA疫苗诱导的特异性细胞免疫反应水平,降低DNA疫苗使用剂量;CpG体外刺激原代小鼠骨髓来源的树突状细胞(BMDC),能显著上调CD40、CD80、CD86等BMDC表面共刺激分子的表达,活化BMDC并分泌各型细胞因子IL-5、IL-12p70,促炎症因子IL-1α、IL-1β、IL-6、IL-10、MIP-2、KC、MIG、Eotaxin、GM-CSF等以发挥佐剂效应。结论综合体内体外实验数据,证实该型CpG能够充分活化BMDC,显著提高HIV-1DNA疫苗免疫原性,降低疫苗使用剂量,可成为HIV-1DNA疫苗临床试验用候选佐剂。     

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the “cold chain” is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.     

鼠疫耶尔森菌csf1基因的克隆表达及其产物免疫学评价

目的表达具有免疫学活性重组F1抗原(rFl),并以其构建检测鼠疫抗体胶体金试纸条。方法将去掉信号肽编码序列的c口朋基因片段与载体质粒pET32a(+)通过BamHI和Not I双酶切位点进行连接,将重组质粒[csf1-pET32a(+)]转化入BL21(DE3)中进行诱导表达,表达产物经亲和层析纯化,以纯化rFl及天然F1抗原制备双检测鼠疫抗体胶体金标试纸条,并对浙江省528份人血清标本进行检测。结果含csf1-pET32a(+)的BL21(DE3),经诱导产生相对分子质量(M_r)约为35.5X 103的rFl融合蛋白;rFl融合蛋白检测鼠疫抗体的敏感性等同甚至超越天然F1抗原;在528份人血清标本的检测中,rFl与天然F1的符合率为97.9％(K=0.466),有较好一致性。结论制备的rFl,具有良好免疫学活性,该rFl可替代天然F1抗原,用于鼠疫免疫学检测。     

Dissection and localization of the immunostimulating domain of Edwardsiella tarda FliC

Bacterial flagellin is known to induce potent immune response in vertebrate systems via the toll-like receptor (TLR) 5. As a result, flagellin has been studied extensively as a vaccine adjuvant. In a previous study, we examined the vaccine and adjuvant potentials of the flagellin (FliC) of the fish pathogen Edwardsiella tarda. We found that E. tarda FliC induced low protective immunity by itself but could function as a molecular adjuvant and potentiate the specific immune response induced by the E. tarda antigen Eta6. Since FliC is a large protein and organized into distinct structural domains, we wondered whether the immunostimulating effect observed with the full-length protein could be localized to a certain region. To investigate this question, we in the present study dissected the FliC protein into several segments according to its structural features: (i) N163, which consists of the conserved N-terminal 163 residues of FliC; (ii) M160, which consists of the variable middle 160 residues; (iii) C94, which consists of the conserved C-terminal 94 residues; (iv) NC257, which is an artificial fusion of N163 and C94. To examine the adjuvanticity of the FliC fragments, DNA vaccine plasmids expressing FliC fragments in fusion with Eta6 were constructed and used to immunize Japanese flounder. The results showed that N163 produced the best adjuvant effect, which, in respect to improvement in the relative percent survival of the vaccinated fish, was comparable to that of the full-length FliC. None of the other FliC fragments exhibited apparent immunopotentiating effect. Further analysis showed that N163 enhanced the production of serum specific antibodies and, like full-length FliC, significantly upregulated the expression of the genes that are possibly involved in innate and adaptive immunity. These results indicate that N163 is the immunodominant region of FliC and suggest that E. tarda FliC may induce immune responses in Japanese flounder via mechanisms alternative to that involving TLR5.     

Antigen engineering can play a critical role in the protective immunity elicited by Yersinia pestis DNA vaccines

The use of a DNA immunization approach to deliver protective antigens against Yersinia pestis (Y. pestis) has been successful in previously reported studies. In the current study, the gene designs for V and F1, two well-studied virulent factors serving as main targets for vaccine development, were altered to explore additional options in hopes of improving the protective immunity of DNA vaccines expressing these two antigens. Compared to the wild type V gene DNA vaccines, the use of codon optimized V gene sequences was effective in improving the antigen expression, titers of anti-V antibody responses, and survival against a mucosal lethal challenge. For the F1 DNA vaccine, removal of the N-terminal hydrophobic region was able to improve protective immunity. However, adding a mammalian signal peptide sequence to F1 actually led to reduced protection despite it inducing slightly higher anti-F1 antibody responses. The F1 gene can be fused with a gene coding for YscF, a newly confirmed partial protective antigen for Y. pestis, to produce DNA vaccines that express fused F1 and YscF antigens. One design, in particular, that had YscF fused to the downstream sequence of F1, produced better protection than separate F1 or YscF DNA vaccines, suggesting a potential synergistic effect between these two antigens. Findings from the above studies indicated that there are multiple approaches to optimize the protective immunity for plague DNA vaccines. Most importantly, proper antigen engineering to produce optimal antigen gene inserts in DNA vaccines can clearly play a major role in the future designs of a wide range of DNA vaccines.     

Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response

Nucleic acid vaccines provide an exciting approach for antigen presentation to the immune system. As a test of this new methodology, the immune response to the in vivo-expressed Brucella abortus ribosomal L7/12 gene in the muscle cells of mice was examined. To accomplish this goal the eukaryotic expression systems pcDNA3 and p6 were used. Single intramuscular injection of the L7/L12 gene driven by the human cytomegalovirus (CMV) promoter (pcDNA3) or bovine MHC I promoter (p6) resulted in intracellular expression of the B. abortus L7/L12 immunodominant protein encoded by this gene. This application facilitated directed antigen presentation to the immune system and established specific antibody and T-cell responses compared with vector only (pcDNA₃) negative controls and B. abortus S19 injected positive controls. Although pcDNA₃-encoded L7/L12 gene-inoculated mice possessed significant protection, p6-L7/L12 did not engender significant protection against B. abortus S2308 infection compared to positive control mice. These data suggest a promising antigen-specific response, and L7/L12 nucleic acid vaccination may be an initial step in the development of genetically engineered candidate vaccines against brucellosis. This study for the first time focuses on DNA immunization of a gene from B. abortus.     

肺炎克雷伯菌、类肺炎克雷伯菌和变栖克雷伯菌的研究进展

肺炎克雷伯菌临床分离株是一种有荚膜的革兰阴性粗短杆菌,是临床上重要的机会致病菌。肺炎克雷伯菌临床分离株基因间存在差异,依据系统发育树可分为肺炎克雷伯菌(Klebsiella pneumoniae, KpⅠ)、类肺炎克雷伯菌(Klebsiella quasipneumoniae, KpⅡ)和变栖克雷伯菌(Klebsiella variicola, KpⅢ),三者生态分布、基因型、耐药性、毒力特征以及致病性存在显著差异,为感染性疾病精准治疗带来新的挑战。本文对KpⅠ、KpⅡ、KpⅢ的鉴定、流行特点及致病特点的最新研究进展进行综述。