Dominant Virulence Factor Research Articles

Microbial contamination risk of landfilled waste with different ages

Landfills are reservoirs of antibiotic resistance genes (ARGs) and pathogens, and humans are exposed to these pollutants during extensive excavation of old landfills. However, the microbial contamination risk of landfilled waste with different ages has not been assessed. In this study, human bacterial pathogens (HBPs), ARGs, and virulence factors (VFs) were systematically determined using metagenomic analysis. Results showed that the abundance of HBPs, ARGs, and VFs increased with landfill age, the percentage of HBPs in refuse with deposit age of 10–12 years (Y10) was 23.75 ± 0.49%, which was higher than that in fresh refuse (Y0, 17.99 ± 0.14%) and refuse with deposit age of 5–6 years (Y5, 19.14 ± 0.15%), indicating that old refuse had higher microbial contamination risk than fresh refuse. Multidrug, macrolide, lincosamide, streptogramine, and tetracycline resistance genes were the primary ARGs, whereas lipooligosaccharides, type IV pili, and polar flagella were the dominant VFs in refuse. The HBPs showed a significant positive correlation with ARGs and VFs. Listeria monocytogenes, Salmonella enterica, Streptococcus pneumoniae, Acinetobacter baumannii, and Escherichia coli possibly possess both multiple ARGs and VFs and could be listed as high-risk HBPs in refuse. Mobile genetic elements, especially transposons, showed positive correlations with most ARGs and VFs, and they were identified as the primary factors accounting for the variations in ARGs and VFs. These findings will help understand the spread of ARGs and VFs in landfills and evaluate the potential risk of microbiological contamination in refuse of different landfill ages, thus providing guidance for preventing disease infection during landfill excavations.

Correlation between Secreted Aspartyl Protease-5 (SAP5) on Increasing Vaginal Acidity in Vulvovaginal Candidiasis

Introduction: Vulvovaginal candidiasis (VVC) is an infection of the vaginal mucosa that extends to the vulva due to excessive growth of Candida albicans, causing a progressive decrease of Lactobacillus spp., as the main of normal flora. Decrease in the number of Lactobacillus spp. causes a reduction of lactic acid production that it was causing increasing vaginal pH. The increase in pH is due to the progressive growth of C. albicans colonies in the vaginal mucosa. In addition, the mechanism of candidiasis is also influenced by the secretion of virulence factors by C. albicans. Secreted Aspartyl Protease-5 (SAP5) is the dominant virulence factor that plays a role in changing the morphology of yeast cells into hyphae. This study aims to identify the correlation between SAP5 levels and vaginal pH. Material and Methods: This research was conducted in vivo using a sample of Rattus norvegicus with a posttest randomized experimental group design approach. This study has two groups, i.e., Negative Control (NC) and Positive Control group (PC). SAP5 and pH samples were taken from vaginal fluids and then measured using ELISA and a digital pH meter. The statistical analysis used was Pearson Correlation to analyze the correlation between SAP5 and pH levels. Results: There was a strong correlation (R=0.846) that means the increase of SAP5 is related to the increase of vaginal acidity in the PC group. Conclusion: The increase in SAP5 levels is directly followed by an increase in the pH value of vaginal fluids,

TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile

The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C.difficile, and clade 2 strains exclusively express two TcdB variants (TcdB2 and TcdB4) that use unknown receptors distinct from the classic TcdB. Here, we performed CRISPR/Cas9 screens for TcdB4 and identified tissue factor pathway inhibitor (TFPI) as its receptor. Using cryo-EM, we determined a complex structure of the full-length TcdB4 with TFPI, defining a common receptor-binding region for TcdB. Residue variations within this region divide major TcdB variants into 2 classes: one recognizes Frizzled (FZD), and the other recognizes TFPI. TFPI is highly expressed in the intestinal glands, and recombinant TFPI protects the colonic epithelium from TcdB2/4. These findings establish TFPI as a colonic crypt receptor for TcdB from clade 2 C.difficile and reveal new mechanisms for CDI pathogenesis.

Isolation and Characterization of a Novel Lytic Bacteriophage against the K2 Capsule-Expressing Hypervirulent Klebsiella pneumoniae Strain 52145, and Identification of Its Functional Depolymerase.

Klebsiella pneumoniae is among the leading bacteria that cause nosocomial infections. The capsule of this Gram-negative bacterium is a dominant virulence factor, with a prominent role in defense and biofilm formation. Bacteriophages, which are specific for one bacterial strain and its capsule type, can evoke the lysis of bacterial cells, aided by polysaccharide depolymerase enzymes. In this study, we isolated and characterized a bacteriophage against the nosocomial K. pneumoniae 52145 strain with K2 capsular serotype. The phage showed a narrow host range and stable lytic activity, even when exposed to different temperatures or detergents. Preventive effect of the phage in a nasal colonization model was investigated in vivo. Phlyogenetic analysis showed that the newly isolated Klebsiella phage B1 belongs to the Webervirus genus in Drexlerviridae family. We identified the location of the capsule depolymerase gene of the new phage, which was amplified, cloned, expressed, and purified. The efficacy of the recombinant B1dep depolymerase was tested by spotting on K. pneumoniae strains and it was confirmed that the extract lowers the thickness of the bacterium lawn as it degrades the protective capsule on bacterial cells. As K. pneumoniae strains possessing the K2 serotype have epidemiological importance, the B1 phage and its depolymerase are promising candidates for use as possible antimicrobial agents.

Label-Free Electrochemical Detection of DNA Hybridization Related to Anthrax Lethal Factor by using Carbon Nanotube Modified Sensors

Background: Anthrax Lethal Factor (ANT) is the dominant virulence factor produced by B. anthracis and is the major cause of death of infected animals. In this paper, pencil graphite electrodes GE were modified with single-walled and multi-walled carbon nanotubes (CNTs) for the detection of hybridization related to the ANT DNA for the first time in the literature. Methods: The electrochemical monitoring of label-free DNA hybridization related to ANT DNA was explored using both SCNT and MCNT modified PGEs with differential pulse voltammetry (DPV). The performance characteristics of ANT-DNA hybridization on disposable GEs were explored by measuring the guanine signal in terms of optimum analytical conditions; the concentration of SCNT and MCNT, the concentrations of probe and target, and also the hybridization time. Under the optimum conditions, the selectivity of probe modified electrodes was tested and the detection limit was calculated. Results: The selectivity of ANT probes immobilized onto MCNT-GEs was tested in the presence of hybridization of probe with NC no response was observed and with MM, smaller responses were observed in comparison to full-match DNA hybridization case. Even though there are unwanted substituents in the mixture samples containing both the target and NC in the ratio 1:1 and both the target and MM in the ratio 1:1, it has been found that ANT probe immobilized CNT modified graphite sensor can also select its target by resulting with 20.9% decreased response in comparison to the one measured in the case of full-match DNA hybridization case Therefore, it was concluded that the detection of direct DNA hybridization was performed by using MCNT-GEs with an acceptable selectivity. Conclusion: Disposable SCNT/MCNT modified GEs bring some important advantages to our assay including easy use, cost-effectiveness and giving a response in a shorter time compared to unmodified PGE, carbon paste electrode and glassy carbon electrode developed for electrochemical monitoring of DNA hybridization. Consequently, the detection of DNA hybridization related to the ANT DNA by MCNT modified sensors was performed by using lower CNT, probe and target concentrations, in a shorter hybridization time and resulting in a lower detection limit according to the SCNT modified sensors. In conclusion, MCNT modified sensors can yield the possibilities leading to the development of nucleic acid sensors platforms for the improvement of fast and cost-effective detection systems with respect to DNA chip technology.

Phylogenetic relationships, biofilm formation, motility, antibiotic resistance and extended virulence genotypes among Escherichia coli strains from women with community-onset primitive acute pyelonephritis

The present work set out to search for a virulence repertoire distinctive for Escherichia coli causing primitive acute pyelonephritis (APN). To this end, the virulence potential of 18 E. coli APN strains was genotypically and phenotypically assessed, comparatively with 19 strains causing recurrent cystitis (RC), and 16 clinically not significant (control, CO) strains. Most of the strains belong to phylogenetic group B1 (69.8%; p<0.01), and APN strains showed unique features, which are the presence of phylogroup A, and the absence of phylogroup B2 and non-typeable strains. Overall, the most dominant virulence factor genes (VFGs) were ecpA and fyuA (92.4 and 86.7%, respectively; p<0.05), and the mean number of VFGs was significantly higher in uropathogenic strains. Particularly, papAH and malX were exclusive for uropathogenic strains. APN and RC strains showed a significantly higher prevalence of fyuA, usp, and malX than of CO strains. Compared to RC strains, APN ones showed a higher prevalence of iha, but a lower prevalence of iroN, cnf1, and kpsMT-II. Hierarchical cluster analysis showed a higher proportion of two gene clusters (malX and usp, and fyuA and ecpA) were detected in the APN and RC groups than in CO, whereas iutA and iha clusters were detected more frequently in APN strains. The motility level did not differ among the study-groups and phylogroups considered, although a higher proportion of swarming strains was observed in APN strains. Antibiotic-resistance rates were generally low except for ampicillin (37.7%), and were not associated with specific study- or phylogenetic groups. APN and RC strains produced more biofilm than CO strains. In APN strains, iha was associated with higher biofilm biomass formation, whereas iroN and KpSMT-K1 were associated with a lower amount of biofilm biomass. Further work is needed to grasp the virulence and fitness mechanisms adopted by E. coli causing APN, and hence develop new therapeutic and prophylactic approaches.

Virulence Factors of Aeromonas hydrophila: In the Wake of Reclassification.

The ubiquitous “jack-of-all-trades,” Aeromonas hydrophila, is a freshwater, Gram-negative bacterial pathogen under revision in regard to its phylogenetic and functional affiliation with other aeromonads. While virulence factors are expectedly diverse across A. hydrophila strains and closely related species, our mechanistic knowledge of the vast majority of these factors is based on the molecular characterization of the strains A. hydrophila AH-3 and SSU, which were reclassified as A. piscicola AH-3 in 2009 and A. dhakensis SSU in 2013. Individually, these reclassifications raise important questions involving the applicability of previous research on A. hydrophila virulence mechanisms; however, this issue is exacerbated by a lack of genomic data on other research strains. Collectively, these changes represent a fundamental gap in the literature on A. hydrophila and confirm the necessity of biochemical, molecular, and morphological techniques in the classification of research strains that are used as a foundation for future research. This review revisits what is known about virulence in A. hydrophila and the feasibility of using comparative genomics in light of this phylogenetic revision. Conflicting data between virulence factors, secretion systems, quorum sensing, and their effect on A. hydrophila pathogenicity appears to be an artifact of inappropriate taxonomic comparisons and/or be due to the fact that these properties are strain-specific. This review audits emerging data on dominant virulence factors that are present in both A. dhakensis and A. hydrophila in order to synthesize existing data with the aim of locating where future research is needed.

Identifying copy number variation of the dominant virulence factors msa and p22 within genomes of the fish pathogen Renibacterium salmoninarum.

Renibacterium salmoninarum is the causative agent of bacterial kidney disease, an important disease of farmed and wild salmonid fish worldwide. Despite the wide spatiotemporal distribution of this disease and habitat pressures ranging from the natural environment to aquaculture and rivers to marine environments, little variation has been observed in the R. salmoninarum genome. Here we use the coverage depth from genomic sequencing corroborated by real-time quantitative PCR to detect copy number variation (CNV) among the genes of R. salmoninarum. CNV was primarily limited to the known dominant virulence factors msa and p22. Among 68 isolates representing the UK, Norway and North America, the msa gene ranged from two to five identical copies and the p22 gene ranged from one to five copies. CNV for these two genes co-occurred, suggesting they may be functionally linked. Isolates carrying CNV were phylogenetically restricted and originated predominantly from sites in North America, rather than the UK or Norway. Although both phylogenetic relationship and geographical origin were found to correlate with CNV status, geographical origin was a much stronger predictor than phylogeny, suggesting a role for local selection pressures in the repeated emergence and maintenance of this trait.

Multiple deletions in the polyketide synthase gene repertoire ofMycobacterium tuberculosisreveal functional overlap of cell envelope lipids in host-pathogen interactions

Several specific lipids of the cell envelope are implicated in the pathogenesis of M. tuberculosis (Mtb), including phthiocerol dimycocerosates (DIM) that have clearly been identified as virulence factors. Others, such as trehalose-derived lipids, sulfolipids (SL), diacyltrehaloses (DAT) and polyacyltrehaloses (PAT), are believed to be essential for Mtb virulence, but the details of their role remain unclear. We therefore investigated the respective contribution of DIM, DAT/PAT and SL to tuberculosis by studying a collection of mutants, each with impaired production of one or several lipids. We confirmed that among those with a single lipid deficiency, only strains lacking DIM were affected in their replication in lungs and spleen of mice in comparison to the WT Mtb strain. We found also that the additional loss of DAT/PAT, and to a lesser extent of SL, increased the attenuated phenotype of the DIM-less mutant. Importantly, the loss of DAT/PAT and SL in a DIM-less background also affected Mtb growth in human monocyte-derived macrophages (hMDMs). Fluorescence microscopy revealed that mutants lacking DIM or DAT/PAT were localized in an acid compartment and that bafilomycin A1, an inhibitor of phagosome acidification, rescued the growth defect of these mutants. These findings provide evidence for DIM being dominant virulence factors that mask the functions of lipids of other families, notably DAT/PAT and to a lesser extent of SL, which we showed for the first time to contribute to Mtb virulence.

RssAB-FlhDC-ShlBA as a Major Pathogenesis Pathway in Serratia marcescens

Serratia marcescens has long been recognized as an important opportunistic pathogen, but the underlying pathogenesis mechanism is not completely clear. Here, we report a key pathogenesis pathway in S. marcescens comprising the RssAB two-component system and its downstream elements, FlhDC and the dominant virulence factor hemolysin ShlBA. Expression of shlBA is under the positive control of FlhDC, which is repressed by RssAB signaling. At 37°C, functional RssAB inhibits swarming, represses hemolysin production, and promotes S. marcescens biofilm formation. In comparison, when rssBA is deleted, S. marcescens displays aberrant multicellularity favoring motile swarming with unbridled hemolysin production. Cellular and animal infection models further demonstrate that loss of rssBA transforms this opportunistic pathogen into hypervirulent phenotypes, leading to extensive inflammatory responses coupled with destructive and systemic infection. Hemolysin production is essential in this context. Collectively, a major virulence regulatory pathway is identified in S. marcescens.

Enterotoxigenic Escherichia coli (K88) induce proinflammatory responses in porcine intestinal epithelial cells

Infections with F4 + enterotoxigenic Escherichia coli (ETEC) causes severe diarrhoea in piglets, resulting in morbidity and mortality. F4 fimbriae are the key virulence factors mediating the attachment of F4 + ETEC to the intestinal epithelium. Intestinal epithelial cells (IEC) are recently being recognized as important regulators of the intestinal immune system through the secretion of cytokines, however, data on how F4 + ETEC affect this cytokine secretion are scarce. By using ETEC strains expressing either polymeric, monomeric or F4 fimbriae with a reduced polymeric stability, we demonstrated that polymeric fimbriae are essential for adhesion to porcine IEC and the secretion of IL-6 and IL-8 by IEC. Remarkably, this cytokine secretion was not abrogated following stimulation with an F4-negative strain. Since this strain expresses flagellin, TLR5 mediated signalling could be involved. Indeed, porcine IEC express TLR5 and purified flagellin induced IL-6 and IL-8 secretion, indicating that, as for other pathogens, flagellin is the dominant virulence factor involved in the induction of proinflammatory responses in IEC. These results indicate a potential mucosal adjuvant capacity of ETEC-derived flagellin and may improve rational vaccine design against F4 + ETEC infections.

Discriminating Virulence Mechanisms amongBacillus anthracisStrains by Using a Murine Subcutaneous Infection Model

Bacillus anthracis strains harboring virulence plasmid pXO1 that encodes the toxin protein protective antigen (PA), lethal factor, and edema factor and virulence plasmid pXO2 that encodes capsule biosynthetic enzymes exhibit different levels of virulence in certain animal models. In the murine model of pulmonary infection, B. anthracis virulence was capsule dependent but toxin independent. We examined the role of toxins in subcutaneous (s.c.) infections using two different genetically complete (pXO1(+) pXO2(+)) strains of B. anthracis, strains Ames and UT500. Similar to findings for the pulmonary model, toxin was not required for infection by the Ames strain, because the 50% lethal dose (LD(50)) of a PA-deficient (PA(-)) Ames mutant was identical to that of the parent Ames strain. However, PA was required for efficient s.c. infection by the UT500 strain, because the s.c. LD(50) of a UT500 PA(-) mutant was 10,000-fold higher than the LD(50) of the parent UT500 strain. This difference between the Ames strain and the UT500 strain could not be attributed to differences in spore coat properties or the rate of germination, because s.c. inoculation with the capsulated bacillus forms also required toxin synthesis by the UT500 strain to cause lethal infection. The toxin-dependent phenotype of the UT500 strain was host phagocyte dependent, because eliminating Gr-1(+) phagocytes restored virulence to the UT500 PA(-) mutant. These experiments demonstrate that the dominant virulence factors used to establish infection by B. anthracis depend on the route of inoculation and the bacterial strain.

Staphylococcus Epidermidis Induced Platelet Aggregation Is Mediated by the Fibrinogen Binding Surface Protein SdrG.

S. epidermidis is normally present on the surface of the skin, however in a hospital setting, it is responsible for many infections involving implanted medical devices resulting in potentially fatal complications such as infective endocarditis and septicemia. S. epidermidis has previously been shown to induce platelet aggregation (Ohshima et al. Microbiol Immunol 1991) through an unknown mechanism. The surface protein SdrG (serine-aspartate repeat G protein) is important in the initial colonization of the device, as it binds fibrinogen, which is one of the first proteins to coat foreign devices. We thus postulated that this SdrG fibrinogen complex may mediate the S. epidermidis interaction with platelets. In order to investigate the specific effects of SdrG on platelets, we expressed SdrG in Lactococcus lactis which does not activate platelets. L. lactis SdrG was able to support platelet adhesion in the absence of fibrinogen, and to a greater extent in the presence of fibrinogen suggesting both a direct interaction with the platelet and an indirect interaction via a fibrinogen bridge. Fibrinogen dependent adhesion was inhibited by both abciximab and tirofiban confirming an interaction with GPIIb/IIIa. Furthermore, SdrG when expressed in L. lactis can induce platelet aggregation with a lag time of 1.5 ± 0.4 min. This aggregation was inhibited by abciximab suggesting that it is true aggregation rather than agglutination. We have also shown this to be dependent on cyclooxygenase signalling, as it is inhibited by aspirin. SdrG binds to the C-terminus of the beta chain of fibrinogen (Ponnuraj K et al. , Cell 2003). We synthesized a 15-mer peptide mimicking the binding region of the fibrinogen beta chain in order to determine whether fibrinogen binding was important for this aggregation. The native fibrinopeptide NEEGFFSARGHRPLD increased the lag time for aggregation to 9.2 ± 1.4 min, however, the control peptide NEEGFFAARGHRPLD did not affect aggregation (1.4 ± 0.3 min). The lag time did not increase further with saturating concentrations of peptide concentrations suggesting instability of the peptide, or a second mechanism involved in the aggregation which is consistent with the fibrinogen independent interaction seen in the adhesion assay. This work shows that SdrG alone is sufficient to support platelet adhesion and aggregation. SdrG mediates platelet activation through a novel mechanism via GPIIb/IIIa, and an as yet unknown direct interaction. Thus SdrG appears to be the dominant virulence factor for S. epidermidis induced thrombosis, therefore, inhibition of these interactions have potential for treatment of thrombotic complications associated with S. epidermidis infections.

Neutralizing monoclonal antibody against Anthrax lethal factor inhibits intoxication in a mouse model

Anthrax toxin is the dominant virulence factor of Bacillus anthracis; drugs blocking its action could therefore have therapeutic benefit. We report here the production of a neutralizing monoclonal antibody (mAb) against anthrax lethal factor (LF) and the inhibition by the antibody of anthrax lethal toxin (LeTx) formation. The anti-LF monoclonal antibody LF8 neutralized the LeTx challenge both in vitro with macrophage J774A.1 cells and in vivo in nude mice. Our data suggested that LF8 binds LF at or near the PA binding domain. A set of dodecameric peptides was selected from a phage-displayed peptide library through their specific binding to anti-LF neutralizing mAb LF8. These small peptides compete with LF to bind LF8. Further investigation is undergoing to test the potential application of these peptides to the clinical treatment of anthrax infection by blocking LeTx formation.

Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides.

The anthrax lethal factor (LF), a Zn-dependent endopeptidase, is considered the dominant virulence factor of anthrax. Because pharmacological inhibition of the catalytic activity of LF is considered a plausible mechanism for preventing the lethality of anthrax, a high-throughput screening experiment based on LF-catalyzed cleavage of a fluorescent substrate was performed to identify novel inhibitors of LF. The RNA-targeting antibiotics, neomycin B and some synthetic dimeric aminoglycosides, were found to be nanomolar active-site inhibitors of LF.

Pore worms: Using Caenorhabditis elegans to study how bacterial toxins interact with their target host

AbstractThe interaction of pathogenic bacteria with a target host is regulated both by bacterial virulence factors and by host components that either protect the host or that promote pathogenesis. The soil nematode Caenorhabditis elegans is a host for a number of bacterial pathogens, as briefly reviewed here. Bacillus thuringiensis (Bt) is a pathogenic bacteria that C. elegans is likely to encounter naturally in the soil. The pore-forming Crystal (Cry) toxins made by Bt are recognized as the dominant virulence factor in this host-pathogen interaction. Forward genetic screens for C. elegans mutants resistant to the Cry toxin, Cry5B, have identified a host carbohydrate structure that promotes pathogenesis. Data suggest this structure is likely to be a Cry5B receptor expressed in the host intestine. This finding is discussed in light of other carbohydrate receptors for bacterial toxins. To investigate host-toxin interactions on a global level, the response of C. elegans to the pore-forming Cry5B is also being investigated by gene transcription profiling (microarrays). These data are beginning to reveal a diverse intracellular response to toxin exposure. To put these investigations in perspective, host responses to other pore-forming toxins are discussed. Investigations with Cry5B in C. elegans show a promising beginning in helping to elucidate host-toxin and host-pathogen interactions.

Association Between Virulence Factors and Clinical Course of Escherichia coli Mastitis

Mastitis caused by Escherichia coli is common in lactating dairy cows. E. coli is considered to be an opportunistic pathogen and originate from a contaminated environment [7]. The severity and course of the disease vary greatly and mainly depend on cow's response [4]. However, the virulence of the bacterial strain involved may also play a role. Bacteria require virulence factors to colonize, multiply and survive in the udder. These include toxins, adhesins, invasins, capsule production and the ability to resist serum complement and scavenge iron. Dominant virulence factors have not been identified in mastitis-derived E. coli isolates [5]. In this study we investigated the association between virulence factors of the isolated bacteria and the clinical course in bovine E. coli mastitis.

Gene regulation and host adaptation mechanisms in Candida albicans

Abstract The yeast Candida albicans is a harmless member of the normal microflora on the mucosal surfaces of most healthy persons, but it can cause severe opportunistic infections in immunosuppressed patients. To become a successful human commensal and pathogen, C. albicans has evolved host adaptation mechanisms on different levels. The regulated expression of virulence and other genes in response to environmental signals allows an optimal adaptation to new host niches during the course of an infection. In addition, C. albicans is able to switch between different cell types in a reversible and apparently random fashion. Phenotypic switching involves the coordinated regulation of phase-specific genes, and the resulting generation of selected, pre-programmed cell types may represent an additional strategy to adapt to certain host environments. Finally, C. albicans produces genetically altered variants at a high rate. This microevolution ensures survival when the pathogen encounters new adverse conditions, as exemplified by the development of stable drug-resistant variants under the selection pressure caused by antimycotic therapy. Thus, rather than the possession of single dominant virulence factors, it is its remarkable versatility that makes C. albicans the most important fungal pathogen of humans.

Anthrax toxins.

Though its lethal effects were ascribed to an exotoxin almost half a century ago, the pathogenesis of anthrax has yet to be satisfactorily explained. Subsequent work has led to the molecular identification and enzymatic characterization of three proteins that constitute two anthrax toxins. Protective antigen binds an as yet unknown cell receptor and mediates the entry of the other two components to the cytoplasm via the endosomal pathway. Edema factor, so named for its ability to induce edema, is a Ca2+/calmodulin-dependent adenylate cyclase. Lethal factor, the dominant virulence factor associated with the toxin, proteolytically inactivates mitogen-activated protein kinase kinases, key players in signal transduction. We describe the fascinating work that has led to these discoveries and discuss their relevance to our understanding of the pathogenesis of anthrax.

Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenic spread of experimental Klebsiella pneumoniae pneumonia.

Klebsiella pneumoniae is an important nosocomial pathogen causing severe pulmonary infections. The majority of clinical Klebsiella isolates produce a high-molecular-weight capsular polysaccharide (CPS) which is one of the dominant virulence factors. In the present study, we examined the potency of a murine immunoglobulin M monoclonal antibody (MAb) with specificity to Klebsiella type 2 CPS to protect rats against experimental Klebsiella pneumonia. The MAb did not prevent the invasion of virulent bacteria into the interalveolar space. However, the resolution of infection was accelerated in MAb-treated animals. This was demonstrated by (i) less severe weight loss and (ii) markedly reduced inflammatory reactions in the lung. The elimination of bacteria was significantly increased not only in the lungs but also in the livers of antibody-treated rats. This was reflected by reduced levels of circulating, soluble CPS and MAb-bound CPS. A mixture of human MAbs with specificity to CPS of clinically important Klebsiella serotypes may prove to be a useful tool for the prevention or supportive treatment of Klebsiella pneumonia.