scholarly journals Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

2012 ◽  
Vol 19 (5) ◽  
pp. 675-683 ◽  
Author(s):  
Apichaya Puangpetch ◽  
Robert Anderson ◽  
Yan Y. Huang ◽  
Rasana W. Sermswan ◽  
Wanpen Chaicumpa ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Severe Disease ◽  
Antimicrobial Activities ◽  
Cationic Liposomes ◽  
Phagocytic Index ◽  
Cpg Odn ◽  
Content Type ◽  
Cpg Oligodeoxynucleotide ◽  
Alternative Approach ◽  
Lethal Infection

ABSTRACTMelioidosis is a severe disease caused by the Gram-negative bacteriumBurkholderia pseudomallei. Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior toB. pseudomalleichallenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN againstB. pseudomalleiinfection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection againstB. pseudomalleiinfection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available.

scholarly journals CpG Oligodeoxynucleotide 2006 and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

2011 ◽  
Vol 55 (7) ◽  
pp. 3461-3464 ◽  
Author(s):  
Suman Gupta ◽  
Shraddha A. Sane ◽  
Nishi Shakya ◽  
Preeti Vishwakarma ◽  
W. Haq
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Inhibitory Effect ◽  
Rational Approach ◽  
Host Use ◽  
Cpg Odn ◽  
Content Type ◽  
Cpg Oligodeoxynucleotide ◽  
Class B ◽  
Different Doses

ABSTRACTIn view of the severe immunosuppression in visceral leishmaniasis (VL), a rational approach to effectively combat the parasitic scourge would be to enhance the immune status of the host. Use of CpG oligodeoxynucleotide (CpG-ODN) against leishmaniasis has previously been reported, especially as an immunomodulator and adjuvant with various immunogens. In the present study, experiments were carried out with BALB/c mice and hamsters infected withLeishmania donovani. Immunostimulating class B bacterial CpG-ODN namely, ODN-2006, was administered at various doses by the intraperitoneal (i.p.) route. The dose of CpG-ODN-2006 (1 nM/single dose) showing the most antileishmanial activity was given as free and liposomal forms with different doses of miltefosine, namely, 5 and 10 mg/kg of body weight, for 5 days in mice and hamsters, respectively. Among the various groups, mice coadministered liposomal CpG-ODN and miltefosine (5 mg/kg) showed the best inhibitory effect (97% parasite inhibition) compared with free CpG-ODN plus miltefosine and miltefosine, free CpG-ODN, and liposomal CpG-ODN given separately. Similar responses were observed in the case of hamsters, where the combination of liposomal CpG-ODN with miltefosine (10 mg/kg) gave 96% parasite inhibition. Promising antileishmanial efficacy was observed in animals treated with liposomal CpG-ODN and miltefosine.

scholarly journals Colony Morphology Variation of Burkholderia pseudomallei Is Associated with Antigenic Variation and O-Polysaccharide Modification

2015 ◽  
Vol 83 (5) ◽  
pp. 2127-2138 ◽  
Author(s):  
Chanthiwa Wikraiphat ◽  
Natnaree Saiprom ◽  
Sarunporn Tandhavanant ◽  
Christian Heiss ◽  
Parastoo Azadi ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Antigenic Variation ◽  
Structural Characteristics ◽  
Severe Disease ◽  
Conformational Epitope ◽  
Methyl Transferase ◽  
Content Type ◽  
Persistent Infections ◽  
Tier 1 ◽  
Potential Vaccine

Burkholderia pseudomalleiis a CDC tier 1 select agent that causes melioidosis, a severe disease in humans and animals. Persistent infections are common, and there is currently no vaccine available. Lipopolysaccharide (LPS) is a potential vaccine candidate.B. pseudomalleiexpresses three serologically distinct LPS types. The predominant O-polysaccharide (OPS) is an unbranched heteropolymer with repeatingd-glucose and 6-deoxy-l-talose residues in which the 6-deoxy-l-talose residues are variably replaced withO-acetyl andO-methyl modifications. We observed that primary clinicalB. pseudomalleiisolates with mucoid and nonmucoid colony morphologies from the same sample expressed different antigenic types distinguishable using an LPS-specific monoclonal antibody (MAb). MAb-reactive (nonmucoid) and nonreactive (mucoid) strains from the same patient exhibited identical LPS banding patterns by silver staining and indistinguishable genotypes. We hypothesized that LPS antigenic variation reflected modification of the OPS moieties. Mutagenesis of three genes involved in LPS synthesis was performed inB. pseudomalleiK96243. Loss of MAb reactivity was observed in bothwbiA(encoding a 2-O-acetyltransferase) andwbiD(putative methyl transferase) mutants. The structural characteristics of the OPS moieties from isogenic nonmucoid strain 4095a and mucoid strain 4095c were further investigated. Utilizing nuclear magnetic resonance (NMR) spectroscopy, we found thatB. pseudomallei4095a and 4095c OPS antigens exhibited substitution patterns that differed from the prototypic OPS structure. Specifically, 4095a lacked 4-O-acetylation, while 4095c lacked both 4-O-acetylation and 2-O-methylation. Our studies indicate thatB. pseudomalleiOPS undergoes antigenic variation and suggest that the 9D5 MAb recognizes a conformational epitope that is influenced by bothO-acetyl andO-methyl substitution patterns.

scholarly journals Burkholderia pseudomallei Capsular Polysaccharide Conjugates Provide Protection against Acute Melioidosis

2014 ◽  
Vol 82 (8) ◽  
pp. 3206-3213 ◽  
Author(s):  
Andrew E. Scott ◽  
Mary N. Burtnick ◽  
Margaret G. M. Stokes ◽  
Adam O. Whelan ◽  
E. Diane Williamson ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Capsular Polysaccharide ◽  
High Titer ◽  
Severe Disease ◽  
Lethal Dose ◽  
Survival Rates ◽  
Etiologic Agent ◽  
Content Type ◽  
Covalently Linked ◽  
Study Type

ABSTRACTBurkholderia pseudomallei, the etiologic agent of melioidosis, is a CDC tier 1 select agent that causes severe disease in both humans and animals. Diagnosis and treatment of melioidosis can be challenging, and in the absence of optimal chemotherapeutic intervention, acute disease is frequently fatal. Melioidosis is an emerging infectious disease for which there are currently no licensed vaccines. Due to the potential malicious use ofB. pseudomalleias well as its impact on public health in regions where the disease is endemic, there is significant interest in developing vaccines for immunization against this disease. In the present study, type A O-polysaccharide (OPS) andmanno-heptose capsular polysaccharide (CPS) antigens were isolated from nonpathogenic, select-agent-excluded strains ofB. pseudomalleiand covalently linked to carrier proteins. By using these conjugates (OPS2B1 and CPS2B1, respectively), it was shown that although high-titer IgG responses against the OPS or CPS component of the glycoconjugates could be raised in BALB/c mice, only those animals immunized with CPS2B1 were protected against intraperitoneal challenge withB. pseudomallei. Extending upon these studies, it was also demonstrated that when the mice were immunized with a combination of CPS2B1 and recombinantB. pseudomalleiLolC, rather than with CPS2B1 or LolC individually, they exhibited higher survival rates when challenged with a lethal dose ofB. pseudomallei. Collectively, these results suggest that CPS-based glycoconjugates are promising candidates for the development of subunit vaccines for immunization against melioidosis.

scholarly journals Immunostimulatory CpG Oligodeoxynucleotide Confers Protection in a Murine Model of Infection with Burkholderia pseudomallei

2004 ◽  
Vol 72 (8) ◽  
pp. 4494-4502 ◽  
Author(s):  
Surasakdi Wongratanacheewin ◽  
Wannapa Kespichayawattana ◽  
Pakamas Intachote ◽  
Sathit Pichyangkul ◽  
Rasana W. Sermswan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Burkholderia Pseudomallei ◽  
Bacterial Load ◽  
Elevated Serum ◽  
Interleukin 12 ◽  
Cpg Odn ◽  
Bacterial Challenge ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Oligodeoxynucleotide ◽  
Ifn Γ

ABSTRACT Although CpG oligodeoxynucleotides (CpG ODNs) are known to enhance resistance against infection in a number of animal models, little is known about the CpG-induced protection against acute fatal sepsis such as that associated with the highly virulent bacterium Burkholderia pseudomallei. We previously demonstrated in an in vitro study that immunostimulatory CpG ODN 1826 enhances phagocytosis of B. pseudomallei and induces nitric oxide synthase and nitric oxide production by mouse macrophages. In the present study, CpG ODN 1826 given intramuscularly to BALB/c mice 2 to 10 days prior to B. pseudomallei challenge conferred better than 90% protection. CpG ODN 1826 given 2 days before the bacterial challenge rapidly enhanced the innate immunity of these animals, judging from the elevated serum levels of interleukin-12 (IL-12)p70 and gamma interferon (IFN-γ) over the baseline values. No bacteremia was detected on day 2 in 85 to 90% of the CpG-treated animals, whereas more than 80% of the untreated animals exhibited heavy bacterial loads. Although marked elevation of IFN-γ was found consistently in the infected animals 2 days after the bacterial challenge, it was ameliorated by the CpG ODN 1826 pretreatment (P = 0.0002). Taken together, the kinetics of bacteremia and cytokine profiles presented are compatible with the possibility that protection by CpG ODN 1826 against acute fatal septicemic melioidosis in this animal model is associated with a reduction of bacterial load and interference with the potential detrimental effect of the robust production of proinflammatory cytokines associated with B. pseudomallei multiplication.

scholarly journals Intranasal Prophylaxis with CpG Oligodeoxynucleotide Can Protect against Yersinia pestis Infection

2013 ◽  
Vol 81 (6) ◽  
pp. 2123-2132 ◽  
Author(s):  
Anthony J. Hickey ◽  
Jr-Shiuan Lin ◽  
Lawrence W. Kummer ◽  
Frank M. Szaba ◽  
Debra K. Duso ◽  
...  
Keyword(s):  
T Cells ◽  
Yersinia Pestis ◽  
Bacterial Growth ◽  
Virulent Strain ◽  
Hepatic Tissue ◽  
Cpg Odn ◽  
Prophylactic Regimen ◽  
Term Survival ◽  
Content Type ◽  
Cpg Oligodeoxynucleotide

ABSTRACTImmunomodulatory agents potentially represent a new class of broad-spectrum antimicrobials. Here, we demonstrate that prophylaxis with immunomodulatory cytosine-phosphate-guanidine (CpG) oligodeoxynucleotide (ODN), a toll-like receptor 9 (TLR9) agonist, confers protection againstYersinia pestis, the etiologic agent of plague. The data establish that intranasal administration of CpG ODN 1 day prior to lethal pulmonary exposure toY. pestisstrain KIM D27 significantly improves survival of C57BL/6 mice and reduces bacterial growth in hepatic tissue, despite paradoxically increasing bacterial growth in the lung. All of these CpG ODN-mediated impacts, including the increased pulmonary burden, are TLR9 dependent, as they are not observed in TLR9-deficient mice. The capacity of prophylactic intranasal CpG ODN to enhance survival does not require adaptive immunity, as it is evident in mice lacking B and/or T cells; however, the presence of T cells improves long-term survival. The prophylactic regimen also improves survival and reduces hepatic bacterial burden in mice challenged intraperitoneally with KIM D27, indicating that intranasal delivery of CpG ODN has systemic impacts. Indeed, intranasal prophylaxis with CpG ODN provides significant protection against subcutaneous challenge withY. pestisstrain CO92 even though it fails to protect mice from intranasal challenge with that fully virulent strain.

scholarly journals Wsp1, a GBD/CRIB Domain-Containing WASP Homolog, Is Required for Growth, Morphogenesis, and Virulence of Cryptococcus neoformans

2011 ◽  
Vol 10 (4) ◽  
pp. 521-529 ◽  
Author(s):  
Gui Shen ◽  
Amy Whittington ◽  
Ping Wang
Keyword(s):  
Cryptococcus Neoformans ◽  
Actin Polymerization ◽  
Divergent Evolution ◽  
Phagocytic Index ◽  
Fungal Virulence ◽  
Actin Reorganization ◽  
Content Type ◽  
Lethal Infection ◽  
Endocytic Protein

ABSTRACTHuman endocytic protein ITSN1 regulates actin reorganization by activating Rho family GTPases, such as Cdc42. The process is enhanced by ITSN binding of WASP, an effector of Cdc42 and a potent activator of actin polymerization. In the human pathogenCryptococcus neoformans, endocytic protein Cin1 also interacts with Cdc42 and Wsp1, an uncharacterized WASP homolog, but the significance of these interactions remains unknown. Wsp1 contains several conserved domains, including a WASP homology 1 domain (WH1), a GTPase binding/Cdc42 and Rac interactive binding domain (GBD/CRIB), and a C-terminal domain composed of verprolin-like, central, and acidic motifs (VCA). Thus, Wsp1 exhibits domain compositions more similar to human WASP proteins thanSaccharomyces cerevisiaeLas17/Bee1, a WASP homolog lacking the GDB/CRIB domain. Wsp1 is not an essential protein; however, thewsp1mutant exhibited defects in growth, cytokinesis, chitin distribution, and endocytosis and exocytosis. Thewsp1mutant was also unable to undergo genetic cross, produce the polysaccharide capsule, or secrete the enzyme urease. Anin vitrophagocytosis assay showed a higher phagocytic index for thewsp1mutant, whose ability to cause lethal infection in a murine model of cryptococcosis was also attenuated. Our studies reveal divergent evolution of WASP proteins in the fungal phylum and suggest that the conserved function of WASP proteins in the actin cytoskeleton may also impact fungal virulence.

scholarly journals Synergistic Effect of Combined Application of a New Fungicide Fluopimomide with a Biocontrol Agent Bacillus methylotrophicus TA-1 for Management of Gray Mold in Tomato

Plant Disease ◽  
2019 ◽  
Vol 103 (8) ◽  
pp. 1991-1997 ◽  
Author(s):  
Xiaoxue Ji ◽  
Jingjing Li ◽  
Zhen Meng ◽  
Shouan Zhang ◽  
Bei Dong ◽  
...  
Keyword(s):  
Field Experiments ◽  
Biocontrol Agent ◽  
Severe Disease ◽  
Combined Treatment ◽  
Field Trials ◽  
Antimicrobial Activities ◽  
Gray Mold ◽  
Control Efficacy ◽  
Bacillus Methylotrophicus

Gray mold caused by Botrytis cinerea can be a severe disease of tomato infecting leaves and fruits of tomato plants. Chemical control is currently the most effective and reliable method; however, application of fungicides has many drawbacks. The combination of biological control agents with newly developed fungicides may be a practicable method to control B. cinerea. Fluopimomide is a newly developed fungicide with a novel mode of action. Bacillus methylotrophicus TA-1, isolated from rhizosphere soil of tomato, is a bacterial strain with a broad spectrum of antimicrobial activities. Little information is currently available about the effect of fluopimomide and its integrated effect on B. cinerea. Therefore, laboratory, pot, and field experiments were carried out to determine the effects of fluopimomide alone and in combination with B. methylotrophicus TA-1 against gray mold on tomato. The in vitro growth of B. methylotrophicus TA-1 was unaffected by 100 mg liter−1 fluopimomide. Inhibition of B. cinerea mycelial growth was significantly increased under combined treatment of fluopimomide and B. methylotrophicus TA-1. In greenhouse experiments, efficacy against gray mold was significantly greater by an integration of fluopimomide and B. methylotrophicus TA-1 than by either alone; control efficacy of fluopimomide at 50 and 100 g ha−1 in combination with B. methylotrophicus TA-1 at 108 colony-forming units (cfu) ml−1 reached 70.16 and 69.32%, respectively, compared with the untreated control. In both field trials during 2017 and 2018, control efficacy was significantly higher for the combination of fluopimomide at 50 and 100 g ha−1 in combination with B. methylotrophicus TA-1 than for either treatment alone. The results from this study indicated that integration of the new fungicide fluopimomide with the biocontrol agent B. methylotrophicus TA-1 synergistically increased control efficacy of the fungicide against gray mold of tomato.

Numerical analysis of the shear strength of circular reinforced concrete columns subjected to cyclic lateral loads using linear genetic programming

2020 ◽  
Vol 37 (7) ◽  
pp. 2517-2537
Author(s):  
Mostafa Rezvani Sharif ◽  
Seyed Mohammad Reza Sadri Tabaei Zavareh
Keyword(s):  
Numerical Modeling ◽  
Shear Strength ◽  
Reinforced Concrete ◽  
Numerical Analysis ◽  
Genetic Programming ◽  
Linear Genetic Programming ◽  
Rc Columns ◽  
Content Type ◽  
Alternative Approach ◽  
Engineering Problems

Purpose The shear strength of reinforced concrete (RC) columns under cyclic lateral loading is a crucial concern, particularly, in the seismic design of RC structures. Considering the costly procedure of testing methods for measuring the real value of the shear strength factor and the existence of several parameters impacting the system behavior, numerical modeling techniques have been very much appreciated by engineers and researchers. This study aims to propose a new model for estimation of the shear strength of cyclically loaded circular RC columns through a robust computational intelligence approach, namely, linear genetic programming (LGP). Design/methodology/approach LGP is a data-driven self-adaptive algorithm recently used for classification, pattern recognition and numerical modeling of engineering problems. A reliable database consisting of 64 experimental data is collected for the development of shear strength LGP models here. The obtained models are evaluated from both engineering and accuracy perspectives by means of several indicators and supplementary studies and the optimal model is presented for further purposes. Additionally, the capability of LGP is examined to be used as an alternative approach for the numerical analysis of engineering problems. Findings A new predictive model is proposed for the estimation of the shear strength of cyclically loaded circular RC columns using the LGP approach. To demonstrate the capability of the proposed model, the analysis results are compared to those obtained by some well-known models recommended in the existing literature. The results confirm the potential of the LGP approach for numerical analysis of engineering problems in addition to the fact that the obtained LGP model outperforms existing models in estimation and predictability. Originality/value This paper mainly represents the capability of the LGP approach as a robust alternative approach among existing analytical and numerical methods for modeling and analysis of relevant engineering approximation and estimation problems. The authors are confident that the shear strength model proposed can be used for design and pre-design aims. The authors also declare that they have no conflict of interest.

scholarly journals Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors

2012 ◽  
Vol 80 (11) ◽  
pp. 3921-3929 ◽  
Author(s):  
Donporn Riyapa ◽  
Surachat Buddhisa ◽  
Sunee Korbsrisate ◽  
Jon Cuccui ◽  
Brendan W. Wren ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Capsular Polysaccharide ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Predisposing Factor ◽  
Bacterial Killing ◽  
Content Type ◽  
Extracellular Traps ◽  
Type Iii Protein Secretion

ABSTRACTBurkholderia pseudomalleiis the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing ofB. pseudomalleiremains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response toB. pseudomalleiin a dose- and time-dependent manner.B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways.B. pseudomalleimutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.

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