Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene coding for the acetyl-CoA synthetase (ADP-forming) from the amitochondriate eukaryote Giardia lamblia has been expressed in Escherichia coli. The recombinant enzyme exhibited the same substrate specificity as the native enzyme, utilizing acetyl-CoA and adenine nucleotides as preferred substrates and less efficiently, propionyl- and succinyl-CoA. N- and C-terminal parts of the G. lamblia acetyl-CoA synthetase sequence were found to be homologous to the alpha- and beta-subunits, respectively, of succinyl-CoA synthetase. Sequence analysis of homologous enzymes from various bacteria, archaea, and the eukaryote, Plasmodium falciparum, identified conserved features in their organization, which allowed us to delineate a new superfamily of acyl-CoA synthetases (nucleoside diphosphate-forming) and its signature motifs. The representatives of this new superfamily of thiokinases vary in their domain arrangement, some consisting of separate alpha- and beta-subunits and others comprising fusion proteins in alpha-beta or beta-alpha orientation. The presence of homologs of acetyl-CoA synthetase (ADP-forming) in such human pathogens as G. lamblia, Yersinia pestis, Bordetella pertussis, Pseudomonas aeruginosa, Vibrio cholerae, Salmonella typhi, Porphyromonas gingivalis, and the malaria agent P. falciparum suggests that they might be used as potential drug targets.
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PMID:Acetyl-CoA synthetase from the amitochondriate eukaryote Giardia lamblia belongs to the newly recognized superfamily of acyl-CoA synthetases (Nucleoside diphosphate-forming). 1068 68

A protocol was developed for significantly reducing resident midgut bacteria in newly emerged anopheline mosquitoes using a combination of antibiotics. Pupa harvested from colony-reared Anopheles gambiae s.l. Giles and Anopheles stephensi (Liston) were placed in cages wiped previously with 70% alcohol and kept under UV light for 24 h. Emerging adult mosquitoes were fed for 3 consecutive days on antibiotic solution, consisting of 0.4% gentamicin sulfate and 1% penicillin-streptomycin solution in a 10% sterile sucrose solution. Bacterial suspensions of Escherichia coli, Klebsiella pneumoniae (Schroeter, 1886), and Pseudomonas stutzeri (Lehmann & Neumann, 1896) isolated from wild-caught anophelines were fed to antibiotic-treated mosquitoes starved for 24 h via either sugar or membrane-feeding. Mosquitoes dissected 1 and 24 h after blood-feeding or sugar-feeding, and plated on trypticase soy agar plates, yielded the same type of bacteria fed originally without evidence of contaminants. There was no residual effect of the antibiotics on introduced single bacteria strains as judged by the presence of bacteria in antibiotic-treated mosquitoes. This experimental reduction of resident midgut bacteria and their replacement with single strains in newly emerged anopheline mosquitoes should facilitate further investigations of the interactions between malaria parasites and bacteria found in the midguts of mosquitoes.
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PMID:Bactericidal effects of sugar-fed antibiotics on resident midgut bacteria of newly emerged anopheline mosquitoes (Diptera: Culicidae). 1073 Apr 95

The global challenge of optimally treating bacterial infections is continuously evolving. Azithromycin, the first azalide antibiotic, presents pharmacokinetics and pharmacodynamics that allow for a simple dosing regimen with minimal side effects. Current azithromycin uses include a variety of community-acquired respiratory tract, skin and soft tissue, and sexually transmitted disease infections. Azithromycin has also demonstrated substantial activity against atypical organisms such as Mycobacterium avium complex (MAC) and Chlamydia trachomatis. Due to a never-ending need for new antibiotic therapies, several other potential indications for azithromycin are being researched. This article will present various current research associated with azithromycin's potential use for malaria, trachoma, coronary artery disease (CAD), Pseudomonas aeruginosa infections, erythema migrans, short-term therapy for respiratory infections, typhoid, cryptosporidiosis, pelvic inflammatory disease, acne, Mediterranean spotted fever and MAC. As bacterial and parasite resistance patterns fluctuate globally, azithromycin may be an alternative therapy for the previously mentioned indications, which will also enhance patient compliance and therefore effectively eradicate infection worldwide.
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PMID:Azithromycin: indications for the future? 1124 33

beta Androstenes steroid up-regulates immunity to increase resistance against lethal infection and lethal radiation, and mediates a rapid recovery of hematopoietic precursor cells after radiation injury. beta Androstenetriol increases the levels of the TH(1) cytokines, IL-2, IL-3, IFN gamma and counteracts hydrocortisone mediated immune suppression. In contrast, 17 alpha androstenediol inhibits proliferation and mediates apoptosis in tumor cells of murine and human origin. Its epimer 17beta androstenediol does not. The antiproliferative functions of 17 alpha androstenediol are not dependent on either the estrogen or androgen receptors. Our findings show that beta androstenes and analogs protect the host from lethal infection by DNA or RNA viruses such as, herpesvirus type 2, coxsackievirus B4, influenza, and arthropod borne viruses. These androstenes also protected the host from lethal bacterial infections by Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumonia and from parasites infections, i.e. Cryptosporidium parvum, and malaria. In vivo, the level of potency follows the order: dehydroepiandrosterone<<<androstenediol<androstenetriol with the latter being up to one hundred thousand times more potent in protecting the host from infections than the first. In vitro, their effects are also dramatically different from one another with only beta androstenetriol potentiating the cellular response by increasing lymphocyte activation and counteracting hydrocortisone immune-suppressive activity. Conceptually, the androstenes form a new and different subclass of steroid hormones with unique physiological properties. Following host injury, the balance between the epimers and isomers is a determining factor in the overall regulation of hematopoiesis, TH(l)/TH(2) balance, and host resistance to infections and tumor growth.
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PMID:Immune up-regulation and tumor apoptosis by androstene steroids. 1239 92

The heme biosynthetic pathway of the malaria parasite is a drug target and the import of host delta-aminolevulinate dehydratase (ALAD), the second enzyme of the pathway, from the red cell cytoplasm by the intra erythrocytic malaria parasite has been demonstrated earlier in this laboratory. In this study, ALAD encoded by the Plasmodium falciparum genome (PfALAD) has been cloned, the protein overexpressed in Escherichia coli, and then characterized. The mature recombinant enzyme (rPfALAD) is enzymatically active and behaves as an octamer with a subunit Mr of 46,000. The enzyme has an alkaline pH optimum of 8.0 to 9.0. rPfALAD does not require any metal ion for activity, although it is stimulated by 20-30% upon addition of Mg2+. The enzyme is inhibited by Zn2+ and succinylacetone. The presence of PfALAD in P. falciparum can be demonstrated by Western blot analysis and immunoelectron microscopy. The enzyme has been localized to the apicoplast of the malaria parasite. Homology modeling studies reveal that PfALAD is very similar to the enzyme species from Pseudomonas aeruginosa, but manifests features that are unique and different from plant ALADs as well as from those of the bacterium. It is concluded that PfALAD, while resembling plant ALADs in terms of its alkaline pH optimum and apicoplast localization, differs in its Mg2+ independence for catalytic activity or octamer stabilization. Expression levels of PfALAD in P. falciparum, based on Western blot analysis, immunoelectron microscopy, and EDTA-resistant enzyme activity assay reveals that it may account for about 10% of the total ALAD activity in the parasite, the rest being accounted for by the host enzyme imported by the parasite. It is proposed that the role of PfALAD may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite.
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PMID:Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported. 1463 82

In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.
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PMID:Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. 1671 89

Malaria is a leading cause of morbidity and mortality, estimated to cause >1 million childhood deaths annually. Plasmodium falciparum causes the most severe form of the disease. There is as yet no licensed vaccine for this disease, despite over a half century of research. In this study, we investigated a transmission-blocking vaccine candidate, the ookinete surface protein Pfs25. Antibodies against Pfs25, drawn in during a bite, can block parasite development in the mosquito midgut, preventing transmission to other individuals. Pfs25 is a low-molecular-weight protein, by itself not immunogenic. To increase its immunogenicity, we investigated several methods of conjugating Pfs25 to itself and to other proteins: recombinant Pseudomonas aeruginosa exotoxin A, and ovalbumin, using amide, hydrazone, or thioether linkages. All conjugates were immunogenic and induced booster responses in mice. The scheme to form amide bonds between proteins by using adipic acid dihydrizide as a linker produced the most immunogenic conjugates. Adsorption of the conjugates onto aluminum hydroxide further increased the antibody response. Remarkably, the antibody levels 3 or 7 months after the last injection were significantly higher than those 1 wk after that injection. The observed transmission-blocking activity of immune sera correlated with antibody levels measured by ELISA.
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PMID:Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. 1719 Jul 97

In recent supplement of neuroendocrinology letters, first time the authors from West and East, North and South of EU and the "Third World" present data on neuroinfections in high technology society - on nosocomial meningitis and vice versa in low technology and income countries of sub-Saharan Africa. 14 years survey of 171 cases of nosocomial paediatric meningitis is presented by Rudinsky et al. [1] and subpopulations of Acinetobacter baumannii and Pseudomonas aeruginosa [1,2] within last 20 years are briefly analyzed by Huttova et al. [2] and Ondrusova et al. [3]. All cases were complicating high technology procedures, such as neurosurgery, very low birth weight neonates after shunt implants etc. Current problems of management of nosocomial meningitis are reviewed by Bauer et al. [4] and consequence of inappropriate therapy by Huttova et al. [5]. Another high technology associated infection is septic embolisation followed by brain abscess and meningitis in patients with endocarditis after cardiac surgery (Kovac et al.) [6]. Experience from more than 600 cases is discussed in the article by Karvaj et al. [7] who outlines extremely high mortality in patients with endocarditis embolizing to central nervous system - up to 60%. The rest of papers are in contrary to problems of neuroinfections in EU and US focused on meningitis and cerebral malaria as commonest neuroinfections in the third world: 261 cases of cerebral malaria are discussed in a brief research note by Sudanese team of tropical programme in area of famine and civil war in southern Sudan (Bartkovjak and Ianetti et al.) [8]. Fungal neuroinfections complicating AIDS are of decreasing trend as reported by Njambi et al. from Kenya [9] and data from 497 cases from Uganda, Ethiopia and Burundi are presented by Benca et al. [10]. Finally an outbreak of meningococcal meningitis is reported by Benca et al. [11] from meningitis belt in Darfur and southern Sudan. We hope that the supplement may show difference in etiology, risk factors, therapy and outcome of neuroinfections (which is a burning public health and social problem in tropics) in other third world countries versus developed high-tech medical settings of US, EU and other high income countries, as presented by Benca et al. [12].
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PMID:Neuroinfections in developed versus developing countries. 1755 64

Some pathogenic bacteria produce factors that have evolved a capacity to neutralize competing microbes. The cupredoxin family protein azurin, produced by Pseudomonas aeruginosa, exhibits a remarkable ability to impede invasion of a number of diverse intracellular pathogens, including the human AIDS virus human immunodeficiency virus type 1 and the protozoan parasite Plasmodium falciparum (which causes malaria). Here we report that azurin and an azurin-like protein (Laz) from gonococci/meningococci have activity against Toxoplasma, an apicomplexan parasite that causes opportunistic infection in immunocompromised individuals. We demonstrate that the mechanism of action for Laz involves interfering with the ability of Toxoplasma to adhere to host cells. Computer structural analysis reveals that azurin shares structural features with the predominant surface antigen SAG1, which is known to play an important role in parasite attachment. Interestingly, azurin also has structural similarities to a monoclonal antibody to SAG1. Surface plasmon resonance binding studies validate that SAG1 interacts strongly with Laz and, to lesser extent, azurin. Moreover, Toxoplasma mutants lacking SAG1 are not as susceptible to the growth-inhibitory effects of Laz. Collectively, our data show that Toxoplasma adhesion can be significantly impaired by Laz, and to some extent by azurin, via interactions with SAG1. These observations indicate that Laz can serve as an important tool in the study of host-pathogen interactions and is worthy of further study for development into potential therapeutic agents.
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PMID:Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1. 1807 Sep 64

The presence of concomitant bacteria was assessed in the blood of 125 malaria positive patients and 60 malaria negative controls, resident in Owerri, southeastern Nigeria. Blood samples were cultured in MacConkey, Chocolate and Blood agar, respectively using oxoid signal system after the manufacturer's instructions. Blood cultures of 44 (35.2%) of the 125 malaria positive patients had bacterial growth while none was observed in the blood cultures of malaria negative patients. The bacteria species identified included: Staphylococcus aureus 4 (3.2%), Escherichia coli 3 (2.4%) Salmonella typhi 25 (20%), Klebsiella pneumoniae 10 (2.4%) and Pseudomonas aeruginosa 2 (1.6%). The presence of concomitant bacteria in malaria-positive cases usually results in persistence of malaria-like symptoms after treatment with antimalarials and subsequently taken as resistance of the parasites to the particular drugs in question. The significance of concomitant bacteria in the management of malaria should be given priority.
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PMID:Concomitant bacteria in the blood of malaria patients in Owerri, southeastern Nigeria. 1825 13


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