Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila, an intracellular bacterial pathogen whose capacity to multiply in human mononuclear phagocytes is dependent upon the availability of intracellular iron. In view of this, we have studied the effects of chloroquine and ammonium chloride on L. pneumophila intracellular multiplication in human monocytes. Chloroquine, at a concentration of 20 microM, and ammonium chloride, at a concentration of 20 mM, inhibited L. pneumophila intracellular multiplication by 1.4 +/- 0.2 (SEM) logs and 1.5 +/- 0.2 logs, respectively. Chloroquine- and ammonium chloride-induced inhibition of L. pneumophila intracellular multiplication was completely reversed by iron nitrilotriacetate, an iron compound which is soluble in the neutral to alkaline pH range, but not by iron transferrin, which depends upon acidic intracellular conditions to release iron. Chloroquine had no major direct effect on L. pneumophila multiplication in artificial media except at extremely high concentrations (15,000-fold that which inhibited L. pneumophila multiplication in mononuclear phagocytes), and inhibition at such concentrations was not reversed by iron nitrilotriacetate. This study demonstrates that chloroquine and ammonium chloride inhibit the intracellular multiplication of L. pneumophila by limiting the availability of iron to the bacterium. It is possible that such a mechanism of action underlies chloroquine's antimicrobial effect against other intracellular pathogens, such as the agents of malaria and tuberculosis.
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PMID:Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. 205 29

Gene htpB, which encodes the 58-kilodalton protein of Legionella pneumophila, was cloned in Escherichia coli and its complete nucleotide sequence was determined. Analysis of this sequence revealed an open reading frame of 1,644 nucleotides encoding a protein with a predicted molecular mass of 57,952 daltons. Data obtained by amino-terminal sequencing of the purified 58-kilodalton protein agreed, except for one amino acid residue, with the predicted amino acid sequence, identifying this open reading frame as htpB. A comparison of the primary structure of this protein to other proteins of similar molecular weights from E. coli, Mycobacterium leprae, M. tuberculosis, and Coxiella burnetii revealed significant regions of sequence similarity, which are discussed.
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PMID:Nucleotide sequence of htpB, the Legionella pneumophila gene encoding the 58-kilodalton (kDa) common antigen, formerly designated the 60-kDa common antigen. 211 82

A 60-kilodalton (kDa) immunodominant antigen of Legionella pneumophila is a heat shock protein (HSP) of the GroEL class of HSPs. The gene (htpB) coding the 60-kDa protein was localized to a 3.2-kilobase DNA fragment of L. pneumophila cloned into pUC19 (pSH16) (P. S. Hoffman, C. A. Butler, and F. D. Quinn, Infect. Immun. 57:1731-1739, 1989). The nucleotide sequence of the DNA fragment cloned into M13 confirmed two open reading frames, htpA and htpB, that code for proteins of 96 and 548 amino acids, respectively. A consensus heat shock promoter sequence upstream of the start of htpA was identified, and no obvious promoter sequences were detected upstream of htpB. Amino acid sequence comparison studies revealed that the L. pneumophila HtpB protein exhibited 76% homology with the 65-kDa protein of Mycobacterium tuberculosis and 85% homology with both GroEL of Escherichia coli and HtpB of Coxiella burnetii. A comparison of the amino acid sequences among these proteins revealed several regions of nearly absolute sequence conservation, with the variable regions occurring in common areas. The purified L. pneumophila 60-kDa protein was antigenic for human T lymphocytes. Indirect fluorescent antibody studies indicated that the 60-kDa protein may be located in the periplasm or expressed on the surface by intracellular bacteria, suggesting that a stress-related mechanism may be involved in the expression of this immunodominant antigen.
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PMID:Legionella pneumophila htpAB heat shock operon: nucleotide sequence and expression of the 60-kilodalton antigen in L. pneumophila-infected HeLa cells. 220 80

Although animal models of infection are associated with certain limitations in interpretation, properly performed studies provide important information for evaluating the efficacy of new antimicrobial agents in the treatment of human disease. The antibacterial efficacy of the newer quinolones, particularly ciprofloxacin, has undergone extensive evaluation in several animal models. Efficacy has been demonstrated in animal models of pneumonia, endocarditis, meningitis, skin and soft-tissue infections, septic arthritis, burn wound sepsis, empyema, intra-abdominal abscess, osteomyelitis, prostatitis, sinusitis, urinary tract infection, chronic gastroenteritis, granuloma pouch infection, and Pseudomonas septicemia. More recent studies have evaluated the efficacy of ciprofloxacin in animal models of tuberculosis and syphilis, as well as in infections caused by the intracellular pathogens Salmonella typhimurium, Legionella pneumophila, and Listeria monocytogenes.
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PMID:An update on the efficacy of ciprofloxacin in animal models of infection. 258 79

To assess the prevalence of Legionnaires' disease, 115 patients with 'difficult-to-treat' chest infections were screened for Legionnella pneumophila. The results were positive in 10 (37%) of 27 patients with pulmonary tuberculosis, 15 (22%) of 68 with a recent onset acute respiratory infection, and 7 (35%) of 20 patients with history of a chronic respiratory infection. These 32 patients were enrolled in an open therapeutic trial of erythromycin. Less severe cases (17 of 32) received erythromycin stearate orally (500 mg 4-times daily) for up to 28 days, while severe cases were treated for the first few days with intravenous erythromycin lactobionate (4 g/day). Weekly chest X-ray examinations revealed prompt resolution. Most patients had no signs and symptoms detectable after 7 days, and none persisted up to 28 days. There were no therapeutic failures and microbiological tests on Day 28 were negative for Legionella pneumophila. It is suggested that the possibility of co-existing legionellosis should be considered in all patients with difficult to treat acute and chronic chest infections, particularly in developing countries where tuberculosis is very common, and treatment instituted or supplemented with erythromycin as the drug of choice.
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PMID:Acute and chronic Legionnaires' disease and co-existent tuberculosis: a trial of erythromycin. 268 Feb 87

In addition to providing a powerful approach for identifying bacterial factors required for full infectivity and disease production, genetic analysis of Legionella pathogenesis should also lend critical insight into the biology of the macrophage and into the pathogenesis of other intracellular parasites. The interaction between L. pneumophila and the macrophage exhibits many features found in a wide variety of prokaryotic and eukaryotic intracellular human pathogens. For example, binding to complement receptors has been shown to occur for Mycobacterium tuberculosis, M. leprae, Leishmania donovani, Leishmania major and Histoplasma capsulatum. Coiling phagocytosis has been observed during entry of L. donovani. Phagosomes that contain Toxoplasma gondii or M. tuberculosis fail to fuse with lysosomes and, in the case of T. gondii, have been shown to remain close to neutral pH. Although the molecular bases for these phenomena are unknown, their functional similarities to the L. pneumophila-macrophage interaction provide optimism that generally applicable principles are involved. The genetic techniques reviewed here will provide the molecular tools with which such questions of a general biologic nature can be framed and eventually answered. Together with more traditional methods in biochemistry, microbiology and cell biology, molecular genetics offers a robust means toward identifying and understanding the bacterial factors involved in the pathogenesis of Legionnaires' disease. Molecular studies of L. pneumophila can also help address questions concerning the epidemiology, diagnosis and prevention of disease. For example, the distribution of virulence factors might help explain and predict the attack rates of different L. pneumophila strains or Legionella species. Moreover, bacterial genes/factors that are shown to be conserved in Legionella strains could be used to develop such diagnostic tools as DNA probes. Novel types of vaccines consisting of genetically constructed, avirulent L. pneumophila strains or subunit vaccines based on the molecular characterization of virulence factors might be developed and tested as protective immunogens. In this way, the capacity to analyze and to manipulate L. pneumophila genetically may facilitate the use of Legionnaires' disease as a model infection for studying protective cell-mediated immunity. Apart from its clinical significance as the etiologic agent of Legionnaires' disease, L. pneumophila may be a key to broader understandings in microbial pathogenesis and human cell biology and immunology. Although the extremely complex processes of bacterial infection and virulence are best understood when a variety of experimental approaches are employed, we believe that the evolving molecular genetic techniques reviewed here will be critical elements in many important breakthroughs in the future.
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PMID:Genetics and molecular pathogenesis of Legionella pneumophila, an intracellular parasite of macrophages. 269 60

In a one-year prospective study of 106 adults (mean age, 60 years) who were admitted to hospital with community-acquired pneumonia, an aetiological diagnosis was made in 82 (77%) patients. Streptococcus pneumoniae was considered to be responsible for 44 (42%) and respiratory viruses for 19 (18%) infections. Other aetiological agents that were found in a smaller number of patients included Haemophilus influenzae (9% of patients), enteric Gram-negative bacilli (8% of patients), Staphylococcus aureus (3% of patients), Legionella spp. (3% of patients), Mycobacterium tuberculosis (3% of patients), Mycoplasma pneumoniae (8% of patients) and Chlamydia psittaci (5% of patients). The mortality was 10% and was related significantly to increasing age and to coexisting heart and lung disease. Antibiotic treatment that was commenced before admission to hospital and investigations were undertaken reduced significantly the isolation rate of susceptible bacterial pathogens. The Gram-stained smear of sputum was valuable in establishing a tentative diagnosis of bacterial pneumonia. The most-useful tests in making an early diagnosis proved to be those which detected pneumococcal and mycoplasmal antigens, blood cultures and culture of sputum for appropriate bacterial pathogens.
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PMID:A prospective hospital study of the aetiology of community-acquired pneumonia. 273 13

In acquired immunodeficiency syndrome (AIDS) the pulmonary opportunistic infections are due to the depression of cellular immunity and they are found in more than 50% of patients. Most frequently the infection is due to Pneumocystis carinii, Cytomegalovirus, Cryptococcus neoformans and Mycobacterium avium-intracellulare. Non-opportunistic infections in AIDS are mostly due to the Mycobacterium tuberculosis and Legionella pneumophila. In Kaposi sarcoma in AIDS the lungs may be involved into pulmonary manifestations of the syndrome. In this paper the diagnostics of pulmonary disturbances in AIDS is briefly evaluated together with the therapy of most frequent pulmonary infections.
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PMID:[Pulmonary manifestations in patients with AIDS]. 279 62

The acquired immunodeficiency syndrome (AIDS) is a devastating new disease caused by the human immunodeficiency virus (HIV). This retrovirus causes profound immunoincompetence in its infected hosts, who are thereafter susceptible to develop myriad severe and relapsing protozoal, fungal, bacterial, viral, and arthropodal opportunistic infections, as well as unusual malignancies. The more than 50,000 patients who have developed AIDS in the United States have produced a sudden unexpected deluge of diagnostic dilemmas that are stressing laboratories of pathology everywhere. This paper describes the gross and microscopic pathology of the numerous complications in patients infected by HIV: (a) the prodromal AIDS-related complex with persistent generalized lymphadenopathy, (b) lymphoid infiltration of salivary gland and lung, including the complex of lymphoid interstitial pneumonitis-pulmonary lymphoid hyperplasia, (c) extranodal non-Hodgkin's lymphomas, (d) multifocal mucocutaneous and visceral Kaposi's sarcoma, (e) small cell undifferentiated (oat cell) carcinomas, (f) protozoal infections caused by Pneumocystis carinii, Toxoplasma gondii, Acanthamoeba, Cryptosporidium species (sp.), and Isospora belli, (g) the causes of chronic enteritis, (h) mycotic infections caused by Candida sp., Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, and Sporothrix schenckii, (i) bacterial infections caused by Mycobacterium avium-intracellulare, M. tuberculosis, M. kansasii, Nocardia sp., Listeria monocytogenes, Legionella sp., Treponema pallidum, and others, (j) viral infections caused by cytomegalovirus, herpes simplex and zoster, polyomavirus (progressive multifocal leukoencephalopathy), hepatitis B, molluscum contagiosum, and papillomavirus, (k) oral hairy leukoplakia, (l) subacute encephalopathy, and (m) Norwegian scabies.
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PMID:The pathology of AIDS. 283 78

Mixed bacterial pneumonia caused by organisms other than anaerobes has been infrequently reported. We describe six cases and review the literature. Two patients had co-infection with S pneumoniae and L pneumophila. Two were infected with S pneumoniae and K pneumoniae and the others simultaneously harbored M tuberculosis and N asteroides. The first two sets of patients had bacteria isolated from usually sterile sites (blood and lung), while the latter harbored repeatedly isolated organisms not usually felt to be part of the normal respiratory flora. Mixed infection may help explain the substantial mortality still seen from pneumonia. This is especially true if Legionella, mycobacteria, or Nocardia species are encountered where routine smears and cultures may not aid in the diagnosis. Poor clinical response to specific antibacterial therapy in pneumonia should trigger further investigation for other potential pathogens.
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PMID:Community-acquired pneumonia caused by mixed aerobic bacteria. 309 44


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