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)

The diagnosis and treatment of pneumonia in mass gathering situations is a medical challenge, requiring prompt decision making and knowledge of the aetiology. We studied cases of pneumonia admitted to two hospitals during the 1994 pilgrimage (Hajj) season to Makkah. Sixty-four patients were enrolled in the study, of which 47 (75%) were men with a mean age of 63 years (range 21-91). Nearly all were from developing countries. Diagnosis was established in 46 patients (72%) with Mycobacterium tuberculosis being the commonest causative organism (20%), followed by gram-negative bacilli (18.8%). Streptococcus pneumoniae accounted for only 10%, with Legionella pneumophilia, Mycoplasma pneumoniae, and viruses accounting each for 6%. The main finding of this study is that M. tuberculosis is a common cause of pneumonia under these unusual "extreme circumstances". Its presentation was acute and indistinguishable from pyogenic pneumonia. Thirty-one per cent of tuberculous cases had upper lobe involvement, 54% lower lobe, and 15% multi-lobar. This was similar to the radiographic features in non-tuberculous pneumonia cases. All but one patient with tuberculosis recovered following the administration of first-line anti-tuberculous drugs. The total mortality was 17%. The preponderance of M. tuberculosis and Gram-negative bacteria over S. pneumoniae may reflect the prior use of amoxycillin and the effect of exhaustion, malnutrition, and old age.
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PMID:Tuberculosis is the commonest cause of pneumonia requiring hospitalization during Hajj (pilgrimage to Makkah). 966 41

In this retrospective study we aimed to assess the diagnostic yield of bronchoalveolar lavage (BAL) in kidney transplant patients who were suspected of having severe respiratory infection or in whom empirical antibiotic treatment had failed. All BAL procedures performed on kidney transplanted patients suspected of having respiratory infections between January 1, 1988 and July 31, 1996 were analyzed. BAL was carried out in the standard way and samples were sent for cytologic and bacteriologic study. Thirty-three patients with a mean age of 48.5 years were enrolled. All had been receiving immunosuppressive treatment and the mean time following transplantation was 320 days. Thirty-one had received antibiotic treatment before BAL. BAL was positive for 21 of the 33 patients (64%). Twenty-two pathogens were identified: 6 Pneumocystis carinii, 4 Cytomegalovirus, 3 Mycobacterium tuberculosis, 2 Aspergillus fumigatus, 2 Herpes simplex type I, 1 Streptococcus pneumoniae, 1 Staphylococcus aureus, 1 Streptococcus mitis, 1 Legionella pneumophila, 1 Legionella longbeachae. BAL was negative for 12 patients, of whom 8 were tentatively diagnosed of bacterial infection, 3 of acute pulmonary edema and one of pulmonary infarction. Based on the results, therapy was changed for 20 patients (61%), 19 (58%) because an unsuspected pathogen was identified and 1 because treatment could be simplified. The diagnostic yield of BAL is high (64%) in kidney transplant patients suspected of respiratory infection and is useful for managing such cases, as evidenced by the fact that a high proportion (19/33) of our patients were infected by pathogens not covered by empirical treatment.
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PMID:[Usefulness of bronchoalveolar lavage in the renal transplant patient with suspected respiratory infection]. 980 76

Phagocytic immune cells (particularly macrophages and neutrophils) take up and digest particles that have invaded our bodies. In doing so, they represent a very early line of defence against a microbial attack. During uptake, the particles are wrapped by a portion of the phagocyte's plasma membrane, and a new endocytic compartment, the phagosome, is formed. The typical fate of a phagosome is its fusion with lysosomes to yield a phagolysosome in which the particle is digested. Recent data show that some 'intracellular microorganisms' that can cause severe illnesses (tuberculosis, leprosy, legionnaire's disease and others) manage to reprogramme the host phagocytes not to deliver them to the lysosomal compartment. This probably results in increased survival of the pathogens. The analysis of the composition of such 'novel' compartments and research on the molecular mechanisms underlying the microbial interference with host cell functions are likely to yield important insights into: (1) which endocytic/phagocytic compartments phagocytes employ to handle ingested material in general; (2) how some pathogenic microorganisms can reprogramme the phagocytic pathway; and possibly (3) how infections caused by these microorganisms can be treated more effectively. Here, some studies are presented analysing which compartments intracellular pathogens inhabit and how microbes might be able to reprogramme their host cells.
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PMID:Reprogramming the phagocytic pathway--intracellular pathogens and their vacuoles (review). 985 8

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.
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PMID:In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. 1022 17

Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
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PMID:Mechanisms of phagocytosis in macrophages. 1035 69

Bacterial pathogens often subvert eukaryotic cellular processes in order to establish a replicative niche and evade host immunity. Inhibition of phagosome lysosome fusion is a strategy used by several intracellular bacteria that grow within mammalian cells. It was shown recently that Legionella pneumophila possesses a cytolytic activity that results from the insertion of pores in the macrophage membrane upon contact, and that this activity requires the dot/icm gene products, which are necessary for intracellular growth and phagosome trafficking. Other bacteria that inhibit phagosome lysosome fusion, such as Mycobacterium tuberculosis, demonstrate similar cytolytic activities, which suggests that formation of pores in the phagosome membrane may account for the defects observed in phagosome trafficking. In this study, we identify a new class of L. pneumophila mutant that retains the pore-forming activity found in virulent bacteria, but is defective in phagosome lysosome fusion inhibition and intracellular growth. These data indicate that cytolytic activity is not sufficient for L. pneumophila-induced alterations in phagosome trafficking. Rather, the pore may be a vehicle that facilitates delivery of bacterial-derived effector molecules to the host cell cytoplasm.
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PMID:Pore-forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. 1036 1

The in vitro antibacterial spectrum of gatifloxacin was compared with those of ciprofloxacin and ofloxacin. Gatifloxacin was two- to four-fold more potent than comparator quinolones against staphylococci, streptococci, pneumococci and enterococci (gatifloxacin MIC90s, < or =1 mg/L, except 4 mg/L against methicillin-resistant Staphylococcus aureus and Enterococcus faecium). Gatifloxacin was two-fold less potent than ciprofloxacin, and the same as or two-fold more potent than ofloxacin against Enterobacteriaceae (MIC90s, 0.06-0.5 mg/L against most members of the Enterobacteriaceae and < or =1 mg/L against Proteus/Morganella spp.). Relative to the comparator quinolones, gatifloxacin was two- to four-fold more potent against Providencia spp., and had good potency against Acinetobacter spp. (MIC90s, 0.25-1 mg/L). Gatifloxacin and ofloxacin had similar anti-pseudomonal potency, with corresponding MIC90s of 4, 8 and 0.25 mg/L for Pseudomonas aeruginosa, Pseudomonas fluorescens and Pseudomonas stutzeri, while ciprofloxacin had two- to eight-fold more potency. The three quinolones were equipotent against Burkholderia cepacia (MIC90s, 8 mg/L), but gatifloxacin was two-fold more potent against Stenotrophomonas maltophilia (MIC90, 4 mg/L). Gatifloxacin was highly potent (MIC90s, 0.03-0.06 mg/L) against Haemophilus influenzae, Legionella spp., Helicobacter pylori and had at least eight-fold better anti-chlamydial and anti-mycoplasma potency (gatifloxacin MIC90s, 0.13 mg/L). The higher quinolone MICs for ureaplasma (MIC90s, 4-8 mg/L) may be due to the acidic pH of the ureaplasma test medium, which antagonizes quinolones. Like other quinolones, gatifloxacin had poor potency against Mycobacterium avium-intracellulare, though it was eight- to 16-fold more potent against Mycobacterium tuberculosis (MIC90, 0.25 mg/L). Of the three quinolones, only gatifloxacin had activity against Bacteroides fragilis and Clostridium difficile. In summary, gatifloxacin is a broad-spectrum 8-methoxy fluoroquinolone that is more potent than ciprofloxacin and ofloxacin against Gram-positive bacteria, chlamydia, mycoplasma, mycobacteria and anaerobes.
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PMID:In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin. 1074 19

The intracellular human pathogens Legionella pneumophila and Mycobacterium tuberculosis reside in altered phagosomes that do not fuse with lysosomes and are only mildly acidified. The L. pneumophila phagosome exists completely outside the endolysosomal pathway, and the M. tuberculosis phagosome displays a maturational arrest at an early endosomal stage along this pathway. Rab5 plays a critical role in regulating membrane trafficking involving endosomes and phagosomes. To determine whether an alteration in the function or delivery of Rab5 could play a role in the aberrant development of L. pneumophila and M. tuberculosis phagosomes, we have examined the distribution of the small GTPase, Rab5c, in infected HeLa cells overexpressing Rab5c. Both pathogens formed phagosomes in HeLa cells with molecular characteristics similar to their phagosomes in human macrophages and multiplied in these host cells. Phagosomes containing virulent wild-type L. pneumophila never acquired immunogold staining for Rab5c, whereas phagosomes containing an avirulent mutant L. pneumophila (which ultimately fused with lysosomes) transiently acquired staining for Rab5c after phagocytosis. In contrast, M. tuberculosis phagosomes exhibited abundant staining for Rab5c throughout its life cycle. To verify that the overexpressed, recombinant Rab5c observed on the bacterial phagosomes was biologically active, we examined the phagosomes in HeLa cells expressing Rab5c Q79L, a fusion-promoting mutant. Such HeLa cells formed giant vacuoles, and after incubation with various particles, the giant vacuoles acquired large numbers of latex beads, M. tuberculosis, and avirulent L. pneumophila but not wild-type L. pneumophila, which consistently remained in tight phagosomes that did not fuse with the giant vacuoles. These results indicate that whereas Rab5 is absent from wild-type L. pneumophila phagosomes, functional Rab5 persists on M. tuberculosis phagosomes. The absence of Rab5 on the L. pneumophila phagosome may underlie its lack of interaction with endocytic compartments. The persistence of functional Rab5 on the M. tuberculosis phagosomes may enable the phagosome to retard its own maturation at an early endosomal stage.
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PMID:Deviant expression of Rab5 on phagosomes containing the intracellular pathogens Mycobacterium tuberculosis and Legionella pneumophila is associated with altered phagosomal fate. 1076 59

We have designed a universal PCR capable of amplifying a portion of the 16S rRNA gene of eubacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Mycobacterium tuberculosis, Legionella pneumophila, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, Proteus mirabilis, Haemophilus influenzae, and Neisseria meningitidis. The sizes of the amplified products from various bacteria were the same (996 bp), but the restriction patterns of most PCR products generated by HaeIII digestion were different. PCR products from S. aureus and S. epidermidis could not be digested by HaeIII but yielded different patterns when they were digested with MnlI. PCR products from S. pneumoniae, E. faecium, and E. faecalis yielded the same HaeIII digestion pattern but could be differentiated by AluI digestion. PCR products from E. coli, K. pneumoniae, S. marcescens, and E. cloacae also had the same HaeIII digestion pattern but had different patterns when digested with DdeI or BstBI. This universal PCR could detect as few as 10 E. coli or 250 S. aureus organisms. Compared with culture, the sensitivity of this universal PCR for detection and identification of bacteria directly from 150 cerebrospinal fluids was 92.3%. These results suggest that this universal PCR coupled with restriction enzyme analysis can be used to detect and identify bacterial pathogens in clinical specimens.
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PMID:Use of PCR with universal primers and restriction endonuclease digestions for detection and identification of common bacterial pathogens in cerebrospinal fluid. 1083 56

Rab7 is a small GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. Phagosomes containing inert particles have also been shown to transiently acquire Rab7 as they mature. Disruption in the pathway prior to the acquisition of Rab7 has been suggested as playing a role in the altered maturation of Mycobacterium bovis BCG phagosomes. As a first step to determine whether disruption in the delivery or function of Rab7 could play a role in the altered maturation of Legionella pneumophila and M. tuberculosis phagosomes, we have examined the distribution of wild-type Rab7 and the GTPase-deficient, constitutively active mutant form of Rab7 in HeLa cells infected with L. pneumophila or M. tuberculosis. We have found that the majority of L. pneumophila and M. tuberculosis phagosomes acquire relatively abundant staining for Rab7 and for the constitutively active mutant Rab7 in HeLa cells that overexpress these proteins. Nevertheless, despite acquisition of wild-type or constitutively active Rab7, both the L. pneumophila and the M. tuberculosis phagosomes continue to exhibit altered maturation as manifested by a failure to acquire lysosome-associated membrane glycoprotein 1. These results demonstrate that L. pneumophila and M. tuberculosis phagosomes have receptors for Rab7 and that the altered maturation of these phagosomes is not due to a failure to acquire Rab7.
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PMID:Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested maturation despite acquisition of Rab7. 1094 39


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