Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0026936 (Mycoplasma)
14,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attempted allelic replacement of 144 Streptococcus pneumoniae open reading frames of previously uncharacterized function led to the identification of 36 genes essential for growth under laboratory conditions. Of these, 14 genes (obg, spoIIIJ2, trmU, yacA, yacM, ydiC, ydiE, yjbN, yneS, yphC, ysxC, ytaG, yloI and yxeH4) were also essential in Staphylococcus aureus and Haemophilus influenzae or Escherichia coli, 2 genes (yrrK and ydiB) were only essential in H. influenzae as well as S. pneumoniae and 8 genes were necessary for growth of S.pneumoniae and S. aureus and did not have a homolog in H. influenzae(murD2, ykqC, ylqF, yqeH, ytgP, yybQ) or were not essential in that organism (yqeL, yhcT). The proteins encoded by these genes could represent good targets for novel antibiotics covering different therapeutic profiles. The putative functions of some of these essential proteins, inferred by bioinformatic analysis, are presented. Four mutants, with deletions of loci not essential for in vitro growth, were found to be severely attenuated in a murine respiratory tract infection model, suggesting that not all targets for antibacterial therapeutics are revealed by simple in vitro essentiality testing. The results of our experiments together with those collated from previously reported studies including Bacillus subtilis, E. coli and Mycoplasma sp. demonstrate that gene conservation amongst bacteria does not necessarily indicate that essentiality in one organism can be extrapolated to others. Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results.
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PMID:A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown function. 1504 29

Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial's antibacterial spectrum must include the most likely pathogens: Streptococcus pneumoniae, the most frequent cause of community-acquired pneumonia (CAP), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, as well as atypicals such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila (Chlamydia) pneumoniae. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC > or =2 mg/l) among isolates of S. pneumoniae varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility--including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12-1 mg/l)--is frequently found in association with macrolide resistance, which is found at a prevalence of 70-80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is beta-lactamase production among isolates of H. influenzae and M. catarrhalis. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.
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PMID:Comparative antimicrobial susceptibility of respiratory tract pathogens. 1531 48

Community-acquired pneumonia (CAP) is the sixth most common cause of death in the United States and the leading cause of death from infectious diseases. It is associated with significant morbidity and mortality, and poses a major economic burden to the healthcare system. Streptococcus pneumoniae is the leading cause of CAP. Other common bacterial causes include Haemophilus influenzae as well as atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species). Increasing resistance to a variety of antimicrobial agents has been documented in S. pneumoniae and is common in H. influenzae as well. Successful empiric therapy is paramount to the management of CAP to avoid treatment failure and subsequent associated costs. Given that resistance is increasing among respiratory pathogens, and S. pneumoniae is the most common etiologic agent identified in CAP, strategies for antimicrobial therapy should be based on the likely causative pathogen, the presence of risk factors for infection with resistant bacteria, and local resistance patterns.
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PMID:Streptococcus pneumoniae and community-acquired pneumonia: a cause for concern. 1536 96

We developed a diagnostic array of oligonucleotide probes targeting species-specific variable regions of the genes encoding topoisomerases GyrB and ParE of respiratory bacterial pathogens. Suitable broad-range primer sequences were designed based on alignment of gyrB/parE sequences from nine different bacterial species. These species included Corynebacterium diphtheriae, Fusobacterium necrophorum, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. Specific probe sequences were selected by comparative analysis against the European Bioinformatics Database, as well as gyrB/parE sequences generated for this study. To verify specificity, at least six initial oligonucleotide probe sequences per bacterial species were tested by hybridization on a solid glass support using culture collection strains as templates. Finally, three oligonucleotide probes per bacterial species were utilized to examine 65 middle ear fluid and 29 throat swab samples. The sensitivities of the developed assay compared to classic culture from middle ear fluid samples for H. influenzae, M. catarrhalis, and S. pneumoniae were 96 (93 for culture), 73 (93 for culture), and 100% (78% for culture), respectively. No cross-reactivity with bacterial species belonging to the normal oral flora was observed when the 29 throat swab samples were studied. The sensitivity of the assay to detect S. pyogenes from these samples was 93% (80% for culture). These results provide a proof of concept for the diagnostic use of microarray technology based on broad-range topoisomerase gene amplification, followed by hybridization and specific detection of bacterial species.
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PMID:Use of an oligonucleotide array for laboratory diagnosis of bacteria responsible for acute upper respiratory infections. 1536 22

A multiplex PCR (mPCR) was developed for simultaneous detection of specific genes for Streptococcus pneumoniae (lytA), Mycoplasma pneumoniae (P1), Chlamydophila pneumoniae (ompA), and Haemophilus influenzae (16S rRNA, with verification PCR for P6). When the protocol was tested on 257 bacterial strains belonging to 37 different species, no false negatives and only one false positive were noted. One Streptococcus mitis out of thirty was positive for lytA. In a pilot application study of 81 sputum samples from different patients with suspected lower respiratory tract infection (LRTI), mPCR identified S. pneumoniae in 25 samples, H. influenzae in 29, M. pneumoniae in 3, and C. pneumoniae in 1. All samples culture positive for S. pneumoniae (n=15) and H. influenzae (n=15) were mPCR positive for the same bacteria. In a pilot control study with nasopharyngeal swabs and aspirates from 10 healthy adults, both culture and mPCR were negative. No PCR inhibition was found in any of the mPCR-negative sputum or nasopharyngeal samples. Whether all samples identified as positive by mPCR are truly positive in an aetiological perspective regarding LRTI remains to be evaluated in a well-defined patient material. In conclusion, the mPCR appears to be a promising tool in the aetiological diagnostics of LRTI.
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PMID:Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae to be used on sputum samples. 1572 84

The steady-state serum and intrapulmonary pharmacokinetic and pharmacodynamic parameters of tigecycline were determined after intravenous administration in 30 subjects. Tigecycline was administered as a 100mg loading dose followed by six 50mg doses given every 12h and was measured using HPLC/mass spectrometry. Ratios of tigecycline maximum serum concentration and area under the serum concentration-time curve to 90%-minimum inhibitory concentrations (C(max)/MIC(90); AUC/MIC(90)), and percentage time above MIC(90) were calculated for common respiratory pathogens (Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). The C(max) (mean+/-S.D.), AUC and half-life for serum were 0.72+/-0.24 microg/mL, 1.73+/-0.64 microg*h/mL and 15.0+/-1.10h; for lung epithelial lining fluid (ELF) the values were 0.37 microg/mL, 2.28 microg*h/mL and 39.1h; and for alveolar cells (AC) were 15.2 microg/mL, 134 microg*h/mL and 23.7h. Tigecycline was concentrated in AC: C(max)/MIC(90) ratios ranged from 30.4 (H. influenzae) to 507 (S. pneumoniae); AUC/MIC(90) ratios ranged from 268 (H. influenzae) to 4467 (S. pneumoniae); and percentage dose interval above MIC(90) was 100% for the five respiratory pathogens. The C(max)/MIC(90), AUC/MIC(90) ratios, T>MIC(90) and extended serum and intrapulmonary half-lives following the regimen used in this study are favourable for the treatment of tigecycline-susceptible pulmonary infections.
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PMID:Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. 1588 87

Telithromycin, a recently approved ketolide antibiotic derived from 14-membered macrolides, is active against erythromycin-resistant pneumococci. Telithromycin has enhanced activity in vitro because it binds not only to domain V of ribosomal RNA (like macrolides do) but also to domain II. However, it is not active against streptococci and staphylococci with constitutive macrolide, lincosamide, and streptogramin B resistance. Telithromycin, available in an oral formulation, is approved by the US Food and Drug Administration for use in adults for treatment of (1) community-acquired pneumonia due to Streptococcus pneumoniae (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, or Mycoplasma pneumoniae; (2) acute exacerbation of chronic bronchitis due to S. pneumoniae, H. influenzae, or M. catarrhalis; or (3) acute bacterial sinusitis due to S. pneumoniae, H. influenzae, M. catarrhalis, or methicillin- and erythromycin-susceptible Streptococcus aureus. It is not approved for treatment of tonsillitis, pharyngitis, or severe pneumococcal pneumonia. Unique visual adverse effects occurred in 0.27%-2.1% of patients receiving telithromycin therapy. Its enhanced activity against some common respiratory pathogens makes it a valuable addition to the available macrolides.
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PMID:Telithromycin: a ketolide antibiotic for treatment of respiratory tract infections. 1588 65

In this study, real-time PCR with pathogen-specific molecular beacons (MB) and primers was evaluated for prediction of community-acquired pneumonia (CAP) causative agents, detecting six main CAP agents, Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and Streptococcus pyogenes, simultaneously. The PCR assay was evaluated for fresh clinical specimens from infants and children (n = 389) and from adults (n = 40). The MB probes and primers are both pathogen specific, namely, the lytA gene for S. pneumoniae, the mip gene for L. pneumophila, and 16S rRNA genes for the remaining four organisms. DNA extraction of clinical specimens was performed with a commercially available EXTRAGEN II kit, and amplification was performed with Stratagene Mx3000P. The limit of detection for these pathogens ranged from 2 copies to 18 copies. The whole process from DNA extraction to the analysis was finished in less than 2 h. The obtained sensitivity and specificity of this real-time PCR study relative to those of conventional cultures were as follows: 96.2% and 93.2% for S. pneumoniae, 95.8% and 95.4% for H. influenzae, 100% and 100% for S. pyogenes, and 100% and 95.4% for M. pneumoniae, respectively. The sensitivity and specificity for M. pneumoniae relative to those of a serologic assay were 90.2% and 97.9%, respectively. In six clinical samples of C. pneumoniae, the real-time PCR gave positive predictable values, and in those cases, elevation of the titer value was also observed. In conclusion, we demonstrated that a real-time PCR assay with pathogen-specific MB is useful in identifying CAP causative agents rapidly and in examining the clinical course of empirical chemotherapy in a timely manner, supporting conventional culture methods.
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PMID:Simultaneous detection of pathogens in clinical samples from patients with community-acquired pneumonia by real-time PCR with pathogen-specific molecular beacon probes. 1659 74

Although a wide variety of recognized pathogens causes community-acquired pneumonia, the precise etiology in Japan remains unknown. We prospectively investigated the etiology in 232 patients with community-acquired pneumonia who visited 20 community-general hospitals. New diagnostic methods, using polymerase chain reaction (PCR) assays and urinary antigen tests were employed, in addition to conventional methods. The frequency of identification of causative pathogens was high (73.3%), and the leading organism was Streptococcus pneumoniae (24.6%), followed by Haemophilus influenzae (18.5%), viruses (16.4%), Chlamydia pneumoniae (6.5%), Mycoplasma pneumoniae (5.2%), and Legionella spp. (3.9%). S. pneumoniae and M. pneumoniae were the most prevalent pathogens in younger patients, and S. pneumoniae and H. influenzae were the most prevalent in elderly patients. Multiple or mixed infections were found in 25.9% of all patients and in 35.3% with a causal diagnosis. The results have important practical implications for the initial treatment of adult patients with community-acquired pneumonia.
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PMID:Prospective multicenter study of the causative organisms of community-acquired pneumonia in adults in Japan. 1664 44

The present study assessed the diagnostic usefulness of a multiplex PCR (mPCR) for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae applied to bronchoalveolar lavage (BAL). Fibreoptic bronchoscopy was performed on 156 hospitalised adult patients with lower respiratory tract infection (LRTI) and 36 controls. BAL fluid was analysed with bacterial culture and mPCR. By conventional diagnostic methods, S. pneumoniae, H. influenzae, M. pneumoniae and C. pneumoniae were aetiological agents in 14, 21, 3.2 and 0% of the LRTI patients, respectively. These pathogens were identified by BAL mPCR in 28, 47, 3.2 and 0.6% of cases, respectively, yielding sensitivities of 86% for S. pneumoniae, 88% for H. influenzae, 100% for M. pneumoniae and 0% for C. pneumoniae, and specificities of 81, 64, 100 and 99% for S. pneumoniae, H. influenzae, M. pneumoniae and C. pneumoniae, respectively. Of the 103 patients who had taken antibiotics prior to bronchoscopy, S. pneumoniae was identified by culture in 2.9% and by mPCR in 31%. Among the controls, mPCR identified S. pneumoniae in 11% and H. influenzae in 39%. In lower respiratory tract infection patients, bronchoalveolar lavage multiplex PCR can be useful for identification of Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydophila pneumoniae. The method appears to be particularly useful in patients treated with antibiotics.
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PMID:Evaluation of a multiplex PCR for bacterial pathogens applied to bronchoalveolar lavage. 1673 90


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