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  • American Society for Microbiology  (35)
  • 1
    Online Resource
    Online Resource
    The Pseudomonas aeruginosa Autoinducer N -3-Oxododecanoyl Homoserine Lactone Accelerates Apoptosis in Macrophages and Neutrophils
    American Society for Microbiology ; 2003
    In:  Infection and Immunity Vol. 71, No. 10 ( 2003-10), p. 5785-5793
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 71, No. 10 ( 2003-10), p. 5785-5793
    Abstract: Quorum-sensing systems are critical regulators of the expression of virulence factors of various organisms, including Pseudomonas aeruginosa . Las and Rhl are two major quorum-sensing components, and they are regulated by their corresponding autoinducers, N -3-oxododecanoyl homoserine lactone (3-oxo-C 12 -HSL) and N -butyryl- l -homoserine lactone (C 4 -HSL). Recent progress has demonstrated the potential of quorum-sensing molecules, especially 3-oxo-C 12 -HSL, for modulation of the host immune system. Here we show the specific ability of 3-oxo-C 12 -HSL to induce apoptosis in certain types of cells. When bone marrow-derived macrophages were incubated with synthetic 3-oxo-C 12 -HSL, but when they were incubated not C 4 -HSL, significant loss of viability was observed in a concentration (12 to 50 μM)- and incubation time (1 to 24 h)-dependent manner. The cytotoxic activity of 3-oxo-C 12 -HSL was also observed in neutrophils and monocytic cell lines U-937 and P388D1 but not in epithelial cell lines CCL-185 and HEp-2. Cells treated with 3-oxo-C 12 -HSL revealed morphological alterations indicative of apoptosis. Acceleration of apoptosis in 3-oxo-C 12 -HSL-treated cells was confirmed by multiple criteria (caspases 3 and 8, histone-associated DNA fragments, phosphatidylserine expression). Structure-activity correlation experiments demonstrated that the fine structure of 3-oxo-C 12 -HSL, the HSL backbone, and side chain length are required for maximal activity. These data suggest that Pseudomonas 3-oxo-C 12 -HSL specifically promotes induction of apoptosis, which may be associated with 3-oxo-C 12 -HSL-induced cytotoxicity in macrophages and neutrophils. Our data suggest that the quorum-sensing molecule 3-oxo-C 12 -HSL has critical roles in the pathogenesis of P. aeruginosa infection, not only in the induction of bacterial virulence factors but also in the modulation of host responses.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.71.10.5785-5793.2003
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1483247-1
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  • 2
    Online Resource
    Online Resource
    Cloning and Sequencing of the Gene Encoding Toho-2, a Class A β-Lactamase Preferentially Inhibited by Tazobactam
    American Society for Microbiology ; 1998
    In:  Antimicrobial Agents and Chemotherapy Vol. 42, No. 5 ( 1998-05), p. 1181-1186
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 42, No. 5 ( 1998-05), p. 1181-1186
    Abstract: Escherichia coli TUM1083, which is resistant to ampicillin, carbenicillin, cephaloridine, cephalothin, piperacillin, cefuzonam, and aztreonam while being sensitive to cefoxitin, moxalactam, cefmetazole, ceftazidime, and imipenem, was isolated from the urine of a patient treated with β-lactam antibiotics. The β-lactamase (Toho-2) purified from the bacteria hydrolyzed β-lactam antibiotics such as penicillin G, carbenicillin, cephaloridine, cefoxitin, cefotaxime, ceftazidime, and aztreonam and especially had increased relative hydrolysis rates for cephalothin, cephaloridine, cefotaxime, and ceftizoxime. Different from other extended-spectrum β-lactamases, Toho-2 was inhibited 16-fold better by the β-lactamase inhibitor tazobactam than by clavulanic acid. Resistance to β-lactams was transferred by conjugation from E. coli TUM1083 to E. coli ML4909, and the transferred plasmid was about 54.4 kbp, belonging to the incompatibility group IncFII. The cefotaxime resistance gene for Toho-2 was subcloned from the 54.4-kbp plasmid. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 981 bases. The nucleotide sequence of the gene (DDBJ accession no. D89862 ) designated as bla toho was found to have 76.3% identity to class A β-lactamase CTX-M-2 and 76.2% identity to Toho-1. It has 55.9% identity to SHV-1 β-lactamase and 47.5% identity to TEM-1 β-lactamase. Therefore, the newly isolated β-lactamase designated as Toho-2 produced by E. coli TUM1083 is categorized as an enzyme similar to Toho-1 group β-lactamases rather than to mutants of TEM or SHV enzymes. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 327 amino acid residues. Comparison of Toho-2 with other β-lactamase (non-Toho-1 group) suggests that the substitutions of threonine for Arg-244 and arginine for Asn-276 are important for the extension of the substrate specificity.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.42.5.1181
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1998
    detail.hit.zdb_id: 1496156-8
    SSG: 12
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  • 3
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    Online Resource
    In Vitro Intracellular Activity and In Vivo Efficacy of Modithromycin, a Novel Bicyclolide, against Legionella pneumophila
    American Society for Microbiology ; 2011
    In:  Antimicrobial Agents and Chemotherapy Vol. 55, No. 4 ( 2011-04), p. 1594-1597
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 55, No. 4 ( 2011-04), p. 1594-1597
    Abstract: The in vitro and in vivo activities of modithromycin, a novel bicyclolide, against Legionella pneumophila were compared with those of telithromycin, clarithromycin, azithromycin, and levofloxacin. All the test agents decreased the intracellular growth of viable L. pneumophila bacteria over 96 h of incubation in both types of cells used, A/J mouse-derived macrophages and A549 human alveolar epithelial cells, at extracellular concentrations of 4× and 16× MIC, respectively. However, when the agents were removed from the medium after exposure for 2 h, regrowth of intracellular bacteria occurred in both cell systems when they were exposed to telithromycin, clarithromycin, and levofloxacin but not when they were exposed to modithromycin and azithromycin. Once-daily administration of modithromycin at a dose of 10 mg/kg of body weight for 5 days led to a significant decrease of intrapulmonary viable L. pneumophila bacteria in immunosuppressed A/J mice. The efficacy of modithromycin was superior to the efficacies of telithromycin and clarithromycin and comparable to the efficacies of azithromycin and levofloxacin. In addition, modithromycin and azithromycin inhibited the intrapulmonary regrowth of bacteria even at 72 h after the last treatment, but telithromycin and levofloxacin did not. These results suggested that modithromycin has longer-lasting cellular pharmacokinetic features like azithromycin. In conclusion, modithromycin, as well as azithromycin, has excellent in vitro and in vivo bactericidal activities and persistent efficacy against intracellular L. pneumophila . Modithromycin should be a useful agent for treatment of pulmonary infections caused by this pathogen.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01474-10
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1496156-8
    SSG: 12
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  • 4
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    Online Resource
    Extended-Spectrum-β-Lactamase-Producing Escherichia coli Strains Isolated from Farm Animals from 1999 to 2002: Report from the Japanese Veterinary Antimicrobial Resistance Monitoring Program
    American Society for Microbiology ; 2005
    In:  Antimicrobial Agents and Chemotherapy Vol. 49, No. 8 ( 2005-08), p. 3533-3537
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 49, No. 8 ( 2005-08), p. 3533-3537
    Abstract: A nationwide surveillance for antimicrobial susceptibility in Escherichia coli strains isolated from food-producing animals in Japan was conducted from 1999 to 2002. Eighteen cefazolin-resistant E. coli strains were isolated from broilers. Six were CTX-M-type producing, and eight were CMY-2 producing, while eight had mutations at the ampC promoter region.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.49.8.3533-3537.2005
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2005
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    In Vitro and In Vivo Antibacterial Activities of CS-834, a New Oral Carbapenem
    American Society for Microbiology ; 1998
    In:  Antimicrobial Agents and Chemotherapy Vol. 42, No. 3 ( 1998-03), p. 555-563
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 42, No. 3 ( 1998-03), p. 555-563
    Abstract: CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae , as well as Neisseria gonorrhoeae , Moraxella catarrhalis , the members of the family Enterobacteriaceae (with the exception of Serratia marcescens ), Haemophilus influenzae , and Bordetella pertussis ; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC 90 s) were 1.0 μg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens , Brukholderia cepacia , Stenotrophomonas maltophilia , and Acinetobacter calcoaceticus , R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC 90 s ranging from 2 to 〉 128 μg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.42.3.555
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1998
    detail.hit.zdb_id: 1496156-8
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    SSG: 15,3
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  • 6
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    Online Resource
    Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases
    American Society for Microbiology ; 2016
    In:  Antimicrobial Agents and Chemotherapy Vol. 60, No. 7 ( 2016-07), p. 4384-4386
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 7 ( 2016-07), p. 4384-4386
    Abstract: To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies ( k cat / K m ) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM −1 s −1 , respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.03098-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1496156-8
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  • 7
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    Online Resource
    Chromosomal Integration and Location on IncT Plasmids of the bla CTX-M-2 Gene in Proteus mirabilis Clinical Isolates
    American Society for Microbiology ; 2012
    In:  Antimicrobial Agents and Chemotherapy Vol. 56, No. 2 ( 2012-02), p. 1093-1096
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 56, No. 2 ( 2012-02), p. 1093-1096
    Abstract: Analysis of five CTX-M-2-producing Proteus mirabilis isolates in Japan demonstrated that bla CTX-M-2 was located on the chromosome in four isolates and on IncT plasmids in three isolates, including two isolates that also carried the gene on the chromosome. In all four isolates with chromosomal bla CTX-M-2 , IS Ecp1 was responsible for the integration of the gene into the chromosome. Three different sites in the P. mirabilis genomic sequence were utilized as integration sites.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00258-11
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2012
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    In Vitro Antibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci
    American Society for Microbiology ; 2011
    In:  Antimicrobial Agents and Chemotherapy Vol. 55, No. 4 ( 2011-04), p. 1588-1593
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 55, No. 4 ( 2011-04), p. 1588-1593
    Abstract: The in vitro activities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% of Streptococcus pneumoniae , Streptococcus pyogenes , and methicillin-susceptible Staphylococcus aureus (MSSA) strains, respectively. Modithromycin showed MIC 90 s of 0.125 μg/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin against ermB -carrying S. pyogenes was ≥32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence of mefA or mefE in both streptococci. Against Gram-negative pathogens, modithromycin showed MIC 90 s of 0.5, 8, and 0.031 μg/ml against Moraxella catarrhalis , Haemophilus influenzae , and Legionella spp., respectively. The MICs of modithromycin against M. catarrhalis and H. influenzae were higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti- Legionella activity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of the Legionella species.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01469-10
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 9
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    Online Resource
    Anti- Clostridium difficile Potential of Tetramic Acid Derivatives from Pseudomonas aeruginosa Quorum-Sensing Autoinducers
    American Society for Microbiology ; 2010
    In:  Antimicrobial Agents and Chemotherapy Vol. 54, No. 2 ( 2010-02), p. 683-688
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 54, No. 2 ( 2010-02), p. 683-688
    Abstract: We have examined the potential bactericidal activities of several tetramic acids derived from Pseudomonas autoinducers against Clostridium difficile , a cause of antibiotic-associated pseudomembranous colitis. Clinical isolates of C. difficile ( n = 4) were incubated in broth with a chemically synthesized Pseudomonas autoinducer and its tetramic acid derivatives. The structure-activity relationship and the mechanisms of action were examined by a time-killing assay and by determination of the morphological/staining characteristics. The use of some tetramic acids derived from N -3-oxododecanoyl l -homoserine lactone resulted in more than 3-log reductions in the viability of C. difficile within 30 min at 30 μM. The outer membrane was suggested to be one of the targets for the bactericidal activity of tetramic acid, because disturbance of the bacterial outer surface was demonstrated by alteration of the Gram-staining characteristic and electron microscopy. The data for the tetramic acid derivatives demonstrate that the keto-enol structure and the length of the acyl side chain of tetramic acid may be essential for the antibacterial activity of this molecule. These results suggest the potential for tetramic acid derivatives to be novel agents with activity against C. difficile .
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00702-09
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2010
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 10
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    Online Resource
    Role of a Mutation at Position 167 of CTX-M-19 in Ceftazidime Hydrolysis
    American Society for Microbiology ; 2004
    In:  Antimicrobial Agents and Chemotherapy Vol. 48, No. 5 ( 2004-05), p. 1454-1460
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 48, No. 5 ( 2004-05), p. 1454-1460
    Abstract: CTX-M-19 is a recently identified ceftazidime-hydrolyzing extended-spectrum β-lactamase, which differs from the majority of CTX-M-type β-lactamases that preferentially hydrolyze cefotaxime but not ceftazidime. To elucidate the mechanism of ceftazidime hydrolysis by CTX-M-19, the β-lactam MICs of a CTX-M-19 producer, and the kinetic parameters of the enzyme were confirmed. We reconfirmed here that CTX-M-19 is also stable at a high enzyme concentration in the presence of bovine serum albumin (20 μg/ml). Under this condition, we obtained more accurate kinetic parameters and determined that cefotaxime ( k cat /K m , 1.47 × 10 6 s −1 M −1 ), cefoxitin ( k cat /K m , 62.2 s −1 M −1 ), and aztreonam ( k cat /K m , 1.34 × 10 3 s −1 M −1 ) are good substrates and that imipenem ( k +2 /K , 1.20 × 10 2 s −1 M −1 ) is a poor substrate. However, CTX-M-18 and CTX-M-19 exhibited too high a K m value (2.7 to 5.6 mM) against ceftazidime to obtain their catalytic activity ( k cat ). Comparison of the MICs with the catalytic efficiency ( k cat /K m ) of these enzymes showed that some β-lactams, including cefotaxime, ceftazidime, and aztreonam showed a similar correlation. Using the previously reported crystal structure of the Toho-1 β-lactamase, which belongs to the CTX-M-type β-lactamase group, we have suggested characteristic interactions between the enzymes and the β-lactams ceftazidime, cefotaxime, and aztreonam by molecular modeling. Aminothiazole-bearing β-lactams require a displacement of the aminothiazole moiety due to a severe steric interaction with the hydroxyl group of Ser167 in CTX-M-19, and the displacement affects the interaction between Ser130 and the acidic group such as carboxylate and sulfonate of β-lactams.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.48.5.1454-1460.2004
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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