Showing papers by "Kazuhiro Tateda published in 2006"
TL;DR: In this paper, the authors reported that mouse macrophages restricted Legionella pneumophila replication and initiated a proinfl ammatory program of cell death when fl agellin contaminated their cytosol.
Abstract: To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinfl ammatory program of cell death when fl agellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1�� secretion were triggered by type IV secretioncompetent bacteria that encode fl agellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble fi laments, fl agellin triggered cell death but native fl agellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5 + macrophages restricted the growth of virulent microbes, but fl agellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5 + mice, the yield of L. pneumophila in the lungs declined, whereas the burden of fl agellin mutants increased. Accordingly, macrophages respond to cytosolic fl agellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinfl ammatory cytokines that control L. pneumophila infection.
504 citations
TL;DR: It is demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden.
Abstract: Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that Pseudomonas N-3-oxododecanoyl-l-homoserine lactone (3-oxo-C12-homoserine lactone, 3-oxo-C12-HSL), but not N-butanoyl-l-homoserine lactone (C4-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C12-HSL–carrier protein conjugate on acute P. aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12-HSL–BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3×106 c.f.u. P. aeruginosa PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)-α in the immunized mice were significantly lower than those of control mice (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated apoptosis in macrophages in vitro. These results demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.
103 citations
TL;DR: The synthesis of the analogs of N-3-oxodododecanoyl-L-homoserine lactone and their structure-activity relationship for the apoptotic induction in macrophages, P388D1 cells, is described and it was revealed that the position of the oxo group in the acyl side chain in addition to the presence of the L-homological unit is crucial for the programmed death-inducing activity.
39 citations
TL;DR: ‘Break-point Checkerboard Plate’ is reported, in which breakpoint concentrations were combined in a microtiter plate with 8 antibiotics, including carbapenem, aminoglycoside and fluoroquinolone, and demonstrated a strong synergistic effect of some antibiotic combinations at clinically relevant concentrations.
Abstract: Increase of multiple drug resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in the clinical setting. Although the checkerboard method to determine FIC index and synergistic effe...
37 citations
TL;DR: Qualitative analysis of urinary antigen may be a useful indicator for severity of disease and course of S. pneumoniae pneumonia and kinetics of antigen titer determination in urine and serum are analyzed, which may be crucial not only for diagnostic measures, but also may provide a better understanding of the pathogenesis of S.
Abstract: Detection of urinary antigen by a rapid immunochromatographic membrane test (Binax NOW) was widely accepted as a powerful tool for diagnosis of Streptococcus pneumoniae pneumonia. This is a qualitative kit, so the value of quantitative analysis of urinary antigen, especially correlation of antigen titers and severity of diseases, remained to be determined. We examined semi-quantitative antigen titer in urines collected from urinary antigen-proven S. pneumoniae pneumonia on admission, and analyzed the kinetics of antigen titer and its relation to severity of diseases. After serial 2-fold dilution of urine, the highest dilution for positive results was determined, and this was designated as maximum dilution factor (MDF). MDFs varied from 1 to 4096 in 29 patients examined (mean MDF, 317.8). Importantly, severe cases of S. pneumoniae pneumonia were higher values of MDFs (mean MDF: 760.5) than those of non-severe cases (mean MDF: 5.4). The patients with high MDFs (≥64) demonstrated higher values of LDH, CRP an...
27 citations
TL;DR: This study shows that it is possible to identify these physiologically atypical S. aureus isolates correctly by using the Phoenix and AutoScan-4 fully automatic identification systems.
Abstract: Between January and April 2002, a total of 271 strains of Staphylococcus aureus were isolated from clinical specimens at Toho University Omori Hospital, Japan, including 201 (74.2 %) which were identified as meticillin-resistant S. aureus (MRSA). However, 34 (12.5 %) were biochemically atypical, because they did not produce acid on mannitol salt agar or did not agglutinate in Staphaurex testing but were categorized as MRSA by PCR analysis and by antibiotic susceptibility. Three automatic identification systems, AutoScan-4 (Dade Behring), BD Phoenix (Becton Dickinson) and Vitek 2 (bioMerieux), were evaluated by testing these atypical S. aureus isolates. The AutoScan-4 and Phoenix systems identified all 34 isolates as S. aureus. Without additional tests such as Staphaurex, observation of colony pigment and haemolysins on sheep blood agar, Vitek 2 identified only 16 isolates (47.1 %) as S. aureus with good or better confidence levels and misidentified one of the remaining isolates as Staphylococcus chromogenes. This study shows that it is possible to identify these physiologically atypical S. aureus isolates correctly by using the Phoenix and AutoScan-4 fully automatic identification systems.
19 citations