Urokinase enhances the growth of Pseudomonas spp. in vitro under nonshaking (oxygen limited) conditions

1994 ◽  
Vol 40 (4) ◽  
pp. 292-297 ◽  
Author(s):  
David A. Hart ◽  
Donald E. Woods

Urokinase is a proteinase that normally functions as a plasminogen activator. It is detected in a number of tissues and can be expressed by inflammatory cells such as macrophages and polymorphonuclear leucocytes. Addition of human urokinase to cultures of mucoid or nonmucoid variants of Pseudomonas aeruginosa (strain PAO and clinical isolates from patients with cystic fibrosis) or Pseudomonas cepacia incubated in a minimal medium under nonshaking (oxygen limited) conditions led to dose-dependent enhancement of bacterial growth. The enzyme exhibited a minimal effect on the growth of bacteria when cultured under more intense aeration conditions. This enhancement of bacterial growth by urokinase required the presence of active enzyme and was not detected with inactivated enzyme or noncatalytic domains of the enzyme. Enhancement of bacterial growth was not observed following incubation of P. aeruginosa with other proteinases including thrombin, neutrophil elastase, trypsin, chymotrypsin, or pseudomonas elastase and pseudomonas alkaline proteinase. Therefore, the observed effect of urokinase was relatively specific for this enzyme. As urokinase is a natural constituent of the lung, this enzyme could contribute to bacterial growth during pulmonary infections, particularly in an inflammatory environment in which the oxygen tension may be reduced.Key words: plasminogen activators, Pseudomonas aeruginosa, bacterial growth, urokinase, host proteinases.


2010 ◽  
Vol 54 (8) ◽  
pp. 3212-3218 ◽  
Author(s):  
Moshe Giladi ◽  
Yaara Porat ◽  
Alexandra Blatt ◽  
Esther Shmueli ◽  
Yoram Wasserman ◽  
...  

ABSTRACT High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2°C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality.



1995 ◽  
Vol 39 (4) ◽  
pp. 850-853 ◽  
Author(s):  
G M Eliopoulos ◽  
C B Wennersten ◽  
G Cole ◽  
D Chu ◽  
D Pizzuti ◽  
...  

This study evaluated the in vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent. The drug inhibited all tested members of the family Enterobacteriaceae at < or = 0.5 microgram/ml and all tested Pseudomonas aeruginosa, Burkholderia (Pseudomonas) cepacia, and Xanthomonas maltophilia strains at < or = 2 micrograms/ml. All but two strains of gram-positive bacteria were inhibited by < or = 1 microgram of the new drug per ml, including isolates highly resistant to ciprofloxacin.



2011 ◽  
Vol 111 (1) ◽  
pp. 245-254 ◽  
Author(s):  
P. Knezevic ◽  
D. Obreht ◽  
S. Curcin ◽  
M. Petrusic ◽  
V. Aleksic ◽  
...  


Author(s):  
Christian M. Gill ◽  
Adrian Brink ◽  
Chun Yat Chu ◽  
Jennifer Coetzee ◽  
George Dimopoulos ◽  
...  

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against mCIM-positive P. aeruginosa harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2g q8h HSR) and cefepime (2g and 1g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log 10 kill in all isolates. Cefepime activity was dose-dependent and MIC driven. This approach may be useful in assessing implications of β-lactamase variants.



2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Morgan T. Sutton ◽  
David Fletcher ◽  
Santosh K. Ghosh ◽  
Aaron Weinberg ◽  
Rolf van Heeckeren ◽  
...  

Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in thein vivomurine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness usingPseudomonas aeruginosa(gram negative bacteria) andStaphylococcus aureus(gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobialin vitroagainstPseudomonas aeruginosa, Staphylococcus aureus,andStreptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human,Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.



Chemotherapy ◽  
1995 ◽  
Vol 41 (5) ◽  
pp. 330-333 ◽  
Author(s):  
Robert C. Cohn ◽  
Lois Rudzienski ◽  
Robert W. Putnam


2001 ◽  
Vol 69 (7) ◽  
pp. 4521-4527 ◽  
Author(s):  
Stefan Worgall ◽  
Toshiaki Kikuchi ◽  
Ravi Singh ◽  
Katherine Martushova ◽  
Leah Lande ◽  
...  

ABSTRACT To develop a Pseudomonas aeruginosa vaccine that allows the host immune system to select the antigens, we hypothesized that dendritic cells (DC) pulsed with P. aeruginosa would induce protective immunity against pulmonary infections with P. aeruginosa. Incubation of murine bone marrow-derived DC with P. aeruginosa in vitro led to uptake of P. aeruginosa and activation of the DC. Spleen-derived CD4+ cells from mice immunized withP. aeruginosa-pulsed DC showed increased proliferation, demonstrating that DC pulsed with P. aeruginosa were capable of eliciting a P. aeruginosa-specific immune response. To evaluate if P. aeruginosa-pulsed DC can induce protective immunity against P. aeruginosapulmonary infection, DC incubated with P. aeruginosa in vitro were administered systemically to syngeneic mice, and the mice were then challenged by intrapulmonary infection with P. aeruginosa (5 × 104 CFU/mouse) 13 days later. Unimmunized control mice and mice who had previously received naive DC or DC stimulated with lipopolysaccharide or Escherichia coli died within 72 h. In contrast, 45% of mice receivingP. aeruginosa-pulsed DC demonstrated prolonged survival (>14 days). Finally, DC-pulsed with heat-inactivated P. aeruginosa protected CD8−/− but not CD4−/− mice, demonstrating that CD4+ T cells were required for the DC pulsed with P. aeruginosa to induce protective immunity.



2003 ◽  
Vol 47 (8) ◽  
pp. 2507-2512 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Morio Takema ◽  
Hideaki Miwa ◽  
Jingoro Shimada ◽  
Shogo Kuwahara

ABSTRACT The in vivo antibacterial activity of S-3578, a new parental cephalosporin, was compared with those of cefepime, ceftriaxone, ceftazidime, imipenem-cilastatin, and vancomycin. The efficacy of S-3578 against systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) SR3637 (50% effective dose [ED50], 7.21 mg/kg of body weight) was almost the same as that of vancomycin. In contrast, cefepime and imipenem-cilastatin were less active against this pathogen (ED50s, >100 and >100 mg/kg, respectively). S-3578 was the most effective compound against penicillin-resistant Streptococcus pneumoniae SR20946 (ED50, 1.98 mg/kg). S-3578 (10 mg/kg) induced a significant reduction in the numbers of viable MRSA SR17764 and Pseudomonas aeruginosa SR10396 organisms in polymicrobial pulmonary infections. The therapeutic efficacy of S-3578 was more potent than that of the combination of vancomycin and ceftazidime. High levels of S-3578 were detected in plasma in vivo, and its efficacy against experimentally induced infections in mice caused by MRSA and P. aeruginosa reflected its potent in vitro activity. We conclude that S-3578 is a promising new cephalosporin for the treatment of infections caused by gram-positive and -negative bacteria, including MRSA and P. aeruginosa.



1988 ◽  
Vol 29 (5) ◽  
pp. 589-592 ◽  
Author(s):  
F. Rasmussen ◽  
J. Georgsen ◽  
N. Grunnet

To evaluate the influence of radiographic contrast media (CM) on human polymorphonuclear leucocytes (PML), the ability of these cells to ingest latex particles after in vitro exposure to five different radiographic contrast media was investigated. All CM inhibited the phagocytic properties of PML. The inhibition was dose dependent. The inhibitory effect was partly due to hyperosmolality but CM specific inhibition was also evident.



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