Introducing 

Prezi AI.

Your new presentation assistant.

Refine, enhance, and tailor your content, source relevant images, and edit visuals quicker than ever before.

Loading…
Transcript

Follow

MATERIALS AND METHODS

Bacteriophage Can Treat and Prevent Pseudomonas aeruginosa Lung Infections

Laurent Debarbieux,1 Dominique Leduc,2 Damien Maura,1 Eric Morello,1 Alexis Criscuolo,1 Olivier Grossi,3 Viviane Balloy,2 and Lhousseine Touqui2

Of preparing student

MADA Ali

MARAM Ateq

MONERAH Fares

* Pulmonary infections are one of the major causes of mortality worldwide. Each year it is estimated that 2 million children 5 years old die of acute respiratory infections .

* * Furthermore, the number of bacterial infections is probably increasing because of resistance to antibiotics. Opportunistic pathogens are becoming increasingly resistant to multiple antibiotics, which

urges us to seek other therapeutic approaches

Antibiotic-resistant bacteria threaten life worldwide. Although new antibiotics are scarce, the use of bacteriophage, viruses that infect bacteria, is rarely proposed as a means of offsetting this shortage.

  • injection of a mixture of ketamine-xylazine before being infected.

  • The infectious dose was luminescent bacteria resuspended in 50 mL of PBS. then 2 h after
  • bacterial instillation the bioluminescence was recorded and 30mL of bacteriophages were applied intranasally while the mice
  • (isofluorane inhalation).
  • In preventive experiments, 24 h before infection the animals received intranasally 30 mL of bacteriophages or PBS while under a light anesthesia Luminescence measurements.

  • Photon emission of the luminescent bacteria in the lungs of infected mice false-color photon emission image was generated, and photons were counted within a constant-defined area corresponding to
  • the surface of the chest and encompassing the whole lung region

NOTS

Target

Pseudomonas aeruginosa strain, we monitored and quantified the efficacy of a bacteriophage treatment

in mice during acute lung infection. Bacteriophage treatment not only was effective in saving animals

from lethal infection, but also was able to prevent lung infection when given 24 h before bacterial infection, thereby extending the potential use of bacteriophages as therapeutic agents to combat bacterial lung infection .

References

RESULTS

Three main characteristics distinguish bacteriophage therapy from antibiotic therapy:

(1) bacteriophages multiply at the infection site;

(2) they target only specific bacteria, with no effect on commensal flora

(3) they can adapt to resistant bacteria.

The bacterium Pseudomonas aeruginosa causes acute pneumonia with a high mortality rate in immunocompromised patients; in patients with cystic fibrosis (CF), it triggers chronic inflammation that leads to destruction of the lungs

Timing of the bacteriophage treatment. We next determined

the maximum possible delay of bacteriophage treatment

to maintain an animal survival rate of 100% by administering

treatment at 2, 4, or 6 h after infection. Although 100% of

mice survived in the group treated with phages 2 h after infection,

at 24 h only 75% of mice were still alive in the groups

treated 4 or 6 h after infection. At 72 h

Figure 1. Effect of bacteriophage treatment on deadly infection in

mice. Survival curves of infected animals treated with phosphatebuffered saline (PBS) or bacteriophages at indicated bacteriophage-tobacterium

The amount of bacteria required to induce a deadly lung infection in Balb

MATERIALS AND METHODS

Dose- and time-dependent effect of bacteriophages on infected mice. We isolated from sewage water a bacteriophage specific to the PAK strain of P. aeruginosa was designed to determine the amount of this bacteriophage required to fully cure infected mice . Although non– phage-treated mice died within 48 h after inoculation with PAK (most of them were still alive after 24 h), mice treated with bacteriophages in a phage-to-bacterium ratio of 1:10 died within 5 days after inoculation with PAK. Mice treated with

higher bacteriophage-to-bacterium ratios (1:1 and 10:1) survived until the end of the experiment and their behavior was monitored for 10 days. These mice did not show erratic behavior, their fur remained regular,

and they gained weight, which suggests that the bacteriophage solution had no adverse affect on them.

P. aeruginosa strains.

  • The bioluminescent PAK strain used in this study has been described elsewhere
  • We obtained 10 primary colonization strains and 10 chronic colonization strains of P. aeruginosa
  • Bacteriophage isolation, preparation, and characterization For the animal experiments .
  • Electron microscopic analysis was performed

these results clearly open the possibility of using bacteriophages in the prevention of bacterial lung infections. For example, one possibility is pretreatment of populations at risk for such infections (immunocompromised patients or patients with cystic fibrosis) to decrease the probability of infection in places where patients are more likely to be infected by bacteria . This is particularly relevant in situations in which an epidemic strain has been identified and for which preventive treatment with specific . In conclusion, our work supports the potential use of bacteriophagesto fight pathogens involved in lung infections and to develop an application to prevent such infections from occurring. Moreover, with the use of bioluminescent bacteria it is now possible to compare several bacteriophages

1. Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of

world-wide distribution of child deaths from acute respiratory infections.

Lancet Infect Dis 2002; 2:25–32.

2. Walsh C. Where will new antibiotics come from? Nat Rev Microbiol

2003; 1:65–70.

3. Merril CR, Scholl D, Adhya SL. The prospect for bacteriophage therapy

in Western medicine. Nat Rev Drug Discov 2003; 2:489–497.

4. Brussow H. Phage therapy: the Escherichia coli experience. Microbiology

2005; 151:2133–2140.

5. Barrow PA, Soothill JS. Bacteriophage therapy and prophylaxis:

rediscovery

and renewed assessment of potential. Trends Microbiol 1997;

5:268–271.

DISCUSSION

Acknowledgments

Our experiments demonstrate that noninvasive bioluminescence

technology is remarkably useful for assessing the efficacy

of bacteriophage treatment and especially for studying infection

kinetics at early time points without sacrificing animals.

Thank you for your kind attention

I would like to thank my friends who participated in the work of all those who helped me in accomplished, and I hope you enjoyed this offer

Learn more about creating dynamic, engaging presentations with Prezi