Experimental protection of diabetic mice against Lethal P. aeruginosa infection by bacteriophage
Nagaveni Shivshetty1, Rajeshwari Hosamani1, Liyakat Ahmed2
1Department of Biotechnology, Gulbarga University, Gulbarga, Karnataka 585106, India.
Abstract:
The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistant P. aeruginosa. P. aeruginosa was used to induce septicemia in streptozotocin (STZ) induced diabetic and nondiabetic mice by intraperitoneal (i.p.) injection of 3 × 10(8) CFU, resulting in a fatal bacteremia within 48 hrs. A single i.p. injection of 3 × 10(9) PFU phage GNCP showed efficient protection in both diabetic (90%) and nondiabetic (100%) bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4 h and 6 h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20 h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 10(9) PFU/mL) was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against pernicious P. aeruginosa infections, especially in cases of immunocompromised host.
Insights
Bacteriophage therapy offers a promising alternative to antibiotics for treating multidrug-resistant Pseudomonas aeruginosa infections. Phage GNCP demonstrated high efficacy in protecting both diabetic and nondiabetic mice against lethal bacterial challenge.
Area of Science:
- Microbiology
- Infectious Diseases
- Therapeutic Strategies
Background:
- Antibiotic resistance in bacterial strains presents a significant global health challenge.
- Multidrug-resistant Pseudomonas aeruginosa infections require novel therapeutic approaches.
- Bacteriophage therapy is an emerging alternative for combating bacterial infections.
Purpose of the Study:
- To evaluate the efficacy of bacteriophage GNCP against multidrug-resistant Pseudomonas aeruginosa.
- To assess the effectiveness of phage therapy in both diabetic and nondiabetic mouse models of septicemia.
- To compare phage therapy with conventional antibiotic treatment.
Main Methods:
- Induction of fatal Pseudomonas aeruginosa septicemia in diabetic and nondiabetic mice via intraperitoneal injection.
- Administration of a single dose of bacteriophage GNCP (3 × 10^9 PFU) at various time points post-infection.
- Comparison of protection rates and survival outcomes between phage-treated and imipenem-treated groups.
Main Results:
- A single intraperitoneal injection of phage GNCP provided 90% protection in diabetic mice and 100% in nondiabetic mice against lethal Pseudomonas aeruginosa challenge.
- Therapeutic efficacy decreased in diabetic mice when phage administration was delayed beyond 4-6 hours.
- Nondiabetic mice showed protection even when phage treatment was delayed up to 20 hours.
- Phage GNCP demonstrated superior effectiveness compared to multiple doses of imipenem.
Conclusions:
- Bacteriophage therapy is highly effective against Pseudomonas aeruginosa infections, including in immunocompromised hosts.
- Phage therapy presents a viable alternative to antibiotics for treating multidrug-resistant bacterial infections.
- Timely administration of bacteriophages is crucial for optimal therapeutic outcomes, particularly in diabetic individuals.
