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Published on: October 27, 2013
Three novel Enterobacter cloacae bacteriophages for therapeutic use from Ghanaian natural waters
O L Lyytinen1, C Dapuliga2, D Wallinger3
1Human Microbiome Research Program (HUMI), Faculty of Medicine, University of Helsinki, Helsinki, Finland. outi.lyytinen@helsinki.fi.
Abstract:
Infections caused by multidrug-resistant (MDR) bacteria are a growing global concern. Enterobacter cloacae complex (ECC) species are particularly adept at developing antibiotic resistance. Phage therapy is proposed as an alternative treatment for pathogens that no longer respond to antibiotics. Unfortunately, ECC phages are understudied when compared to phages of many other bacterial species. In this Ghanaian-Finnish study, we isolated two ECC strains from ready-to-eat food samples and three novel phages from natural waters against these strains. We sequenced the genomic DNA of the novel Enterobacter phages, fGh-Ecl01, fGh-Ecl02, and fGh-Ecl04, and assessed their therapeutic potential. All of the phages were found to be lytic, easy to propagate, and lacking any toxic, integrase, or antibiotic resistance genes and were thus considered suitable for therapy purposes. They all were found to be related to T4-type viruses: fGh-Ecl01 and fGh-Ecl04 to karamviruses and fGh-Ecl02 to agtreviruses. Testing of Finnish clinical ECC strains showed promising susceptibility to these novel phages. As many as 61.1% of the strains were susceptible to fGh-Ecl01 and fGh-Ecl04, and 7.4% were susceptible to fGh-Ecl02. Finally, we investigated the susceptibility of the newly isolated ECC strains to three antibiotics - meropenem, ciprofloxacin, and cefepime - in combination with the novel phages. The use of phages and antibiotics together had synergistic effects. When using an antibiotic-phage combination, even low concentrations of antibiotics fully inhibited the growth of bacteria.
Insights
Novel bacteriophages effective against multidrug-resistant Enterobacter cloacae complex (ECC) were identified. These phages show promise for phage therapy, especially when combined with antibiotics, offering a new strategy against resistant bacterial infections.
Area of Science:
- Microbiology
- Genetics
- Therapeutics
Background:
- Multidrug-resistant (MDR) bacterial infections, particularly from Enterobacter cloacae complex (ECC), pose a significant global health threat.
- Phage therapy is an emerging alternative for treating antibiotic-resistant pathogens, but ECC phages remain understudied.
Purpose of the Study:
- To isolate and characterize novel bacteriophages targeting ECC strains.
- To evaluate the therapeutic potential of these phages, individually and in combination with antibiotics.
Main Methods:
- Isolation of ECC strains and novel phages from food and water samples.
- Genomic sequencing of isolated phages (fGh-Ecl01, fGh-Ecl02, fGh-Ecl04).
- Assessment of phage lytic activity, genetic makeup (absence of toxic/resistance genes), and efficacy against clinical ECC strains and in combination with antibiotics.
Main Results:
- Three novel, lytic phages (fGh-Ecl01, fGh-Ecl02, fGh-Ecl04) were isolated and characterized, showing no toxic or antibiotic resistance genes.
- Phages demonstrated susceptibility against 61.1% (fGh-Ecl01, fGh-Ecl04) and 7.4% (fGh-Ecl02) of tested Finnish clinical ECC strains.
- Combined phage-antibiotic treatment exhibited synergistic effects, enabling full bacterial growth inhibition with low antibiotic concentrations.
Conclusions:
- Novel bacteriophages against ECC are suitable for therapeutic use.
- Phage therapy, especially in combination with antibiotics, presents a potent strategy against multidrug-resistant ECC infections.
