Abstract
Design of phage cocktails as a harness against antimicrobial resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae
Glonti, Tea 1, PIRNAY, Jean-Paul 1
1Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium Background. Carbapenem-resistant K. pneumoniae and P. aeruginosa are an emerging cause of healthcare-associated infections that pose a significant threat to public health. These bacteria are difficult to treat due to their high level of resistance to antibiotics and their high mortality rate. Combating antimicrobial resistance is a key challenge for effective infection prevention and control, and recent advances in phage therapy support its potential as a tool (adjunct or alternative) to combat antimicrobial resistance and difficult-to-treat infections.
Materials. The approach presented here considers the development and use of assemblages of phages in 14 different cocktails and very diverse bacteria-kits (bacterial panels of a total of 257 strains for both species) with different genetic/biological profiles, including the resistotypes of P. aeruginosa and K. pneumoniae strains with different capsular serotypes and carbapenemase (KPC) producing strains. The developed "interpretation model" allows to monitor the phage-bacteria co-proliferation, the growth of phage resistant mutants (PRM) and to evaluate the mode of phage proliferation dynamics with bacteria: synergy, proto-cooperation or antagonism.
Results. 14 bacteriophage cocktails from different genera were designed and their lytic activities were tested in parallel on planktonic bacterial cultures with different virulence factors and MDRs (multidrug-resistant). Based on the results, the phage bi- and tri-cocktails performed well for the most part and inhibited the growth of PRM, resulting in a synergy or proto-cooperation. At least two of them showed in vitro killing activity against P. aeruginosa strains with the different virulence factors, including three resistotypes of PAO1, PA7 and PA14, and against K. pneumoniae strains with five different capsular serotypes (K1, K2, K27, K30, K62, K81) and one with KPC-3.
Conclusions. Phage virulence, the emergence of PRMs and their correlation with bacterial virulence and antibiotic resistance are of great importance for the therapeutic use of phages. The approach of using highly diverse bacteria-kits to assess phage virulence in relation to antibiotic-resistant strains and PRM emergence has been shown to facilitate the evaluation and differentiation of the therapeutic potential of individual phages and cocktails. It is incredibly efficient to use a large bacteria-kits of different virulence factors and MDRs to design relevant cocktails to target other AMR bacterial strains to ensure their efficacy against clinically significant pathogens. This study supports the potential of phage cocktails in the control of MDR pathogens.
Glonti, Tea 1, PIRNAY, Jean-Paul 1
1Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium Background. Carbapenem-resistant K. pneumoniae and P. aeruginosa are an emerging cause of healthcare-associated infections that pose a significant threat to public health. These bacteria are difficult to treat due to their high level of resistance to antibiotics and their high mortality rate. Combating antimicrobial resistance is a key challenge for effective infection prevention and control, and recent advances in phage therapy support its potential as a tool (adjunct or alternative) to combat antimicrobial resistance and difficult-to-treat infections.
Materials. The approach presented here considers the development and use of assemblages of phages in 14 different cocktails and very diverse bacteria-kits (bacterial panels of a total of 257 strains for both species) with different genetic/biological profiles, including the resistotypes of P. aeruginosa and K. pneumoniae strains with different capsular serotypes and carbapenemase (KPC) producing strains. The developed "interpretation model" allows to monitor the phage-bacteria co-proliferation, the growth of phage resistant mutants (PRM) and to evaluate the mode of phage proliferation dynamics with bacteria: synergy, proto-cooperation or antagonism.
Results. 14 bacteriophage cocktails from different genera were designed and their lytic activities were tested in parallel on planktonic bacterial cultures with different virulence factors and MDRs (multidrug-resistant). Based on the results, the phage bi- and tri-cocktails performed well for the most part and inhibited the growth of PRM, resulting in a synergy or proto-cooperation. At least two of them showed in vitro killing activity against P. aeruginosa strains with the different virulence factors, including three resistotypes of PAO1, PA7 and PA14, and against K. pneumoniae strains with five different capsular serotypes (K1, K2, K27, K30, K62, K81) and one with KPC-3.
Conclusions. Phage virulence, the emergence of PRMs and their correlation with bacterial virulence and antibiotic resistance are of great importance for the therapeutic use of phages. The approach of using highly diverse bacteria-kits to assess phage virulence in relation to antibiotic-resistant strains and PRM emergence has been shown to facilitate the evaluation and differentiation of the therapeutic potential of individual phages and cocktails. It is incredibly efficient to use a large bacteria-kits of different virulence factors and MDRs to design relevant cocktails to target other AMR bacterial strains to ensure their efficacy against clinically significant pathogens. This study supports the potential of phage cocktails in the control of MDR pathogens.
| Original language | English |
|---|---|
| Title of host publication | ESCMID/ASM Conference |
| Publisher | ESCMID/ASM |
| Publication status | Published - 14 Sept 2024 |