Phage resistance in Klebsiella pneumoniae and bidirectional effects impacting antibiotic susceptibility.
Clin Microbiol Infect
; 30(6): 787-794, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38522841
ABSTRACT
OBJECTIVES:
Bacteriophage (phage) therapy is a promising anti-infective option to combat antimicrobial resistance. However, the clinical utilization of phage therapy has been severely compromised by the potential emergence of phage resistance. Although certain phage resistance mechanisms can restore bacterial susceptibility to certain antibiotics, a lack of knowledge of phage resistance mechanisms hinders optimal use of phages and their combination with antibiotics.METHODS:
Genome-wide transposon screening was performed with a mutant library of Klebsiella pneumoniae MKP103 to identify phage pKMKP103_1-resistant mutants. Phage-resistant phenotypes were evaluated by time-kill kinetics and efficiency of plating assays. Phage resistance mechanisms were investigated with adsorption, one-step growth, and mutation frequency assays. Antibiotic susceptibility was determined with broth microdilution and population analysis profiles.RESULTS:
We observed a repertoire of phage resistance mechanisms in K pneumoniae, such as disruption of phage binding (fhuATn and tonBTn), extension of the phage latent period (mnmETn and rpoNTn), and increased mutation frequency (mutSTn and mutLTn). Notably, in contrast to the prevailing view that phage resistance re-sensitizes antibiotic-resistant bacteria, we observed a bidirectional steering effect on bacterial antibiotic susceptibility. Specifically, rpoNTn increased susceptibility to colistin while mutSTn and mutLTn increased resistance to rifampicin and colistin.DISCUSSION:
Our findings demonstrate that K pneumoniae employs multiple strategies to overcome phage infection, which may result in enhanced or reduced antibiotic susceptibility. Mechanism-guided phage steering should be incorporated into phage therapy to better inform clinical decisions on phage-antibiotic combinations.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Bacteriófagos
/
Pruebas de Sensibilidad Microbiana
/
Klebsiella pneumoniae
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
Clin Microbiol Infect
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia