Bacteriophage-mediated decolonization of Klebsiella pneumoniae in a novel Galleria mellonella gut colonization model with Enterobacteriaceae

• Published in: Scientific reports 2024-01, Vol.14 (1), p.318-318, Article 318
• Main Authors: Mirza, Kamran A., Nietzsche, Sandor, Makarewicz, Oliwia, Pletz, Mathias W., Thieme, Lara
• Format: Article
• Language: English
• Subjects: 631/326; 631/326/1321; 631/326/22; 631/326/41; 631/326/421; 692/699/255; Animals; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacteria; Bacteriophages; Ciprofloxacin; Colonization; Decolonization; Digestive system; E coli; Enterobacteriaceae; Escherichia coli; Force-feeding; Galleria mellonella; Gastrointestinal tract; Humanities and Social Sciences; Intestinal microflora; Klebsiella pneumoniae; Larva - microbiology; Larvae; Mammals; Meropenem; Microbiomes; Moths - microbiology; multidisciplinary; Phages; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-50823-9

Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (10 7 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 10 6  CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log 10 CFU/larvae, while antibiotic treatment led to a 3 log 10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models.