Author:
Mirza Kamran A.,Nietzsche Sandor,Makarewicz Oliwia,Pletz Mathias W.,Thieme Lara
Abstract
AbstractGalleria 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 (107 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 106 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 log10 CFU/larvae, while antibiotic treatment led to a 3 log10 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.
Funder
Friedrich-Schiller-Universität Jena
Publisher
Springer Science and Business Media LLC
Reference26 articles.
1. Tacconelli, E. et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 18, 318–327 (2018).
2. Halpin, A. L. et al. Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention. Am. J. Infect. Control 44, 830–836 (2016).
3. Ghose, C. et al. Clostridium difficile infection in the twenty-first century. Emerg. Microbes Infect. 2, 1–8 (2013).
4. Gordillo Altamirano, F. L. et al. Phage therapy in the postantibiotic era. Clin. Microbiol. Rev. 32, 10–1128 (2019).
5. Cao, F. et al. Evaluation of the efficacy of a bacteriophage in the treatment of pneumonia induced by multidrug resistance Klebsiella pneumoniae in mice. Biomed. Res. Int. 2015, 1–5 (2015).