title: Galleria mellonella infection model demonstrates high lethality of ST69 and ST127 uropathogenic E. coli.
abstract: Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae within 24 hours. Interestingly, ST131 isolates were the least virulent. We observed that ST127 isolates are significantly associated with a higher VF-score than isolates of all other STs tested (P≤0.0001), including ST69 (P<0.02), but one ST127 isolate (strain EC18) was avirulent. Comparative genomic analyses with virulent ST127 strains revealed an IS1 mediated deletion in the O-antigen cluster in strain EC18, which is likely to explain the lack of virulence in the larvae infection model. Virulence in the larvae was not correlated with serotype or phylogenetic group. This study illustrates that G. mellonella are an excellent tool for investigation of the virulence of UPEC strains. The findings also support our suggestion that the incidence of ST127 strains should be monitored, as these isolates have not yet been widely reported, but they clearly have a pathogenic potential greater than that of more widely recognised clones, including ST73, ST95 or ST131.
authors: Microbiology and Virology Unit, School of Medicine, University of Manchester, Manchester, United Kingdom; King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors: Majed F
authors: MF
authors: Alghoribi
authors: Microbiology and Virology Unit, School of Medicine, University of Manchester, Manchester, United Kingdom.
authors: Tarek M
authors: TM
authors: Gibreel
authors: Central Manchester Foundation Trust, Manchester, United Kingdom.
authors: Andrew R
authors: AR
authors: Dodgson
authors: Australian Infectious Disease Centre, School of Chemistry & Molecular Biosciences, University of Queensland, Queensland, Australia.
authors: Scott A
authors: SA
authors: Beatson
authors: Microbiology and Virology Unit, School of Medicine, University of Manchester, Manchester, United Kingdom; School of Biomedical and Healthcare Science, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.
authors: Mathew
authors: M
authors: Upton
mesh_terms: D000818:Animals; D003141:Communicable Diseases / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007814:Larva / Q000235:genetics / Q000382:microbiology*; D007915:Lepidoptera / Q000235:genetics / Q000382:microbiology*; D019081:O Antigens / Q000235:genetics; D065288:Serogroup; D056689:Uropathogenic Escherichia coli / Q000145:classification / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D019081:O Antigens