Abstract
Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients. E. bugandensis (EB-247) is a recently described species of Enterobacter, associated with neonatal sepsis. Here we demonstrate that the extended spectrum ß-lactam (ESBL) producing isolate EB-247 is highly virulent in both Galleria mellonella and mouse models of infection. Infection studies in a streptomycin-treated mouse model showed that EB-247 is as efficient as Salmonella Typhimurium in inducing systemic infection and release of proinflammatory cytokines. Sequencing and analysis of the complete genome and plasmid revealed that virulence properties are associated with the chromosome, while antibiotic-resistance genes are exclusively present on a 299 kb IncHI plasmid. EB-247 grew in high concentrations of human serum indicating septicemic potential. Using whole genome-based transcriptome analysis we found 7% of the genome was mobilized for growth in serum. Upregulated genes include those involved in the iron uptake and storage as well as metabolism. The lasso peptide microcin J25 (MccJ25), an inhibitor of iron-uptake and RNA polymerase activity, inhibited EB-247 growth. Our studies indicate that Enterobacter bugandensis is a highly pathogenic species of the genus Enterobacter. Further studies on the colonization and virulence potential of E. bugandensis and its association with septicemic infection is now warranted.
Highlights
Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients
We characterized and determined the complete genome of a representative strain of new Enterobacter species, i.e. E. bugandensis EB-247 isolated from a pediatric intensive care unit
Infection experiments with G. mellonella demonstrated that EB-247 was more pathogenic than E. cloacae ATCC 13047, which is the most virulent E. cloacae strain known, and was as pathogenic as S
Summary
Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients. Enterobacter infections can include bacteremia, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections (UTIs), endocarditis, intra-abdominal infections, septic arthritis, osteomyelitis, CNS and ophthalmic- infections[1] They are of clinical importance as nosocomial opportunistic pathogens, being increasingly associated with neonatal sepsis and infections in immunocompromised hosts leading to bloodstream infections[2]. Studies with other enterobacterial species, in particular, Escherichia coli, have uncovered properties that contribute to bacterial survival in adverse host environments[10]. This has been much less studied in Enterobacter spp. so far
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