Abstract
Escherichia coli is the leading cause of Gram-negative neonatal septicemia in the United States. Invasion and passage across the neonatal gut after ingestion of maternal E. coli strains produce bacteremia. In this study, we compared the virulence properties of the neonatal E. coli bacteremia clinical isolate SCB34 with the archetypal neonatal E. coli meningitis strain RS218. Whole-genome sequencing data was used to compare the protein coding sequences among these clinical isolates and 33 other representative E. coli strains. Oral inoculation of newborn animals with either strain produced septicemia, whereas intraperitoneal injection caused septicemia only in pups infected with RS218 but not in those injected with SCB34. In addition to being virulent only through the oral route, SCB34 demonstrated significantly greater invasion and transcytosis of polarized intestinal epithelial cells in vitro as compared to RS218. Protein coding sequences comparisons highlighted the presence of known virulence factors that are shared among several of these isolates, and revealed the existence of proteins exclusively encoded in SCB34, many of which remain uncharacterized. Our study demonstrates that oral acquisition is crucial for the virulence properties of the neonatal bacteremia clinical isolate SCB34. This characteristic, along with its enhanced ability to invade and transcytose intestinal epithelium are likely determined by the specific virulence factors that predominate in this strain.
Highlights
Escherichia coli is the most common Gram-negative bacterium causing neonatal sepsis in the United States
Virulence of neonatal E. coli clinical isolates bacteremia was present in 14% and 39% of those infected with SCB34 or RS218, respectively (p = ns,S7 Table), and in none infected orally with DH5α
We have demonstrated that the E. coli clinical isolate SCB34 has the distinct ability to produce neonatal bacteremia after oral inoculation but not after IP injection, and to invade and transcytose intestinal epithelial cells more efficiently as compared to the archetypal neonatal meningitis isolate RS218
Summary
Escherichia coli is the most common Gram-negative bacterium causing neonatal sepsis in the United States. E. coli surpasses group B streptococcus as the most common cause of neonatal bacteremia in premature newborns and in otherwise normal febrile infants [1,2,3]. Virulence of neonatal E. coli clinical isolates [5]. There is currently no vaccine or any other preventive strategy to control neonatal E. coli sepsis. The incidence of this disease continues to increase and rising antibiotic resistance rates are a public health concern as well since this drastically limits treatment options [6]
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