Abstract
BackgroundEscherichia coli is the most predominant Gram-negative bacterial pathogen associated with neonatal meningitis. Previous studies indicated that the prototypic neonatal meningitis E. coli (NMEC) strain RS218 (O18:K1:H7) harbors one large plasmid. Objectives of the present study were to analyze the complete nucleotide sequence of this large plasmid (pRS218) and its contribution to NMEC pathogenesis using in vitro and in vivo models of neonatal meningitis.ResultsThe plasmid is 114,231 bp in size, belongs to the incompatibility group FIB/IIA (IncFIB/IIA), and contains a genetic load region that encodes several virulence and fitness traits such as enterotoxicity, iron acquisition and copper tolerance. The nucleotide sequence of pRS218 showed a 41- 46% similarity to other neonatal meningitis-causing E. coli (NMEC) plasmids and remarkable nucleotide sequence similarity (up to 100%) to large virulence plasmids of E. coli associated with acute cystitis. Some genes located on pRS218 were overly represented by NMEC strains compared to fecal E. coli isolated from healthy individuals. The plasmid-cured strain was significantly attenuated relative to the RS218 wild-type strain as determined in vitro by invasion potential to human cerebral microvascular endothelial cells and in vivo by mortalities, histopathological lesions in the brain tissue, and bacterial recovery from the cerebrospinal fluid of infected rat pups.ConclusionsThe pRS218 is an IncFIB/IIA plasmid which shares a remarkable nucleotide sequence similarity to large plasmids of E. coli associated with cystitis. Both in vitro and in vivo experiments indicated that pRS218 plays an important role in NMEC pathogenesis.
Highlights
Escherichia coli is the most predominant Gram-negative bacterial pathogen associated with neonatal meningitis
These contigs were aligned to the reference plasmid sequence pUTI89 of uropathogenic E. coli strain UTI89 which was selected as the reference according to the sequence similarity of contigs (>90%)
Based on the blast analysis, nearly one third of the open reading frames (ORFs) (n = 51) represents the genes involved in plasmid replication and conjugal transfer, along with 20 and 7 genes encoding mobile genetic elements (MGEs) and products involved in DNA repair, respectively
Summary
Escherichia coli is the most predominant Gram-negative bacterial pathogen associated with neonatal meningitis. Genomic plasticity of E. coli is mainly due to the acquisition of ‘genomic islands’ through horizontal gene transfer by means of plasmids, phages and insertion sequences (IS) [9] Of these elements, bacterial plasmids are self-replicating extra-chromosomal genetic materials which have the potential to transmit a variety of phenotypic characteristics among the same or different species of bacteria [9,10,11]. Bacterial plasmids are self-replicating extra-chromosomal genetic materials which have the potential to transmit a variety of phenotypic characteristics among the same or different species of bacteria [9,10,11] These phenotypic characteristics include novel metabolic capabilities, antibiotic resistance, heavy metal tolerance, virulence traits that are important for bacterial adherence, invasion and survival in host tissues [10,11]. Plasmid that encodes such phenotypic characteristics may provide competitive advantages to the bacterium for survival and adaptation to novel niches
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