Abstract
BackgroundCronobacter sakazakii is an emerging opportunistic bacterial pathogen known to cause neonatal and pediatric infections, including meningitis, necrotizing enterocolitis, and bacteremia. Multiple disease outbreaks of C. sakazakii have been documented in the past few decades, yet little is known of its genomic diversity, adaptation, and evolution. Here, we analyzed the pan-genome characteristics and phylogenetic relationships of 237 genomes of C. sakazakii and 48 genomes of related Cronobacter species isolated from diverse sources.ResultsThe C. sakazakii pan-genome contains 17,158 orthologous gene clusters, and approximately 19.5% of these constitute the core genome. Phylogenetic analyses reveal the presence of at least ten deep branching monophyletic lineages indicative of ancestral diversification. We detected enrichment of functions involved in proton transport and rotational mechanism in accessory genes exclusively found in human-derived strains. In environment-exclusive accessory genes, we detected enrichment for those involved in tryptophan biosynthesis and indole metabolism. However, we did not find significantly enriched gene functions for those genes exclusively found in food strains. The most frequently detected virulence genes are those that encode proteins associated with chemotaxis, enterobactin synthesis, ferrienterobactin transporter, type VI secretion system, galactose metabolism, and mannose metabolism. The genes fos which encodes resistance against fosfomycin, a broad-spectrum cell wall synthesis inhibitor, and mdf(A) which encodes a multidrug efflux transporter were found in nearly all genomes. We found that a total of 2991 genes in the pan-genome have had a history of recombination. Many of the most frequently recombined genes are associated with nutrient acquisition, metabolism and toxin production.ConclusionsOverall, our results indicate that the presence of a large accessory gene pool, ability to switch between ecological niches, a diverse suite of antibiotic resistance, virulence and niche-specific genes, and frequent recombination partly explain the remarkable adaptability of C. sakazakii within and outside the human host. These findings provide critical insights that can help define the development of effective disease surveillance and control strategies for Cronobacter-related diseases.
Highlights
Cronobacter sakazakii is an emerging opportunistic bacterial pathogen known to cause neonatal and pediatric infections, including meningitis, necrotizing enterocolitis, and bacteremia
We were interested in determining whether the species is genetically homogenous and if not, to what extent do distinct lineages differ and what processes contribute to this variation? We show that C. sakazakii is composed of several deep branching monophyletic lineages that vary in their core allelic and accessory gene content, including many antibiotic resistance and virulence genes
Our results indicate that the presence of a large accessory gene pool, ability to switch between ecological niches, a diverse suite of antibiotic resistance, virulence and niche-specific genes, and frequent recombination partly explain the remarkable adaptability of C. sakazakii to survive both within and outside the human host
Summary
Cronobacter sakazakii is an emerging opportunistic bacterial pathogen known to cause neonatal and pediatric infections, including meningitis, necrotizing enterocolitis, and bacteremia. We analyzed the pan-genome characteristics and phylogenetic relationships of 237 genomes of C. sakazakii and 48 genomes of related Cronobacter species isolated from diverse sources. Cronobacter sakazakii (family Enterobacteriaceae; class Gammaproteobacteria) is a motile, gram-negative, rodshaped opportunistic pathogen that is closely related to more well-known pathogenic genera such as Enterobacter and Citrobacter [1, 2]. C. sakazakii infections in neonates and immunocompromised infants are associated with clinical presentations of septicemia, meningitis, and necrotizing enterocolitis [13]. Even when infants survive the infection, different sequelae can potentially threaten their health, including developmental delays, hydrocephaly, and mental retardation [18]
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