Pan-genome diversification and recombination in Cronobacter sakazakii, an opportunistic pathogen in neonates, and insights to its xerotolerant lifestyle

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.

Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

“…The resulting correlation pro le exhibited a monotonic decay ( Figure 5B), indicating the presence of recombination. Similar decaying correlation pro les have also been shown in other recombining bacteria, such as Helicobacter pylori, Pseudomonas aeruginosa, Salmonella enterica and Cronobacter sakazakii [63][64][65]. Meanwhile, the mcorr showed the mean fragment size (f̅ ) of a recombination event in M. luteus species was 874.45 bp; the recombination coverage (c), which indicates the proportion of sites in the genome whose diversity has come from recombination events since its last common ancestor, was 0.46; and the ratio γ/μ, the relative rate of recombination to mutation, was 10.87 ( Figure 5C).…”

Genomic Landscape and Phenotypic Assessment of Cronobacter sakazakii Isolated From Raw Material, Environment, and Production Facilities in Powdered Infant Formula Factories in China

“…Population structure analysis including 15 genomes in this study and an additional 108 reference genomes further revealed that the STs of C. sakazakii formed their own distinct cluster, which was in agreement with previous studies ( Lee and Andam, 2019 ; Jang et al, 2020 ). Therefore, it is essential to recognize more STs to aid in epidemiological investigations and risk assessments of this pathogen.…”

Comparative genomics reveals broad genetic diversity, extensive recombination and nascent ecological adaptation in Micrococcus luteus

“…4 b), indicating the presence of recombination. Similar decaying correlation profiles have also been shown in other recombining bacteria, such as Helicobacter pylori , Pseudomonas aeruginosa , Salmonella enterica and Cronobacter sakazakii [ 41 – 43 ]. Meanwhile, mcorr showed the mean fragment size (f̅) of a recombination event in M. luteus species was 874.45 bp; the recombination coverage (c), which indicates the proportion of sites in the genome whose diversity has come from recombination events since its last common ancestor, was 0.46; and the ratio γ/μ, the relative rate of recombination to mutation, was 10.87 (Fig.…”