Abstract Background Neonatal meningitis is a public health challenge for pediatricians. Neonatal meningitis Escherichia coli (NMEC) is the most common Gram-negative bacterial cause of sepsis and meningitis in newborns in the United States. NMEC strains can replicate in macrophages, survive in the bloodstream and traverse the blood-brain barrier, resulting in meningitis. Most NMEC cases are associated with serogroups O18, O83, O7, O12, O1, and O45 (Logue et al., 2012). Two clusters of the Type 6 Secretion System (T6SS-I and T6SS-II) were identified in an NMEC O18:K1 strain, and studies have demonstrated that T6SS plays an essential role in the pathogenesis of several bacterial species. However, there is still a lack of knowledge regarding the function of some T6SS genes. Here, we investigated the role of T6SS in different NMEC serogroups to identify specific genes that may be used as a potential target for an efficacious prevention strategy. Characteristics of NMEC strainsFigure 1.Characteristics of NMEC strains used in this study. A) Percentage of serogroups; B) Prevalence of T6SS among the NMEC isolates. Methods A total of 120 NMEC genomes were used in this study (n=78 from the Logue Lab collection; n=42 publicly databases). The T6SS clusters were identified through BLAST analysis using NMEC RS218 and O18 as reference genomes. To establish the presence of a specific cluster, a query cover and percentage identity threshold of 60% and 70% were set. The sequence comparisons were performed using the Artemis Comparison Tool (ACT). Results The serogroup O18 was the most abundant (23%; n=28), followed by O1 (22%; n=26), and O83 (12%; n=14). Analysis examined the prevalence of both T6SS clusters in the NMEC genomes and identified that they were present in 69% (n=83) of the genomes, while 12% (n=14) have only one of the clusters, and 19% (n=23) have no clusters. The presence of both T6SS clusters was observed in the serogroups O18, O14, and O2/O50. In contrast, no gene of any cluster was identified in serogroup O7. To understand the role of variation among the serogroups, in vitro analyses were performed. The results indicate differences in survival within THP-1 macrophages-like among distinct serogroups. Conclusion Our results support the hypothesis that T6SS components differ among the NMEC serogroups, potentially impacting their pathogenicity and ability to cause meningitis. These findings have significant implications for development of a prevention strategy for neonatal meningitis. Disclosures All Authors: No reported disclosures
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