Prediction of Prophages and Their Host Ranges in Pathogenic and Commensal Neisseria Species

The genus includes two pathogenic species, N. gonorrhoeae and N. meningitidis, and numerous commensal species. species frequently exchange DNA with one another, primarily via transformation and homologous recombination and via multiple types of mobile genetic elements (MGEs). Few bacteriophages (phages) have been identified, and their impact on bacterial physiology is poorly understood. Furthermore, little is known about the range of species that phages can infect. In this study, we used three virus prediction tools to scan 248 genomes of 21 different species and identified 1,302 unique predicted prophages. Using comparative genomics, we found that many predictions are dissimilar from prophages and other MGEs previously described to infect species. We also identified similar predicted prophages in genomes of different species. Additionally, we examined CRISPR-Cas targeting of each genome and predicted prophage. While CRISPR targeting of chromosomal DNA appears to be common among several species, we found that 20% of the prophages we predicted are targeted significantly more than the rest of the bacterial genome in which they were identified (i.e., backbone). Furthermore, many predicted prophages are targeted by CRISPR spacers encoded by other species. We then used these results to infer additional host species of known prophages and predictions that are highly targeted relative to the backbone. Together, our results suggest that we have identified novel prophages, several of which may infect multiple species. These findings have important implications for understanding horizontal gene transfer between members of this genus. Drug-resistant Neisseria gonorrhoeae is a major threat to human health. Commensal species are thought to serve as reservoirs of antibiotic resistance and virulence genes for the pathogenic species N. gonorrhoeae and N. meningitidis. Therefore, it is important to understand both the diversity of mobile genetic elements (MGEs) that can mediate horizontal gene transfer within this genus and the breadth of species these MGEs can infect. In particular, few bacteriophages (phages) are known to infect species. In this study, we identified a large number of candidate phages integrated in the genomes of commensal and pathogenic species, many of which appear to be novel phages. Importantly, we discovered extensive interspecies targeting of predicted phages by CRISPR-Cas systems, which may reflect their movement between different species. Uncoveri