Streptococcus pneumoniae, also known as the pneumococcus, is a major cause of life-threatening bloodstream infections, and may cross the blood-brain barrier and cause meningitis. Invasive pneumococcal disease (IPD) affects all age groups, but the populations highest at risk of infection are children, the elderly, and individuals with compromised immunity. Despite the implementation of childhood immunization programs and effective antimicrobial agents, child mortality from pneumococcal meningitis still imposes a huge disease burden, even in developed countries. This study aimed to understand the differences in patterns of Streptococcus pneumoniae genome evolution through gene loss and gain events, and their effect on the propensity to cause meningitis compared to bacteremia. Streptococcus pneumoniae isolate genomes of strains retrieved from human cerebrospinal fluid (CSF) were compared to those retrieved from human peripheral blood. The two datasets were first each analyzed separately, followed by comparisons across the two subsets. Briefly, the sequences in each data subset were first broadly compared using an All vs All BLAST comparison. The BLAST results were then more accurately clustered into orthologous groups using a hidden Markov chain model algorithm called OrthoMCL. The resultant orthologous map generated was then annotated and processed using Bacterial Makeup eXplorer (BMX) to generate annotated phyletic patterns highlighting gene presence and absence. The phyletic patterns were further analyzed using the Gene Loss Mapping Engine (GLOOME) to determine the probability of genes acquisition or loss along the length of each genome in the dataset under study. The results were then analyzed to make inference of the general direction of evolution, which is gene gain or loss events, which are associated with propensity to cause meningitis or not; when comparing the meningitis and bacteremia associated data subsets. Among the known virulence proteins, putative bacteriocin transporter C39 protease domain BlpA2 and pneumococcal histidine triad protein D (bvh-11-2) showed more gene loss events in the meningitis set. The immunity protein PncB, pncF, immunity protein PncK and bacteriocin BlpO displayed more gene loss events in the bacteremia set. More gene loss events were observed in both bacteremia and meningitis sets for putative immunity protein PncM and putative membrane protein BlpL. Also, more gene gain in both sets was observed for putative uncharacterized protein PncC. There was more gene gain in bacteremia set for cell surface choline binding protein PcpA. The overall findings suggests that meningitis genomes were more conserved compared to those generated from bacteremia isolates. They highlight mechanisms that determine differences in invasive ability during infection since gene loss and acquisition primarily contribute to how bacteria genetically adapt to novel environments and diverge to form separate, evolutionarily distinct species and strains. Genetic flux can radically and rapidly increase fitness or alter some aspects of lifestyle, such as multidrug non-susceptibility.

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