Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

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chitosan oligosaccharide functionalized silver nanoparticles with synergistic bacterial activity were constructed as a multivalent inhibitor of bacteria. placing the chitosan oligosaccharide on silver nanoparticles can dramatically enhance the adsorption to the bacterial membrane via multivalent binding. the multicomponent nanostructures can cooperate synergistically against gram-positive and gram-negative bacteria. the antibacterial activity was increased via orthogonal array design to optimize the synthesis condition. The synergistic bacterial activity was confirmed by fractional inhibitory concentration and zone of inhibition test. through studies of antimicrobial action mechanism, it was found that the nanocomposites interacted with the bacteria by binding to Mg 2+ ions of the bacterial surface. then, the nanocomposites disrupted bacterial membrane by increasing the permeability of the outer membrane, resulting in leakage of cytoplasm. this strategy of chitosan oligosaccharide modification can increase the antibacterial activity of silver nanoparticles and accelerate wound healing at the same time. the nanomaterial without cytotoxicity has promising applications in bacteria-infected wound healing therapy. Human health has been threatened with abuse of antibiotics and the appearance of multiple drug-resistant bacteria 1,2. In the European Union, the number of deaths attributable to antibiotic-resistant bacteria is about 25,000 each year 3. Therefore, it is crucial to design and develop new antimicrobial materials with high antibacterial activity and low resistance in the field of biomedicine. Silver nanoparticles (AgNPs) with small size and large specific surface area have a stronger antibacterial effect against different bacteria, virus, and fungi 4-6. AgNPs can contact with bacterial cell membranes, penetrate into the cytoplasm, and then inactivate essential respiratory enzymes and proteins, leading to bacterial death 7,8. However, these antibacterial action of AgNPs is often dependent on high concentration since their physical collision with bacterial surface is random 9. For enhancing interaction of AgNPs and the bacteria, cationic polymers-stabilized AgNPs were designed to bind to the negatively charged cell surfaces of the bacteria by electrostatic interaction 10,11. However, the toxicity of cationic polymers obstructed their biomedicine application. Then, to improve their biocompatibility, collagen-stabilized AgNPs were prepared by a photochemical method 12. However, it was found that this AgNPs showed a weaker antibacterial property, comparing with small molecules-stabilized AgNPs (eg. lysine and citrate). Chitosan oligosaccharide (COS), which is a cationic, non-immunogenic, biocompatible and an FDA-recognized mucoadhesive polymer 13 , with low molecular and good water-solubility is the positively charged alkaline-amino-oligosaccharide. Several biological activities of COS, such as hemostasis, antibacterial activity and anti-inflammatory effects, have been extensively studied in biomaterials field 14. ...