Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants



Paulson, Joseph N, Williams, Brent L, Hehnly, Christine, Mishra, Nischay, Sinnar, Shamim A, Zhang, Lijun, Ssentongo, Paddy, Mbabazi-Kabachelor, Edith, Wijetunge, Dona SS, von Bredow, Benjamin
et al (show 42 more authors) (2020) Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. SCIENCE TRANSLATIONAL MEDICINE, 12 (563).

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Abstract

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.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 15 Jan 2021 09:58
Last Modified: 08 Oct 2021 02:11
DOI: 10.1126/scitranslmed.aba0565
Open Access URL: https://www.medrxiv.org/content/10.1101/2020.08.03...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3104136