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

Joseph N. Paulson, Brent L. Williams, Christine Hehnly, Nischay Mishra, Shamim A. Sinnar, Lijun Zhang, Paddy Ssentongo, Edith Mbabazi-Kabachelor, Dona S.S. Wijetunge, Benjamin Von Bredow, Ronnie Mulondo, Julius Kiwanuka, Francis Bajunirwe, Joel Bazira, Lisa M. Bebell, Kathy Burgoine, Mara Couto-Rodriguez, Jessica E. Ericson, Tim Erickson, Matthew FerrariMelissa Gladstone, Cheng Guo, Murali Haran, Mady Hornig, Albert M. Isaacs, Brian Nsubuga Kaaya, Sheila M. Kangere, Abhaya V. Kulkarni, Elias Kumbakumba, Xiaoxiao Li, David D. Limbrick, Joshua Magombe, Sarah U. Morton, John Mugamba, James Ng, Peter Olupot-Olupot, Justin Onen, Mallory R. Peterson, Farrah Roy, Kathryn Sheldon, Reid Townsend, Andrew D. Weeks, Andrew J. Whalen, John Quackenbush, Peter Ssenyonga, Michael Y. Galperin, Mathieu Almeida, Hannah Atkins, Benjamin C. Warf, W. Ian Lipkin, James R. Broach, Steven J. Schiff

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article numbereaba0565
JournalScience translational medicine
Volume12
Issue number563
DOIs
StatePublished - Sep 30 2020

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