Dataset Information

Complete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156.

ABSTRACT: We have isolated a likely bacterial pathogen from cerebrospinal fluid from a Ugandan infant suffering from hydrocephalus. Whole-genome sequencing and assembly of the genome of the clinical isolate, as well as that of a previously deposited reference strain, identified the isolate as Paenibacillus thiaminolyticus, which has not been associated with widespread human infections.

SUBMITTER: Hehnly C

PROVIDER: S-EPMC7380522 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Complete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156.

Hehnly Christine C Zhang Lijun L Paulson Joseph N JN Almeida Mathieu M von Bredow Benjamin B Wijetunge Dona S S DSS Galperin Michael Y MY Sheldon Kathryn K Schiff Steven J SJ Broach James R JR

Microbiology resource announcements 20200409 15

We have isolated a likely bacterial pathogen from cerebrospinal fluid from a Ugandan infant suffering from hydrocephalus. Whole-genome sequencing and assembly of the genome of the clinical isolate, as well as that of a previously deposited reference strain, identified the isolate as <i>Paenibacillus thiaminolyticus</i>, which has not been associated with widespread human infections. ...[more]

PMID: 32273361

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Project description:Hydrocephalus, the leading indication for childhood neurosurgery worldwide, is particularly prevalent in low- and middle-income countries. Hydrocephalus preceded by an infection, or postinfectious hydrocephalus, accounts for up to 60% of hydrocephalus in these areas. Since many children with hydrocephalus suffer poor long-term outcomes despite surgical intervention, prevention of hydrocephalus remains paramount. Our previous studies implicated a novel bacterial pathogen, Paenibacillus thiaminolyticus, as a causal agent of neonatal sepsis and postinfectious hydrocephalus in Uganda. Here, we report the isolation of three P. thiaminolyticus strains, Mbale, Mbale2, and Mbale3, from patients with postinfectious hydrocephalus. We constructed complete genome assemblies of the clinical isolates as well as the nonpathogenic P. thiaminolyticus reference strain and performed comparative genomic and proteomic analyses to identify potential virulence factors. All three isolates carry a unique beta-lactamase gene, and two of the three isolates exhibit resistance in culture to the beta-lactam antibiotics penicillin and ampicillin. In addition, a cluster of genes carried on a mobile genetic element that encodes a putative type IV pilus operon is present in all three clinical isolates but absent in the reference strain. CRISPR-mediated deletion of the gene cluster substantially reduced the virulence of the Mbale strain in mice. Comparative proteogenomic analysis identified various additional potential virulence factors likely acquired on mobile genetic elements in the virulent strains. These results provide insight into the emergence of virulence in P. thiaminolyticus and suggest avenues for the diagnosis and treatment of this novel bacterial pathogen. IMPORTANCE Postinfectious hydrocephalus, a devastating sequela of neonatal infection, is associated with increased childhood mortality and morbidity. A novel bacterial pathogen, Paenibacillus thiaminolyticus, is highly associated with postinfectious hydrocephalus in an African cohort. Whole-genome sequencing, RNA sequencing, and proteomics of clinical isolates and a reference strain in combination with CRISPR editing identified type IV pili as a critical virulence factor for P. thiaminolyticus infection. Acquisition of a type IV pilus-encoding mobile genetic element critically contributed to converting a nonpathogenic strain of P. thiaminolyticus into a pathogen capable of causing devastating diseases. Given the widespread presence of type IV pilus in pathogens, the presence of the type IV pilus operon could serve as a diagnostic and therapeutic target in P. thiaminolyticus and related bacteria.

Dataset Information

Complete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156.

Publications

Complete Genome Sequences of the Human Pathogen Paenibacillus thiaminolyticus Mbale and Type Strain P. thiaminolyticus NRRL B-4156.

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