title: Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia.
abstract: Infant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links. Clostridium botulinum isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS). In silico multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne bont/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of C. botulinum that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that C. botulinum from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST.
authors.affiliation: Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, NSW, Australia The Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia nadine.holmes@sydney.edu.au.
authors.forename: Nadine
authors.initials: N
authors.lastname: McCallum
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Gray
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Qinning
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ng
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Hicks
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Trang
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Marion
authors.initials: M
authors.lastname: Yuen
authors.affiliation: The Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia School of Public Health, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Hill-Cawthorne
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, NSW, Australia The Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Vitali
authors.initials: V
authors.lastname: Sintchenko
mesh_terms: D019274:Botulinum Toxins, Type A / Q000235:genetics; D001906:Botulism / Q000453:epidemiology* / Q000382:microbiology; D003014:Clostridium botulinum / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D007223:Infant; D017720:Molecular Epidemiology; D058885:Multilocus Sequence Typing; D009517:New South Wales / Q000453:epidemiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide
chemical_list: C096323:rimabotulinumtoxinB; D019274:Botulinum Toxins, Type A