Genomic analysis of clinical isolates reveals genetic diversity but little evidence of genetic determinants for diarrhoeal disease.

spp. are associated with a number of infectious syndromes in humans including gastroenteritis and dysentery. Our understanding of the genetic diversity, population structure, virulence determinants and antimicrobial resistance of the genus has been limited by a lack of sequenced genomes linked to metadata. We performed a comprehensive analysis of the whole genome sequences of 447 isolates from children in Karachi, Pakistan, with moderate-to-severe diarrhoea (MSD) and from matched controls without diarrhoea that were collected as part of the Global Enteric Multicenter Study (GEMS). Human-associated isolates exhibited high species diversity and extensive antimicrobial and virulence gene content. , , and were all significantly associated with MSD in at least one cohort group. The and genes that encode components of polar and lateral flagella, respectively, exhibited a weak association with isolates originating from cases of gastroenteritis.