Tumour microbiomes and Fusobacterium genomics in Vietnamese colorectal cancer patients.

Perturbations in the gut microbiome have been associated with colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite its significance in the promotion of CRC, genomic studies of Fusobacterium is limited. We enrolled 43 Vietnamese CRC patients and 25 participants with non-cancerous colorectal polyps to study the colonic microbiomes and genomic diversity of Fusobacterium in this population, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome analysis. Oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour microbiomes. We obtained 53 Fusobacterium genomes, representing 26 strains, from the saliva, tumour and non-tumour tissues of six CRC patients. Isolates from the gut belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of Fusobacterium periodonticum. The Fusobacterium population within each individual was distinct and in some cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within four individuals, tumour-associated Fusobacterium were clonal to those isolated from non-tumour tissues. Genes encoding major virulence factors (Fap2 and RadD) showed evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.

Exploring the Genomic Diversity and Antimicrobial Susceptibility of Bifidobacterium pseudocatenulatum in a Vietnamese Population.

Bifidobacterium pseudocatenulatum is a member of the human gut microbiota, and specific variants of B. pseudocatenulatum have been associated with health benefits such as improving gut integrity and reducing inflammatory responses. Here, we aimed to assess the genomic diversity and predicted metabolic profiles of B. pseudocatenulatum cells found colonizing the gut of healthy Vietnamese adults and children. We found that the population of B. pseudocatenulatum from each individual was distinct and highly diverse, with intraclonal variation attributed largely to a gain or loss of carbohydrate-utilizing enzymes. The B. pseudocatenulatum genomes were enriched with glycosyl hydrolases predicted to target plant-based nondigestible carbohydrates (GH13, GH43) but not host-derived glycans. Notably, the exopolysaccharide biosynthesis region from organisms isolated from healthy children showed extensive genetic diversity and was subject to a high degree of genetic modification. Antimicrobial susceptibility profiling revealed that the Vietnamese B. pseudocatenulatum cells were uniformly susceptible to beta-lactams but exhibited variable resistance to azithromycin, tetracycline, ciprofloxacin, and metronidazole. The genomic presence of ermX and tet variants conferred resistance against azithromycin and tetracycline, respectively; ciprofloxacin resistance was associated with a mutation(s) in the quinolone resistance-determining region (GyrA, S115, and/or D119). Our work provides the first detailed genomic and antimicrobial resistance characterization of B. pseudocatenulatum found in the Vietnamese population, which can be exploited for the rational design of probiotics. IMPORTANCE Bifidobacterium pseudocatenulatum is a beneficial member of the human gut microbiota. The organism can modulate inflammation and has probiotic potential, but its characteristics are largely strain dependent and associated with distinct genomic and biochemical features. Population-specific beneficial microbes represent a promising avenue for the development of potential probiotics, as they may exhibit a more suitable profile in the target population. This study investigates the underexplored diversity of B. pseudocatenulatum in Vietnam and provides more understanding of its genomic diversity, metabolic potential, and antimicrobial susceptibility. Such data from indigenous populations are essential for selecting probiotic candidates that can be accelerated into further preclinical and clinical investigations.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

OBJECTIVES: The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. METHODS: IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. RESULTS: IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. CONCLUSIONS: We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.