Vibrio cholerae 01 A-Bvaccine strain JBK 70 and A-B' CVD 101 prepared by recombinant DNA techniques from pathogenic El Tor Inaba N16961 and classical Ogawa 395, respectively, were fed to 38 volunteers in single doses of 104 to 1010. Although severe diarrhea did not occur in any vaccinee, more than one-hplf developed mild diarrhea. These attenuated strains colonized well and elicited prominent vibriocidal and antitoxic (CVD 101) antibody responses. Recipients of a single dose of JBK 70 were significantly protected when challenged with 106 wild-type N16961. Diarrhea occurred in 7 of 8 controls but in only 1 of 10 vaccinees (P < 0.003, 89% vaccine efficacy), demonstrating the potency of immune mechanisms that do not involve cholera antitoxin. Further derivatives were prepared to explore the pathogenesis of the residual diarrhea, considering that either intestinal colonization by the vaccine itself or accessory toxins might be responsible. CVD 102, an auxotrophic mutant of CVD 101, did not cause diarrhea but colonized poorly and elicited feeble immune responses. Derivatives of JBK 70 and CVD 101 (CVD 104 and 105) deleted of genes encoding the El Tor hemolysin still caused mild diarrhea. Genetically engineered strains can be colonizing, highly immunogenic, and protective single-dose oral vaccines, but they must be further attenuated before they can be considered for use as public health tools.

Objectives: The aim of this study was to characterize a collection of 520 Salmonella enterica serovar Infantis strains isolated from food (poultry meat), human infections and environmental sources from the years 2010, 2013 and 2015 in Switzerland.Methods: We performed antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) analysis on all 520 S. Infantis isolates, and whole genome sequencing (WGS) on 32 selected isolates.Results: The majority (74.8%) of the isolates was multidrug resistant (MDR). PFGE analysis revealed that 270 (51.9%) isolates shared an identity of 90%. All isolates subjected to WGS belonged to sequence type (ST) 32 or a double-locus variant thereof (one isolate). Seven (21.9%) of the sequenced isolates were phylogenetically related to the broiler-associated clone B that emerged in Hungary and subsequently spread within and outside of Europe. In addition, three isolates harboring blaCTX-M-65 on a predicted large (∼320 kb) plasmid grouped in a distinct cluster.Conclusion: This study documents the presence of the Hungarian clone B and related clones in food and human isolates between 2010 and 2015, and the emergence of a blaCTX-M-65 harboring MDR S. serovar Infantis lineage.

Two Salmonella typhi mutants, 541Ty (Vi+) and 543Ty (Vi-)

Multilocus enzyme electrophoresis was employed to measure chromosomal genotypic diversity and evolutionary relationships among 761 isolates of the serovars Salmonella typhi, S. paratyphi A, S. paratyphi B, S. paratyphi C, and S. sendai, which are human-adapted agents of enteric fever, and S. miami and S. java, which are serotypically similar to S. sendai and S. paratyphi B, respectively, but cause gastroenteritis in both humans and animals. To determine the phylogenetic positions of the clones of these forms within the context of the salmonellae of subspecies I, comparative data for 22 other common serovars were utilized. Except for S. paratyphi A and S. sendai, the analysis revealed no close phylogenetic relationships among clones of different human-adapted serovars, which implies convergence in host adaptation and virulence factors. Clones of S. miami are not allied with those of S. sendai or S. paratyphi A, being, instead, closely related to strains of S. panama. Clones of S. paratyphi B and S. java belong to a large phylogenetic complex that includes clones of S. typhimurium, S. heidelberg, S. saintpaul, and S. muenchen. Most strains of S. paratyphi B belong to a globally distributed clone that is highly polymorphic in biotype, bacteriophage type, and several other characters, whereas strains of S. java represent seven diverse lineages. The flagellar monophasic forms of S. java are genotypically more similar to clones of S. typhimurium than to other clones of S. java or S. paratyphi B. Clones of S. paratyphi C are related to those of S. choleraesuis. DNA probing with a segment of the viaB region specific for the Vi capsular antigen genes indicated that the frequent failure of isolates of S. paratyphi C to express Vi antigen is almost entirely attributable to regulatory processes rather than to an absence of the structural determinant genes themselves. Two clones of S. typhisuis are related to those of S. choleraesuis and S. paratyphi C, but a third clone is not. Although the clones of S. decatur and S. choleraesuis are serologically and biochemically similar, they are genotypically very distinct. Two clones of S. typhi were distinguished, one globally distributed and another apparently confined to Africa; both clones are distantly related to those of all other serovars studied.