Diverse Prophage Elements of Salmonella enterica Serovars Show Potential Roles in Bacterial Pathogenicity.

Nontyphoidal salmonellosis is an important foodborne and zoonotic infection that causes significant global public health concern. Diverse serovars are multidrug-resistant and encode several virulence indicators; however, little is known on the role prophages play in driving these traits. Here, we extracted prophages from seventy-five Salmonella genomes which represent the fifteen important serovars in the United Kingdom. We analyzed the intact prophages for the presence of virulence genes and established their genomic relationships. We identified 615 prophages from the Salmonella strains, from which 195 prophages are intact, 332 are incomplete, while 88 are questionable. The average prophage carriage was found to be 'extreme' in S. Heidelberg, S. Inverness, and S. Newport (10.2-11.6 prophages/strain), 'high' in S. Infantis, S. Stanley, S. Typhimurium, and S. Virchow (8.2-9.0 prophages/strain), 'moderate' in S. Agona, S. Braenderup, S. Bovismorbificans, S. Choleraesuis, S. Dublin, and S. Java (6.0-7.8 prophages/strain), and 'low' in S. Javiana and S. Enteritidis (5.8 prophages/strain). Cumulatively, 61 virulence genes (1500 gene copies) were detected from representative intact prophages and linked to Salmonella delivery/secretion system (42.62%), adherence (32.7%), magnesium uptake (3.88%), regulation (5%), stress/survival (1.6%), toxins (10%), and antivirulence (1.6%). Diverse clusters were formed among the intact prophages and with bacteriophages of other enterobacteria, suggesting different lineages and associations. Our work provides a strong body of data to support the contributions diverse prophages make to the pathogenicity of Salmonella, including thirteen previously unexplored serovars.

Novel Escherichia coli-Infecting Bacteriophages Isolated from Uganda That Target Human Clinical Isolates.

Background: The antimicrobial resistance catastrophe is a growing global health threat and predicted to be worse in developing countries. Phages for Global Health (PGH) is training scientists in these regions to isolate relevant therapeutic phages for pathogenic bacteria within their locality, and thus contributing to making phage technology universally available. Materials and Methods: During the inaugural PGH workshop in East Africa, samples from Ugandan municipal sewage facilities were collected and two novel Escherichia coli lytic phages were isolated and characterized. Results: The phages, UP19 (capsid diameter ∼100 nm, contractile tail ∼120/20 nm) and UP30 (capsid diameter ∼70 nm, noncontractile tail of ∼170/20 nm), lysed ∼82% and ∼36% of the 11 clinical isolates examined, respectively. The genomes of UP19 (171.402 kb, 282 CDS) and UP30 (49.834 kb, 75 CDS) closely match the genera Dhakavirus and Tunavirus, respectively. Conclusion: The phages isolated have therapeutic potential for further development against E. coli infections.

Unravelling the Links between Phage Adsorption and Successful Infection in Clostridium difficile.

Bacteriophage (phage) therapy is a promising alternative to antibiotics for the treatment of bacterial pathogens, including Clostridiumdifficile. However, as for many species, in C. difficile the physical interactions between phages and bacterial cells have not been studied in detail. The initial interaction, known as phage adsorption, is initiated by the reversible attachment of phage tail fibers to bacterial cell surface receptors followed by an irreversible binding step. Therefore binding can dictate which strains are infected by the phage. In this study, we investigated the adsorption rates and irreversible binding of three C. difficile myoviruses: CDHM1, CDHM3 and CDHM6 to ten strains that represent ten prevalent C. difficile ribotypes, regardless of their ability to infect. CDHM1 and CDHM3 phage particles adsorbed by ~75% to some strains that they infected. The infection dynamics for CDHM6 are less clear and ~30% of the phage particles bound to all strains, irrespective of whether a successful infection was established. The data highlighted adsorption is phage-host specific. However, it was consistently observed that irreversible binding had to be above 80% for successful infection, which was also noted for another two C. difficile myoviruses. Furthermore, to understand if there is a relationship between infection, adsorption and phage tail fibers, the putative tail fiber protein sequences of CDHM1, CDHM3 and CDHM6 were compared. The putative tail fiber protein sequence of CDHM1 shares 45% homology at the amino acid level to CDHM3 and CDHM6, which are identical to each other. However, CDHM3 and CDHM6 display differences in adsorption, which highlights that there is no obvious relationship between putative tail fiber sequence and adsorption. The importance of adsorption and binding to successful infection is often overlooked, and this study provides useful insights into host-pathogen interactions within this phage-pathogen system.