Abstract
The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage–host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT104 and DT104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction–modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host–phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control.
Highlights
IntroductionNon-typhoidal Salmonella (NTS) serovars predominantly cause a self-limiting diarrhoeal illness; they have recently observed to cause invasive extra-intestinal disease, including bacteraemia and focal systemic infections [1,2]
Published: 17 April 2021Non-typhoidal Salmonella (NTS) serovars predominantly cause a self-limiting diarrhoeal illness; they have recently observed to cause invasive extra-intestinal disease, including bacteraemia and focal systemic infections [1,2].The global burden of disease caused by invasive NTS is significant and substantially exacerbated by the emergence of antibiotic resistant strains
The emergence of MDR bacteria prompted a renewal of interest in bacteriophages as clinical therapeutics and natural biocontrol agents of foodborne pathogens, including Salmonella [5]
Summary
Non-typhoidal Salmonella (NTS) serovars predominantly cause a self-limiting diarrhoeal illness; they have recently observed to cause invasive extra-intestinal disease, including bacteraemia and focal systemic infections [1,2]. The global burden of disease caused by invasive NTS is significant and substantially exacerbated by the emergence of antibiotic resistant strains. Salmonella enterica serovar Typhimurium definitive phage type DT104 and the closely related DT104b are of considerable concern worldwide [3,4]. The emergence of MDR bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents of foodborne pathogens, including Salmonella [5]. Upon injecting its genetic material into the cytoplasm of the host cell, the phage follows either a lytic or lysogenic lifecycle. The phage hijacks bacterial cell metabolic machinery
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