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Characterisation of Phage Susceptibility Variation in Salmonellaenterica Serovar Typhimurium DT104 and DT104b
Manal Mohammed1, Beata Orzechowska1
1School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, Fitzrovia, London W1W 6XH, UK.
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.
Insights
Multidrug-resistant bacteria drive renewed interest in bacteriophages (phages). Whole genome sequencing revealed no genetic differences explaining phage resistance variations between Salmonella Typhimurium DT104 and DT104b strains.
Area of Science:
- Microbiology
- Genomics
- Bacteriophage Therapy
Background:
- Multidrug-resistant (MDR) bacteria pose a significant global health threat, increasing mortality and morbidity.
- Bacteriophages (phages), viruses that infect bacteria, are being re-evaluated as therapeutic agents and biocontrol agents.
- The evolutionary arms race between bacteria and phages involves co-evolving resistance mechanisms, leading to complex host-phage interactions.
Purpose of the Study:
- To investigate the genomic basis for differential phage susceptibility between Salmonella Typhimurium DT104 and DT104b, two epidemiologically related phage types.
- To characterize phage resistance mechanisms and genomic variations contributing to distinct phage reaction patterns.
Main Methods:
- Whole genome sequencing (WGS) was employed to analyze the genomes of S. Typhimurium DT104 and DT104b.
- Analysis included intact prophages, restriction-modification systems (RMS), plasmids, and clustered regularly interspaced short palindromic repeats (CRISPRs) and associated proteins.
- Genes encoding potential phage receptors were also examined.
Main Results:
- No unique genetic determinants were identified that explain the observed differences in phage susceptibility between DT104 and DT104b.
- Analysis of genes for potential phage receptors showed no significant differences between the two strains.
- The study did not find genomic variations in prophages, RMS, plasmids, or CRISPR-Cas systems that account for the divergent phage profiles.
Conclusions:
- The observed variations in phage susceptibility between S. Typhimurium DT104 and DT104b are not explained by the analyzed genomic features.
- Further experimental studies, including assessment of phage-specific receptors and transcriptomic analysis (RNA sequencing), are needed to elucidate these differences.
- Understanding these host-phage interactions is crucial for advancing phage-based technologies for effective infection control.
