Differential Multiplicities of Infection and the Transcriptional Response of Salmonella Enterica to Bacteriophage Treatments

Michael Smith^*
*Correspondence: Michael Smith, Department of Pharmacogenomics, University of Amsterdam, 1012 WX Amsterdam, Netherlands, Email:

Introduction

Salmonella Enterica is a pathogenic bacterium that poses significant threats to public health globally. It is a leading cause of foodborne illnesses, with infections ranging from mild gastroenteritis to severe systemic diseases. The emergence of antibiotic-resistant strains of Salmonella has further complicated the treatment of infections, highlighting the need for alternative therapeutic strategies. Bacteriophages, viruses that infect and kill bacteria, have garnered attention as potential biocontrol agents against bacterial pathogens like Salmonella. Understanding the dynamics of bacteriophage infection, particularly the concept of differential Multiplicities Of Infection (MOIs), and their impact on the transcriptional response of S. Enterica, is crucial for developing effective phage-based therapies [1].

Differential multiplicities of infection refer to the varying ratios of phages to bacterial cells in a population during infection. This phenomenon plays a significant role in determining the outcome of phage therapy, influencing factors such as phage replication, bacterial resistance mechanisms, and overall treatment efficacy. Additionally, the transcriptional response of Salmonella to bacteriophage treatments provides insights into how the bacterium adapts and responds to phage-induced stress. By elucidating these molecular mechanisms, researchers can optimize phage therapy protocols and overcome challenges such as phage resistance and treatment failure [2].

Description

The success of bacteriophage therapy relies on understanding the complex dynamics of phage-bacterium interactions. At different MOIs, distinct outcomes can occur, ranging from successful bacterial eradication to the emergence of phage-resistant mutants. Low MOIs typically favor lysogenic pathways, where phages integrate their genomes into bacterial chromosomes, potentially providing fitness advantages to the host bacteria. In contrast, high MOIs often result in lytic infections, leading to rapid bacterial lysis and phage replication. The concept of differential MOIs encompasses both the quantitative aspect (phage-to-bacterium ratio) and the qualitative aspect (phage adsorption, replication, and host range). Studies have shown that the initial MOI influences phage population dynamics within bacterial populations. For instance, a low initial MOI may lead to longer latency periods as phages undergo a slower buildup before triggering widespread lysis, whereas a high initial MOI can cause rapid bacterial killing but may also select for phageresistant mutants [3].

Upon encountering bacteriophages, bacteria undergo extensive transcriptional reprogramming to mount defense mechanisms or adapt to phage-induced stress. Transcriptional profiling, through techniques like RNA sequencing (RNA-seq), has provided valuable insights into the gene expression changes in S. Enterica following phage exposure. One of the key responses observed is the upregulation of genes associated with phage resistance mechanisms, such as CRISPR-Cas systems, restriction-modification systems, and abortive infection systems. These systems act as barriers against phage infection by either degrading foreign nucleic acids or inducing cell death to prevent phage propagation. Conversely, phage-sensitive strains may exhibit downregulation of these defense genes, making them more susceptible to phage predation [4].

The findings from studies on the transcriptional response of Salmonella to bacteriophage treatments have significant implications for the development of phage-based therapies. By targeting specific genes or pathways involved in phage resistance, researchers can design phage cocktails or genetically engineered phages to overcome bacterial defenses and enhance treatment efficacy. For example, combining phages that target different bacterial receptors or utilizing CRISPR-Cas inhibitors can prevent the emergence of phage-resistant mutants. Additionally, understanding how phages influence virulence gene expression can lead to the development of phage-mediated virulence control strategies. By selecting phages that downregulate key virulence factors, such as those involved in biofilm formation or toxin production, it may be possible to attenuate Salmonella pathogenicity without relying solely on antibiotic treatment [5].

Conclusion

In conclusion, the differential multiplicities of infection and the transcriptional response of S. Enterica to bacteriophage treatments are critical areas of research that hold promise for combating Salmonella infections. By understanding how varying MOIs influence phage-bacterium interactions and deciphering the molecular mechanisms underlying bacterial responses to phage predation, researchers can optimize phage therapy strategies for enhanced efficacy and reduced resistance development.

Moving forward, interdisciplinary collaborations between microbiologists, geneticists, bioinformaticians, and clinicians will be essential for translating these findings into clinically relevant interventions. With continued advancements in phage isolation, characterization, and delivery methods, phage therapy has the potential to revolutionize the treatment of Salmonella infections and contribute to the broader efforts in combating antibiotic-resistant bacteria.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Wang, Yaqi, Jiangtao Wu, Mengxin Lv and Zhen Shao, et al. "Metabolism characteristics of lactic acid bacteria and the expanding applications in food industry." Front Bioengineer Biotechnol 9 (2021): 612285.

   Google Scholar, Crossref, Indexed at

2. Moye, Zachary D., Joelle Woolston and Alexander Sulakvelidze. "Bacteriophage applications for food production and processing." Viruses 10 (2018): 205.

   Google Scholar, Crossref, Indexed at

3. Padhi, Bhaja K., Manjeet Singh, Marianela Rosales and Guillaume Pelletier, et al. "A PCR-based quantitative assay for the evaluation of mRNA integrity in rat samples." Biomol Detect Quantific 15 (2018): 18-23.

   Google Scholar, Crossref, Indexed at

4. Fleige, Simone and Michael W. Pfaffl. "RNA integrity and the effect on the real-time qRT-PCR performance." Mol Aspects Med 27 (2006): 126-139.

   Google Scholar, Crossref, Indexed at

5. Guiney, Donald G. and Joshua Fierer. "The role of the spv genes in Salmonella pathogenesis." Front Microbiol 2 (2011): 129.

   Google Scholar, Crossref, Indexed at