Antibiotic Resistance Networks for Phage-Antibiotic Combinatorial Metastable Host-Phage-Pathogen Triads in Meat Microbiomes: Decoding Epistatic Design"

Abstract

Salmonella infections remain a significant global public health issue, and both developed and developing countries are financially impacted by the costs of illness prevention, treatment, and surveillance. Gastroenteritis is the most common symptom of a Salmonella infection worldwide, followed by bacteremia and enteric fever. Unsanitary conditions, partly cooked vegetables, and tainted water are the main ways that Salmonella spreads. Salmonellosis affects both humans and animals equally. The emergence of antibiotic-resistant meat-borne pathogens poses a significant threat to food safety and public health, necessitating innovative biocontrol strategies. This study employs a systems microbiology approach to investigate the dynamic interactions between bacteriophages and meat-associated bacterial pathogens, focusing on their evolutionary arms race, antibiotic resistance modulation, and potential for precision biocontrol. Through multi-omics analyses (metagenomics, transcriptomics, and proteomics), we characterize phage-host coevolution in meat ecosystems, identifying genetic determinants of resistance and susceptibility.  Additionally, we explore how phage predation influences bacterial resistome and assess the feasibility of phage-based interventions to mitigate pathogen persistence. Our findings highlight the potential of tailored phage cocktails as sustainable alternatives to antibiotics in meat processing, while addressing challenges such as bacterial escape mechanisms and phage stability in food matrices. This research bridges fundamental microbial ecology with applied food safety, offering novel insights into phage-augmented pathogen control in the meat industry.

Keywords: Phage-Antibiotic Synergy, Bacteriophage Therapy, Combinatorial Antimicrobials, Multidrug-Resistant Bacteria, Livestock-Associated Resistance, Phage Predation, Metagenomic Surveillance.