Virulent Bacteriophages for Controlling Shiga Toxin–Producing Escherichia coli Without Inducing Toxin Production

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Abstract
Shiga toxin–producing Escherichia coli (STEC) infections pose a significant public health challenge, characterized by severe complications including hemolytic uremic syndrome (HUS) due to Shiga toxin (Stx) production. Current therapeutic approaches encounter a critical limitation, as conventional antibiotic treatment is contraindicated due to its propensity to trigger bacterial SOS response and subsequently enhance Stx production, which increases the likelihood of developing HUS in antibiotic-treated patients. The lack of effective, safe therapeutic options has created an urgent need for alternative treatment strategies for STEC infections. This study investigates the therapeutic potential of virulent bacteriophages (phages) against STEC O157:H7. Our findings demonstrate that these phages effectively reduce STEC populations to levels comparable to ciprofloxacin treatment, while crucially avoiding the induction of SOS response and subsequent enhancement of Stx production. This is a significant advantage over conventional antibiotics, which increase Stx levels. Furthermore, these phages exhibited broad-spectrum antimicrobial activity against multiple clinical STEC isolates without triggering toxin expression. The capability of virulent phages to effectively control STEC without enhancing toxin production represents a promising therapeutic strategy that combines antimicrobial efficacy with safety considerations. These characteristics indicate that virulent phages represent a potential solution to address the current therapeutic challenges in STEC infections, particularly in mitigating the risk of HUS development in infected patients.

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