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Updated: Aug 15, 2025
Measuring Growth and Gene Expression Dynamics of Tumor-Targeted S. Typhimurium Bacteria
Published on: July 6, 2013
Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control
Sherif G Ahmed1, Gary J Brenner2
1Department of Anesthesiology, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, U.S.A.
Background/Aim:
This study evaluated the effect of enrofloxacin antibiotic treatment on the ability of an attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 to control schwannoma growth in a preclinical mouse schwannoma tumor model.
Materials And Methods:
The antitumor efficacy of VNP20009 intratumoral (i.t.) injection was assessed in a syngeneic mouse-NF2 schwannoma model, with and without subcutaneous (s.c.) injection of enrofloxacin beginning on day-1 or day-8 post-VNP20009 injection. S. typhimurium colonization was assessed in excised tumor samples following antibiotic treatment.
Results:
I.t. injection of the VNP20009 significantly decreased the growth of schwannoma tumors in mice compared to PBS-treated controls. Treatment of mice with enrofloxacin on day-1 post-VNP20009 injection resulted in abrogation of VNP20009-mediated tumor growth control. In contrast, tumor growth in i.t. VNP20009-injected mice infused with enrofloxacin beginning on day 8 was significantly decreased compared to i.t. PBS-injected controls. Enrofloxacin significantly reduced the number of viable VNP20009 bacteria in excised tumor samples within one day of antibiotic infusion. Viable bacteria were either few or essentially eliminated at the end of the experiment in antibiotic-treated animals compared to VNP20009-only.
Conclusion:
Viable VNP20009 can persist for as long as 2.5 weeks following intratumoral injection of schwannoma, during which time tumor growth is retarded. Antibiotic treatment starting 1-day following i.t. VNP20009 abrogated bacterial tumor growth control, whereas initiation of antibiotics 8-days following i.t. VNP20009 was associated with control of tumor growth, albeit less than seen in animals unexposed to antibiotics.
Insights
Enzyme treatment using Salmonella typhimurium VNP20009 slowed schwannoma growth in mice. However, early enrofloxacin antibiotic treatment eliminated this effect, while later treatment still showed some tumor control.
Area of Science:
- Oncology
- Microbiology
- Pharmacology
Background:
- Schwannoma is a type of tumor that grows from nerve cells.
- Attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 has shown potential in controlling tumor growth.
- The impact of antibiotic treatment on the efficacy of bacterial tumor therapy is not fully understood.
Purpose of the Study:
- To evaluate the effect of enrofloxacin antibiotic treatment on the antitumor efficacy of S. typhimurium VNP20009 in a preclinical mouse schwannoma model.
- To determine the optimal timing for enrofloxacin administration to maintain the therapeutic effect of VNP20009.
Main Methods:
- Intratumoral injection of VNP20009 was administered to mice with established schwannomas.
- Enrofloxacin was administered subcutaneously at different time points (day-1 or day-8) post-VNP20009 injection.
- Tumor growth was monitored, and S. typhimurium colonization in tumors was assessed after antibiotic treatment.
Main Results:
- Intratumoral VNP20009 injection significantly reduced schwannoma tumor growth compared to controls.
- Early enrofloxacin treatment (day-1) abrogated the VNP20009-mediated tumor growth control.
- Delayed enrofloxacin treatment (day-8) still resulted in significant tumor growth reduction, although less effective than VNP20009 alone.
- Enrofloxacin significantly reduced viable VNP20009 bacteria in tumors, with elimination observed by the end of the experiment in treated animals.
Conclusions:
- Viable VNP20009 persists in schwannoma tumors for up to 2.5 weeks, retarding tumor growth.
- Antibiotic treatment with enrofloxacin initiated one day after VNP20009 injection negates the bacterial tumor control.
- Initiating enrofloxacin treatment eight days after VNP20009 injection allows for partial tumor growth control, indicating a critical window for antibiotic intervention.
