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@#Introduction: Bacteria had long been known to have tumour-targeting and tumour inhibition capabilities and have re-emerged into the limelight of cancer research as a possible alternative treatment for solid tumours. Conventional therapies for solid tumours are either by surgery, chemotherapy, radiotherapy, which are very invasive and non-specific to the tumours and results in various adverse effects on the patients. Bacterial Mediated Tumour Therapy often utilises attenuated bacteria as therapeutic agents to ensure reduced pathogenicity of the strains. However, this often results in lower invasiveness towards the tumours itself. In this study, we studied the tumour inhibition capabilities of Salmonella Pathogenicity Island (SPI) attenuated Salmonella Typhimurium (S. Typhimurium) and Salmonella Agona (S. Agona), specifically with attenuation of sopB, sopD, and pipD genes. Methods: Balb/c mice bearing CT26 tumours were inoculated with S. Typhimurium and S. Agona, both unattenuated and ΔsopBΔsopDΔpipD attenuated strains. Tumour volumes were monitored daily. Organs and blood were collected for plasma liver enzyme analysis and histopathology studies on testis, liver, kidneys and brain. Results: The ΔsopBΔsopDΔpipD S. Agona treated group showed improved inhibition of tumour growth with 51.11% tumour volume reduction compared to unattenuated S. Agona. The ΔsopBΔsopDΔpipD strains have also shown lesser systemic effects as observed in plasma and histopathological studies) compared to its unattenuated counterparts. Conclusion: The present study showed that ΔsopBΔsopDΔpipD S. Agona has a great potential to be utilised as tumour therapeutic agent as it exerts lesser systemic effect while having similar tumour inhibition capabilities as the well-studied S. Typhimurium strain.
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Se evaluaron retrospectivamente las características clínicas de 59 pacientes con aislamientos extraintestinales de Salmonella enterica no Typhi y la resistencia antibiótica entre 1988 y 2004. En el 95% de los casos se conocieron las condiciones de base del huésped que consistieron en: enfermedad oncohematológica (15), lupus eritematoso sistémico (11), síndrome de inmuno deficiencia adquirida (10), pacientes internados en neonatología (8), colecistitis (4) y otras (7). Las formas clínicas halladas fueron: bacteriemias primarias (26), bacteriemias secundarias a gastroenteritis (15), artritis séptica (7), infección urinaria (12), infección intraabdominal (5), meningitis (1) y pericarditis (1). En 29 pacientes se aisló Salmonella enterica no Typhi en más de una localización. El 15,8% y el 21,0% de 59 aislamientos presentaron resistencia a cefalosporinas de 3ª generación y a ampicilina, respectivamente. Salmonella Agona causó un brote epidémico en la sala de cuidados intensivos de neonatología, aislándose de sangre en 5 pacientes y en uno también de LCR. Este serotipo fue multirresistente. Imipenem, trimetroprima-sulfometoxazol y ciprofloxacina fueron los antibióticos más activos (CIM 50: 0,5; 0,5 y 0,002 µg/mL, respectivamente).
The clinical and antimicrobial resistance of 59 patients with extraintestinal infection by nontyphi Salmonella was retrospectively evaluated from 1988 to 2004. In 95% of the patients there were underlying diseases, which included: oncohematologic disease (15), systemic lupus erythematosus (11), acquired immunodeficiency disease (AIDS) (10), patients of neonatal units (8), colecistitis (4), and other disorders (7). The clinical manifestation were primary bacteremias (26), bacteremias secondary to gastroenteritis (15), arthritis (7), urinary tract infections (12), abdominal infections (5), meningitis (1) and pericarditis (1). In 29 patients Salmonella enterica no Typhi was isolated in more than one site. Resistance to third generation cephalosporins was observed in 15,8 % of these isolates, and resistance to ampicillin in 21,0%. Salmonella Agona was isolated from an outbreak in neonatal ICU; the organism was recovered from blood samples of five neonates and in one patient also isolated from CSF. These isolates showed multiresistance. Imipenem, trimetoprim-sulfametoxazol and ciprofloxacin were the three most active antimicrobial agents (MIC 50: 0.5, 0.5 and 0.002 µg/mL, respectively).