ABSTRACT
@#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.
ABSTRACT
Objective To investigate the antibiotic susceptibilities and the profiles of virulence genes of clinically isolated Salmonella enterica serovars Schwarzengrund ( S. Schwarzengrund) strains for bet-ter understanding the epidemiological trend of this type of non-typhoidal Salomonella and to provide guide-lines for the prevention and treatment of S. Schwarzengrund infection. Methods Stool samples and clinical data of patients with acute diarrhea who received treatment in the Second Hospital of Tianjin Medical Univer-sity during May, 2014 to October, 2014 were collected for this study. Enrichment culture and biochemical identification were used to isolate and identify the S. Schwarzengrund strains. The isolated strains were fur-ther analyzed with serotyping analysis, drug susceptibility test, pulsed field gel electrophoresis ( PFGE) and multiple locus sequence typing ( MLST ) . The representative genes carried by Salmonella pathogenicity islands (SPI) 1-5, SPI regulators and virulence plasmids were amplified by PCR. The coding genes of CdtB-islet, which were cdtB, pltA and pltB were amplified and sequenced. Results In total, 16 (14. 8%) out of 108 non-typhoidal Salmonella strains were identified as S. Schwarzengrund strains and all of them were sus-ceptible to 11 kinds of antibiotics such as fluoroquinolone, ampicillin, ceftriaxone and trimethoprim-sulfame-thoxazole. PFGE categorized the 16 S. Schwarzengrund strains into 3 clusters including A clone ( 14 strains), B clone (1 strain) and C clone (1 strain). The strains that isolated from 8 patients who ate the same food belonged to one cluster ( A clone ) , suggesting that it was an outbreak of infection. The 16 S. Schwarzengrund strains showed identical MLST type, which was ST241. The representative genes carried by SPI1-5 ( invA, sitC, hilA, sseL, sifA, mgtC, siiE and sopB) , the regulatory gene ( phoP) and the cytole-thal distending toxin islet (CdtB-islet) coding genes (cdtB, pltA and pltB) were positive, while the genes carried by virulence plasmids (pefA, prot6E and spvB) were negative. The similarities in CdtB-islet coding genes and amino acids sequences between Salmonella typhi and S. Schwarzengrund strains in this study were more than 97% and 98%, respectively. Conclusion In this study, polyclonal S. Schwarzengrund strains of ST241 type were isolated from the patients. They were susceptible to common antibiotics, but carried the virulence genes contained in SPI1-5 and CdtB-islet coding genes and might cause an outbreak of infection. Attention should be paid to the tendency and threat of clinical S. Schwarzengrund infection and continuous surveillance and investigation should be performed.
ABSTRACT
HilA is a central regulator of Salmonella pathogenicity island 1 (SPI1), which is necessary for host invasion by Salmonella and induction of gastroenteritis. The iagB lies downstream of hilA and is thought to be co-transcribed with hilA, but iagB expression has not yet been analyzed directly. In this study, iagB expression in various mutant strains was measured to determine whether the expression pattern was similar to that of hilA. A β-galactosidase assay revealed that iagB expression was greater under shaking than standing culture condition. iagB expression was decreased in relA/spoT and ihfB mutants but not in luxS mutant, in line with previous reports on hilA expression. The hilA and iagB mRNA levels decreased by approximately 2-fold in arcA mutant grown aerobically and increased by approximately 10-fold in fnr mutant grown anaerobically. Although the fold changes in hilA and iagB mRNA level differed in hfq mutant strain, the patterns of time- and Hfq-dependent regulation were similar for both genes. Thus, iagB and hilA exhibited similar expression patterns in various mutational backgrounds and under different growth condition.