Dataset Information

Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

ABSTRACT: Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do.

SUBMITTER: Yu B

PROVIDER: S-EPMC3365283 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

Yu Bin B Yang Mei M Shi Lei L Yao Yandan Y Jiang Qinqin Q Li Xuefei X Tang Lei-Han LH Zheng Bo-Jian BJ Yuen Kwok-Yung KY Smith David K DK Song Erwei E Huang Jian-Dong JD

Scientific reports 20120601

Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therap ...[more]

PMID: 22666539

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Project description:BACKGROUND: Motility is an important component of Salmonella enterica serovar Typhimurium (ST) pathogenesis allowing the bacteria to move into appropriate niches, across the mucus layer and invade the intestinal epithelium. In vitro, flagellum-associated motility is closely related to the invasive properties of ST. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is widely prescribed for the prophylaxis and treatment of diarrheal diseases caused by bacteria or antibiotics. In case of Salmonella infection, S.b-B has been shown to decrease ST invasion of T84 colon cell line. The present study was designed to investigate the impact of S.b-B on ST motility. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed on human colonic T84 cells infected by the Salmonella strain 1344 alone or in the presence of S.b-B. The motility of Salmonella was recorded by time-lapse video microscopy. Next, a manual tracking was performed to analyze bacteria dynamics (MTrackJ plugin, NIH image J software). This revealed that the speed of bacterial movement was modified in the presence of S.b-B. The median curvilinear velocity (CLV) of Salmonella incubated alone with T84 decreased from 43.3 µm/sec to 31.2 µm/sec in the presence of S.b-B. Measurement of track linearity (TL) showed similar trends: S.b-B decreased by 15% the number of bacteria with linear tract (LT) and increased by 22% the number of bacteria with rotator tract (RT). Correlation between ST motility and invasion was further established by studying a non-motile flagella-deficient ST strain. Indeed this strain that moved with a CLV of 0.5 µm/sec, presented a majority of RT and a significant decrease in invasion properties. Importantly, we show that S.b-B modified the motility of the pathogenic strain SL1344 and significantly decreased invasion of T84 cells by this strain. CONCLUSIONS: This study reveals that S.b-B modifies Salmonella's motility and trajectory which may account for the modification of Salmonella's invasion.

Dataset Information

Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

Publications

Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain.

Similar Datasets

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