Recombinant Probiotic Expressing Listeria Adhesion Protein Attenuates Listeria monocytogenes Virulence In Vitro

BACKGROUND: Bladder cancer is the ninth most common cancer in men. 70% of these tumors are classified as non-muscle invasive bladder cancer and those patients receive 6 intravesical instillations with Mycobacterium bovis BCG after transurethral resection. However, 30% of patients show recurrences after treatment and experience severe side effects that often lead to therapy discontinuation. Recently, another vaccine strain, Salmonella enterica typhi Ty21a, demonstrated promising antitumor activity in vivo. Here we focus on increasing bacterial retention in the bladder in order to reduce the number of instillations required and improve antitumor activity. OBJECTIVE: To increase the binding of Ty21a to the bladder wall by surface labeling of the bacteria with adhesion protein FimH and to study its effect in a bladder cancer mouse model. METHODS: Binding of Ty21a with surface-labeled FimH to the bladder wall was analyzed in vitro and in vivo. The antitumor effect of a single instillation of Ty21a+FimH in treatment was determined in a survival experiment. RESULTS: FimH-labeled Ty21a showed significant (p < 0.0001) improved binding to mouse and human cell lines in vitro. Furthermore, FimH labeled bacteria showed ∼5x more binding to the bladder than controls in vivo. Enhanced binding to the bladder via FimH labeling induced a modest improvement in median but not in overall mice survival. CONCLUSIONS: FimH labeling of Ty21a significantly improved binding to bladder tumor cells in vitro and the bladder wall in vivo. The improved binding leads to a modest increase in median survival in a single bladder cancer mouse study.

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The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion

Oncogene ◽

10.1038/s41388-021-01798-2 ◽

2021 ◽

Author(s):

Qiuping Xu ◽

Jingwei Zhang ◽

Brian A. Telfer ◽

Hao Zhang ◽

Nisha Ali ◽

...

Keyword(s):

Breast Cancer ◽

Protein Kinase ◽

Tumor Growth ◽

Focal Adhesion ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Metastatic Breast ◽

Adhesion Protein ◽

Focal Adhesion Protein

AbstractThere is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior.

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Effect of Gaseous Ozone on Listeria monocytogenes Planktonic Cells and Biofilm: An In Vitro Study

Foods ◽

10.3390/foods10071484 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1484

Author(s):

Felice Panebianco ◽

Selene Rubiola ◽

Francesco Chiesa ◽

Tiziana Civera ◽

Pierluigi Aldo Di Ciccio

Keyword(s):

Listeria Monocytogenes ◽

In Vitro Study ◽

Planktonic Cells ◽

Free Living ◽

Biofilm Inhibition ◽

Additional Tool ◽

Complete Inactivation ◽

Gaseous Ozone ◽

Food Borne

Among food-borne pathogens, Listeria monocytogenes continues to pose concerns to food business operators due to its capacity to form biofilm in processing environments. Ozone may be an eco-friendly technology to control microbial contaminations, but data concerning its effect on Listeria monocytogenes biofilm are still limited. In this study, the effect of gaseous ozone at 50 ppm on planktonic cells and biofilm of reference and food-related Listeria monocytogenes strains was evaluated. Ozone caused a reduction in microbial loads of 3.7 ± 0.4 and 3.9 ± 0.4 Log10 CFU/mL after 10 and 30 min, respectively. A complete inactivation of planktonic cells after 6 h of treatment was observed. Biofilm inhibition and eradication treatments (50 ppm, 6 h) resulted in a significant decrease of the biofilm biomass for 59% of the strains tested, whilst a slight dampening of live cell loads in the biofilm state was observed. In conclusion, gaseous ozone is not sufficient to completely counteract Listeria monocytogenes biofilm, but it may be useful as an additional tool to contrast Listeria monocytogenes free-living cells and to improve the existing sanitization procedures in food processing environments.

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The in vitro inhibition of growth of intracellular Listeria monocytogenes by lymphocyte products

Cellular Immunology ◽

10.1016/0008-8749(73)90050-6 ◽

1973 ◽

Vol 9 (3) ◽

pp. 353-362 ◽

Cited By ~ 13

Author(s):

Tobi Jones ◽

Guy P. Youmans

Keyword(s):

Listeria Monocytogenes ◽

Inhibition Of Growth ◽

In Vitro Inhibition

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Stimulation of activated rat T cells in vitro by Listeria monocytogenes antigens

Infection and Immunity ◽

10.1128/iai.29.3.1102-1110.1980 ◽

1980 ◽

Vol 29 (3) ◽

pp. 1102-1110

Author(s):

M C Woan ◽

U K Forsum ◽

D D McGregor

Keyword(s):

T Cells ◽

Listeria Monocytogenes ◽

Soluble Extract ◽

In Vitro Proliferation ◽

Surface Immunoglobulin ◽

Peripheral T Cells ◽

Proliferation Of Lymphocytes ◽

Antigen Presenting ◽

Stimulation Of

A soluble extract of Listeria monocytogenes bound firmly and in similar amounts to a variety of rat cells. Cells that bound this material differed in their capacity to stimulate the in vitro proliferation of lymphocytes obtained from the thoracic duct of Listeria-immune donors. The capacity of cells to serve as antigen-presenting cells in this system coincided or closely overlapped the expression on these cells of an Ia antigen-like structure. Three lines of evidence indicate that T cells respond to L. monocytogenes antigen: the responder cells are members of a nylon-wool nonadherent population that lacks readily detectable surface immunoglobulin; they express determinants recognized by the W3/25 monoclonal antibody (a surface marker of rat peripheral T cells); and they are stimulated optimally by L. monocytogenes antigen when the latter is displayed on cells that share a haplotype with the responder lymphocytes.

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