A repetitive mutation and selection system for bacterial evolution to increase the specific affinity to pancreatic cancer cells

PloS One
Masaki Osawa

Abstract

It is difficult to target and kill cancer cells. One possible approach is to mutate bacteria to enhance their binding to cancer cells. In the present study, Gram-negative Escherichia coli and Gram-positive Bacillus subtilis were randomly mutated, and then were positively and negatively selected for binding cancer vs normal cells. With repetitive mutation and selection both bacteria successfully evolved to increase affinity to the pancreatic cancer cell line (Mia PaCa-2) but not normal cells (HPDE: immortalized human pancreatic ductal epithelial cells). The mutant E. coli and B. subtilis strains bound to Mia PaCa-2 cells about 10 and 25 times more than to HPDE cells. The selected E. coli strain had mutations in biofilm-related genes and the regulatory region for a type I pilus gene. Consistent with type I pili involvement, mannose could inhibit the binding to cells. The results suggest that weak but specific binding is involved in the initial step of adhesion. To test their ability to kill Mia PaCa-2 cells, hemolysin was expressed in the mutant strain. The hemolysin released from the mutant strain was active and could kill Mia PaCa-2 cells. In the case of B. subtilis, the initial binding to the cells was a weak interaction of th...Continue Reading

References

Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C G Cupples, J H Miller
Apr 20, 2000·The Journal of Clinical Investigation·M SznolI King
Nov 14, 2000·The American Journal of Pathology·H OuyangM S Tsao
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·L H DangB Vogelstein
Jul 23, 2002·Human Gene Therapy·Ivan KingLi-Mou Zheng
Dec 28, 2002·Genes & Development·Angelica Abanes-De MelloKit Pogliano
Mar 26, 2003·The American Journal of Pathology·Christine A Iacobuzio-DonahueMichael Goggins
Aug 16, 2003·The Journal of Biological Chemistry·Hendrik SzurmantGeorge W Ordal
May 5, 2006·Journal of Bacteriology·Juliane OllingerJohn D Helmann
Apr 24, 2007·International Journal of Medical Microbiology : IJMM·Jochen StritzkerAladar A Szalay
Jul 17, 2007·PLoS Pathogens·Danelle S EtoMatthew A Mulvey
Sep 9, 2008·Trends in Molecular Medicine·Thomas KlonischMarek Los
Dec 23, 2008·FEBS Letters·Matthias HusmannSucharit Bhakdi
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniel SchultzJosé N Onuchic
Dec 25, 2009·FEMS Microbiology Reviews·Daniel López, Roberto Kolter
Jul 28, 2013·SpringerPlus·Uwe Karsten, Steffen Goletz
Dec 18, 2013·Proteomics·Maja N ChristiansenNicolle H Packer
Feb 5, 2014·Nature Reviews. Urology·Gil Redelman-SidiBernard H Bochner
Mar 5, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adam T St JeanNeil S Forbes
Apr 15, 2015·International Journal of Cancer. Journal International Du Cancer·Christian SternSiegfried Weiss

❮ Previous
Next ❯

Datasets Mentioned

BETA
PRJNA16351

Methods Mentioned

BETA
PCR
Illumina sequencing
xenograft

Related Concepts

Related Feeds

ATP Synthases

ATP synthases are enzymes located in the inner mitochondrial membrane that catalyze the synthesis of ATP during cellular respiration. Discover the latest research on ATP synthases here.

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.