Salmonella Typhimurium
Salmonella and Cancer
Salmonella as the paradigm for bacterial therapy of cancer: A progress report
from Robert M. Hoffman writing in Salmonella: From Genome to Function
For over 300 years it has been observed that cancer patients who became infected with bacteria sometimes experienced spontaneous remission of their cancer. Recently, there have been attempts to develop cancer treatments by using tumor-targeting bacteria. Anaerobic microorganisms, such as Clostridium, that preferentially grow in necrotic tumor areas have mostly been used. However, the resulting tumor killing was, at best, limited. Salmonella was originally developed as an antitumor agent by attenuating the bacteria with multiple mutations, including auxotrophs. These multiple auxotrophs appeared to direct the bacteria to the metastatic areas of tumors where more nutrients are available. We have developed a more effective bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella enterica serovar Typhimurium containing only two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a safe treatment. The S. Typhimurium A1-R mutant, which is auxotrophic for leucine and arginine and had been selected for high antitumor virulence, was effective as monotherapy against human prostate and breast tumors that had been orthotopically implanted in nude mice. The approach described here, where bacterial monotherapy effectively treats primary and metastatic tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy. Exploitation of the tumor-killing capability of Salmonella has great potential for a new paradigm of cancer therapy.
Further reading: Salmonella: From Genome to Function
from Robert M. Hoffman writing in Salmonella: From Genome to Function
For over 300 years it has been observed that cancer patients who became infected with bacteria sometimes experienced spontaneous remission of their cancer. Recently, there have been attempts to develop cancer treatments by using tumor-targeting bacteria. Anaerobic microorganisms, such as Clostridium, that preferentially grow in necrotic tumor areas have mostly been used. However, the resulting tumor killing was, at best, limited. Salmonella was originally developed as an antitumor agent by attenuating the bacteria with multiple mutations, including auxotrophs. These multiple auxotrophs appeared to direct the bacteria to the metastatic areas of tumors where more nutrients are available. We have developed a more effective bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella enterica serovar Typhimurium containing only two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a safe treatment. The S. Typhimurium A1-R mutant, which is auxotrophic for leucine and arginine and had been selected for high antitumor virulence, was effective as monotherapy against human prostate and breast tumors that had been orthotopically implanted in nude mice. The approach described here, where bacterial monotherapy effectively treats primary and metastatic tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy. Exploitation of the tumor-killing capability of Salmonella has great potential for a new paradigm of cancer therapy.
Further reading: Salmonella: From Genome to Function
Phages of Salmonella
Typing phages and prophages of Salmonella
from Wolfgang Rabsch, Sandra Truepschuch, Daniel Windhorst and Roman G. Gerlach writing in Salmonella: From Genome to Function:
Most Salmonella strains contain prophages or remnant phages and release them spontaneously. Special bacteriophages were developed and used in phage typing systems for epidemiological work all over the world since 1947 to control salmonellosis. This method provides fast and inexpensive characterization of frequent serovars such as S. Typhimurium or S. Typhi on the sub-serovar level and is especially useful for primary analysis before investigation by other, more expensive molecular techniques such as sequencing. Prophages are themselves not only variable elements in a chromosome but also variable by module exchange within the prophage genome, thus providing a high discriminating power. The availability of several genome sequences of different Salmonella serovars has recently led to the identification of new prophage-like elements. The prophages present in serovars Typhimurium, Enteritidis and Typhi are discussed. Salmonella phages frequently carry foreign DNA, so called morons. These morons are not necessary for phage functions but provide a benefit for the host. A list of some new morons found in different Salmonella serovars is presented. Recently, a monophasic variant of S. Typhimurium mainly belonging to Anderson phage type DT193 has become one of the dominant causes of salmonellosis in Germany and other European countries. These strains with the antigenic formula 4,[5],12:i:- do not express the 2nd phase flagellum. Investigation of their prophage attachment sites showed that the sites for Gifsy-1, Gifsy-2 and ST64B were occupied by the respective prophages. In about 90% of the monophasic DT193 strains the P22/ST64T attachment site was occupied by a novel 18.4 kb fragment, containing several open reading frames with significant similiarity to phage-related genes.
Further reading: Salmonella: From Genome to Function | Bacteriophage: Genetics and Molecular Biology
from Wolfgang Rabsch, Sandra Truepschuch, Daniel Windhorst and Roman G. Gerlach writing in Salmonella: From Genome to Function:
Most Salmonella strains contain prophages or remnant phages and release them spontaneously. Special bacteriophages were developed and used in phage typing systems for epidemiological work all over the world since 1947 to control salmonellosis. This method provides fast and inexpensive characterization of frequent serovars such as S. Typhimurium or S. Typhi on the sub-serovar level and is especially useful for primary analysis before investigation by other, more expensive molecular techniques such as sequencing. Prophages are themselves not only variable elements in a chromosome but also variable by module exchange within the prophage genome, thus providing a high discriminating power. The availability of several genome sequences of different Salmonella serovars has recently led to the identification of new prophage-like elements. The prophages present in serovars Typhimurium, Enteritidis and Typhi are discussed. Salmonella phages frequently carry foreign DNA, so called morons. These morons are not necessary for phage functions but provide a benefit for the host. A list of some new morons found in different Salmonella serovars is presented. Recently, a monophasic variant of S. Typhimurium mainly belonging to Anderson phage type DT193 has become one of the dominant causes of salmonellosis in Germany and other European countries. These strains with the antigenic formula 4,[5],12:i:- do not express the 2nd phase flagellum. Investigation of their prophage attachment sites showed that the sites for Gifsy-1, Gifsy-2 and ST64B were occupied by the respective prophages. In about 90% of the monophasic DT193 strains the P22/ST64T attachment site was occupied by a novel 18.4 kb fragment, containing several open reading frames with significant similiarity to phage-related genes.
Further reading: Salmonella: From Genome to Function | Bacteriophage: Genetics and Molecular Biology