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
Bacterial Spores
Category: Bacteria
Endospore-forming bacteria produce some of the most potent toxins known and are important pathogens in hospital-borne infections (Clostridium difficile) food contamination (Bacillus cereus, Clostridium botulinum), wound infestation (Clostridium perfringens, Clostridium tetani) and bioterrorism (Bacillus anthracis).
Bacilli and Clostridia spores form in response to unfavorable environmental conditions and can withstand extremes of heat, radiation, and chemical agents. The spore's durability is even more remarkable considering that dormant spores revert back to actively growing cells almost immediately after nutrients return to the environment. The intrinsic resistance and the ability to remain dormant for long periods make spores the perfect delivery vehicle for infectious diseases.
Further reading: The Ger Receptor Family from Sporulating Bacteria
Bacilli and Clostridia spores form in response to unfavorable environmental conditions and can withstand extremes of heat, radiation, and chemical agents. The spore's durability is even more remarkable considering that dormant spores revert back to actively growing cells almost immediately after nutrients return to the environment. The intrinsic resistance and the ability to remain dormant for long periods make spores the perfect delivery vehicle for infectious diseases.
Further reading: The Ger Receptor Family from Sporulating Bacteria
The Ger Receptor Family
Category: Bacteria
Ger receptor activation is the first committed step in the germination process. Ger receptors are encoded, in general, as tricistronic operons containing three protein-coding genes, the A-, B-, and C-subunits. However, some Ger receptor subunits are encoded as orphan monocistronic genes and yet other ger receptor operons encode duplicated subunit genes.
The A-subunit protein of Ger receptors consist of five or six predicted membrane-spanning domains, as well as large N- and C-terminal hydrophilic domains. A-subunit proteins share significant homology to SpoVAF, a late-sporulation protein with no known function. Intriguingly, Ger receptors have been shown to interact with proteins from the spoVA operon. Whether these interactions are relevant to spore germination remains to be elucidated.
Further reading: The Ger Receptor Family from Sporulating Bacteria
The A-subunit protein of Ger receptors consist of five or six predicted membrane-spanning domains, as well as large N- and C-terminal hydrophilic domains. A-subunit proteins share significant homology to SpoVAF, a late-sporulation protein with no known function. Intriguingly, Ger receptors have been shown to interact with proteins from the spoVA operon. Whether these interactions are relevant to spore germination remains to be elucidated.
Further reading: The Ger Receptor Family from Sporulating Bacteria