RESUMO
This review considers available evidence for mechanisms of conferred adaptive advantages in the face of specific infectious diseases. In short, we explore a number of genetic conditions, which carry some benefits in adverse circumstances including exposure to infectious agents. The examples discussed are conditions known to result in resistance to a specific infectious disease, or have been proposed as being associated with resistance to various infectious diseases. These infectious disease-genetic disorder pairings include malaria and hemoglobinopathies, cholera and cystic fibrosis, tuberculosis and Tay-Sachs disease, mycotic abortions and phenylketonuria, infection by enveloped viruses and disorders of glycosylation, infection by filoviruses and Niemann-Pick C1 disease, as well as rabies and myasthenia gravis. We also discuss two genetic conditions that lead to infectious disease hypersusceptibility, although we did not cover the large number of immunologic defects leading to infectious disease hypersusceptibilities. Four of the resistance-associated pairings (malaria/hemogloginopathies, cholera/cystic fibrosis, tuberculosis/Tay-Sachs, and mycotic abortions/phenylketonuria) appear to be a result of selection pressures in geographic regions in which the specific infectious agent is endemic. The other pairings do not appear to be based on selection pressure and instead may be serendipitous. Nonetheless, research investigating these relationships may lead to treatment options for the aforementioned diseases by exploiting established mechanisms between genetically affected cells and infectious organisms. This may prove invaluable as a starting point for research in the case of diseases that currently have no reliably curative treatments, e.g., HIV, rabies, and Ebola.
RESUMO
This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a "Trojan horse" for future oral biotherapy of brain cancer.
