Summary While not negating the seriousness of tuberculosis and the need to prevent and combat the disease
effectively, the large percentage of infected, apparently healthy individuals who harbour latent infections warrants
consideration whether an endosymbiotic relationship is being established between mycobacteria and man. By means of
a gene decay process eliminating their most metabolically important pathogenic genes associated with an increasing
need for host gene products during prolonged intracellular survival, mycobacteria appears to be undergoing a process
of establishing a less dangerous relationship with its host. To have tolerated this relationship over time, humans must
have benefited. This is suggested to have occurred via changes in DNA higher order structure altering combinatorially
regulated gene expression allowing increased cerebrodiversity. It can be expected that, beyond a certain threshold,
negative effects ensued, leading to neuropathology and increased susceptibility for certain psychiatric disorders.
These processes have probably been happening since the earliest contact with mycobacteria, but recently may have
become modified by the emergence of epidemic tuberculosis and waves of increased oxidative stress following the
circumstances associated with the Industrial Revolution and the more recent AIDS pandemic. The organism seems to
have uniquely exploited the normal stress reaction of the host. Genomic stresses include changes associated with
glucocorticoid effects as well as upregulated reactive oxygen species and stress/(heat shock) protein production, the
latter two of which result in host cell cycle delay. Subsequently replication dependent chromosomal fragile sites
appear in the host genome and together with upregulated chaperonins and mobile element activation, the scene is set
for sequence exchange between the organism and host. If proven, these events raise the possibility of modifying
chromatin epigenetically to retain the proposed advantages while silencing pathogenicity factors.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:tut/oai:encore.tut.ac.za:d1000797 |
| Date | 02 February 2006 |
| Creators | Gericke, GS |
| Publisher | Elsevier |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | |
| Rights | Elsevier |
| Relation | Medical Hypotheses |
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