MICROBIAL INFECTIONS OF HUMANS(HUMAN MICROBIOLOGY CONTD..)
The genera Chlamydia and Rickettsia both contain species that cause human disease. Chlamydia
trachomatis causes trachoma and Rickettsia prowazekii causes typhus fever. Studies of the genomes of
these intracellular bacteria have yielded interesting patterns. By utilising host nutrients, these organisms
have lost the corresponding biosynthetic pathways; the amino acid synthesis pathways are absent with
the organisms choosing to utilise those of the host cell. Similarly the enzymes for synthesis of purines
and pyrimidines are largely absent. Energy requirements of these bacteria are still paramount but they
have lost the need for anaerobic glycolytic pathways as they now live in an aerobic environment. The
reduction in requirement for such enzymes results in the reduction in size of the genome of the bacteria.
The striking feature of these bacteria is the small genome size, around 1 megabase (1 Mb), roughly
equivalent to 800–900 genes, compared with free-living bacteria such as Esch. coli with a genome of 4.6
Mb in size. There are, however, pressures. The genomes of these intracellular parasites exhibit mutation
rates higher than free-living bacteria. One of the reasons is the loss of DNA-mismatch repair enzymes.
Another reason is the reduced opportunities for recombination or horizontal gene transfer with other
bacteria when choosing an obligate intracellular replication strategy. A similar problem is seen with
viruses. The intracellular existence will be dominated by the considerably larger host genome so it is
economical to lose any duplicated bacterial genes. Finally, the asexual, clonal replication with this
reduced genome repair kit will result in the accumulation of neutral and deleterious mutations, which
cannot be removed by selective pressure. Such a scenario might suggest that the organism has not got
much hope of survival. However, the organism can devote a dominant proportion of its genome to code
for features that favour persistence in the face of host defences.
As with obligate intracellular parasites, the asexual, clonal strategy results in a reduced genome with a
high proportion of mutated code. The residual genome codes for essential cell functions such as growth
and division. In contrast to obligate intracellular parasites, the host benefits from housing endosymbionts
such as Buchnera spp.because they synthesise amino acids that are available to the host as well. This
contrasts with Chlamydia and Rickettsia, both of which have lost the amino acid biosynthetic capability
and therefore compete for amino acids with the host. The gene loss has consequences for other cell
functions. An endosymbiont has no need for genes that code for antigenic variation and other defensive
host protection mechanisms. Likewise the organism has no need for mechanisms of entering and
leaving the host cell as it has become a stable partner. The conflict of interest between the organism and the host will result in a reciprocal exploitation that may result in mutualism or parasitism. One of the advantages of becoming an endosymbiont is efficient transmission from host to offspring (vertical transmission) and this benefits the host as well as the symbiont, whereas the genetic isolation and increased mutation rate might be seen as a disadvantage. The accumulation of deleterious mutations in a genetically isolated population (with almost no opportunities for recombination) is known as Muller’s ratchet. Endosymbionts will suffer from this
gradual loss of fitness through Muller’s ratchet. Conversely, the obligate intracellular parasite is usually
spread between unrelated hosts (horizontal transmission) and increases the chances of recombination,
and thus conflict between host and bacterium.