I proposed the following discussion in this paper.
The terms dormancy, persistence and latency have
been used interchangeably in the TB literature generally to refer to the non
multiplying state of Mtb, tolerance to TB drugs or an infection without active
disease. Although the three conditions are distinct biological phenomena from
the host’s perspective, I propose a unified phenomenon when considered from the
pathogen’s perspective. Dormancy is a physiological state of Mtb characterized
by cessation in proliferation whether in an artificial culture medium or in a
host. Persistence describes the tolerance by a subpopulation of bacilli to the
bactericidal effects of drugs [Gomez & McKinney, 2004; Lewis, 2007]. This
tolerance is phenotypic and transient, because the bacilli remain genetically
susceptible to the drugs. Latency is the presence of Mtb infection in a host
without clinical symptoms of TB. One-third of the human population is infected
with Mtb, but the majority of people who harbor a latent infection lack the
clinical symptoms of TB [Dye, 1999].
By contrast, dormancy, persistence and latency
could be fundamentally the same from the pathogen’s perspective: dormancy is a
physiological state of arrested growth, persistence is survival in the presence
of stress from drugs that are administered exogenously and latency is survival
in the presence of stress from immune response, which could be in the form of
small toxic molecules produced by the host. The Mtb bacilli are affected by
toxic molecules whether it is host generated or provided exogenously and in response
remain dormant. The treatment of TB is one of the most cumbersome for the
patient because it requires a daily intake of a combination of drugs for at
least six months. Although >99% of Mtb are killed during the first two weeks
[Jindani, 2003], prolonged treatment is required to kill the persisting
population that is thought to transiently tolerate the drugs [Gomez &
McKinney, 2004; Lewis, 2007]. Therefore, the persister population is highly
significant because it is widely believed that the duration of treatment can
only be reduced by killing this population sooner.
My colleague Prof. Jacques Grosset's response:
Dear Gyanu,
It is a reasonable attempt but I would like to make two comments: (i)
For me, dormancy is an anthropomorphic term convenient to describe
multiple puzzling conditions in which bacteria are alive but not multiplying.
In other words, using it permits to escape any reflection on the
involved mechanisms; (ii) For the same reason , I wonder the accuracy of your
sentence “ I propose a unified
phenomenon when considered from the pathogen’s perspective” because it is
anthropomorphism to refer to pathogen’s perspective that suggests that
the pathogen is clever, has choice, is making decision, etc. , something that
is frequently heard in top brass circles and is 100% scientifically doubtful.
The worst example of this type of thinking is to consider that the bug is so
clever that it develops resistance to drugs and so on. The book of the Jacques
Monod on “Chance and necessity" should be read and re-read.
Hi Jacques,
I agree with what you say. It is also my understanding that bacteria (or
any other organism including humans) do not have a genetic will but it is the
environmental conditions that they are in that selects the fittest to survive
and proliferate under the prevailing conditions. I have always maintained (and
taught formal classes) that statements such as 'bacteria will become resistant
to drugs' are illogical because by it one means that bacteria (or any
organism's genetic phenomenon) will change as needed. This is too Lamarckian
and has been disproved. I maintain that ' mutation of the genome is an inherent
fact of DNA polymerase activity and therefore irrespective of stresses there
will be mutantions'. The environmental stresses will only allow the fittest to
selectively proliferate'. By "pathogen's perspective" I meant from
the perspective of "pathogen's biological machinery which cannot
think" but face the stresses. I think we both are saying the same thing,
but it must be my choice of words that puzzled you. Your response provides
additional clarification to this topic. Thank you. - Gyanu