Mutations of Bacteria from Virus Sensitivity to Virus Resistance

When a pure bacterial culture is attacked by a bacterial virus, the culture will clear after few hours due

to damage of sensitive cells by the virus. Though, the culture will again turbid after few hours, or some

days. The reason is to growth of bacterial variant which are resistance to virus. The variant may be

differing from original strain in morphological or metabolic characteristics, or in serological type or in

colonial type. BURNET’S worked on isolations of colonies, morphologically specific to the

accumulation of virus, which proved resistant. In the first generation of the resistant variant, which can

survive after virus attack called as “original variant”.

They formulated three alternative hypotheses regarding these original variants are

a) Hypothesis of mutation to immune - The original variants were resistant before the virus was

added, and their offspring didn’t contact with virus. In this hypothesis the virus did not

interact with the original variants. The origin of which must be attributed to “mutations” that

occur quite independently of the virus.

b) Hypothesis of acquired immunity – The original variants interacts with the virus, but

survived the attack. After that they inquire into the affecting cause which effects the survival

of these bacteria in contradistinction to the succumbing ones. After that they proposed two

alternative hypotheses which are Hypothesis of acquired immunity of hereditarily predisposed

individuals and Hypothesis of acquired immunity- hereditary after infection.

This alternative hypothesis may be grouped by first considering the origin of the hereditary differences.

Then they subdivided the first alternative hypothesis that whether the original variants do or don’t

interact with the virus and these formulated two hypotheses as follows

I. First hypothesis (mutation)= There is a finite probability for any bacterium to mutate

during its life time from sensitive to resistant. These mutants will be resistant, unless

reverse mutation occurs. Resistant means the bacteria would not be killed by exposure to

virus, but the possibility for the virus is still open.

 II. Second hypothesis (acquired hereditary immunity): the rate of probability of bacterium to

survive after attack by the virus. Survival shows immunity to the individual or offspring

too.

In the mutation hypothesis, the mutation to resistance may occur any time prior to the addition of

virus, culture may contain the clones of resistant bacteria which are in many sizes. The two main

differences may be derived from the hypothesis

In the first hypothesis, if the individual cells of a very large number of microcolonies, which contains

only a few bacteria, were examined for resistance, a pronounced correlation between the types found in

a single colony would be expected on the mutation hypothesis, while a random distribution of resistant’s

would be expected on the hypothesis of acquired hereditary immunity. And in the second one, the

hypothesis of resistance due to mutation, the proportion of resistant bacteria should increase with time.

They aimed to analysis the probability distributions of the number of resistant bacteria to be expected

on the hypothesis of acquired immunity and on the hypothesis of mutation.

The probability to obtaining the seven resistant bacteria by (a) seven mutations during the last

generation; (b) three mutations during the last generation and two mutations one generation back (c)

three mutations during the last generation and one mutation two generations back (d) one mutation

during the last generation and three mutations one generation back (e) one mutation during the last

generation, one mutation one generation back and one mutation two generations back. The probability

these events depends only on the mutation rate and on the final number of bacteria.

They used bacterial virus alpha and their host E. coli B. Secondary cultures after apparently complete

lysis of B by virus shows within a few hours from the time of clearing. They consist of cells which are

resistant to the action of virus alpha, but sensitive to a series of other viruses which are active on B. In

this paper they didn’t studied any trace of virus in the pure culture which are resistant bacteria. Further

these resistant strains considered as non-lysogenic. Morphologically at least two types of colonies of

resistant bacteria may be distinguished while studying. In The first type of colony is similar to the type

produced by the sensitive strain both in size and in the character of the surface and of the edge and in
the second type of colony is much smaller and translucent. The difference in colony type is maintained

in subcultures. In their experiments they wanted to study the fluctuations of the numbers of resistant

bacteria found in cultures of sensitive bacteria. In the method of testing did not involve any

unrecognized variables, which caused the number of resistant colonies to vary from plate to plate or

from sample to sample.

They proved that in their case the resistance to virus is due to a heritable change of the bacterial cell

which occurs independently of the action of the virus. The proportion of mutant organisms in a culture

and the mutation rate are far smaller in our case than in other studied cases of heritable bacterial

variation. The virus resistant variants do not exhibit any striking correlated physiological changes. It is

also conceivable that the loss occurs upon contact of bacteria with virus, since it is detected only after

such contact. It may be more likely that the loss of surface affinity to virus is a direct effect of the

mutation. The distribution of the numbers of virus resistant bacteria in series of similar cultures of a

virus-sensitive strain has been analyzed theoretically on the basis of two current hypotheses concerning

the origin of the resistant bacteria. The distribution has been studied experimentally and has been found

to conform with the conclusions drawn from the hypothesis that the resistant bacteria arise by mutations

of sensitive cells independently of the action of virus.