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The Rise of Antibiotics-Resistant Bacteria

A head louse in a washing machineEver since mankind came into this
world, it has been relentlessly assaulted and challenged and terrorized by the
multitudes of infections diseases that have since become a part of our lives. History
itself offers ghastly stories of vicious disease. For example, half the
population of Athens succumbed to plague in the year 430 BCE. Another plague -
perhaps smallpox - swept through the Roman Empire at around 165 CE, claiming
the lives of four to seven million people. That was not the last time Europe
suffered a plague attack. About a millennium later, in the 1340s, a scourge
descended upon India and China, killing 9 out of every 10 people, before making
its way to Europe, and later, Moscow and North Africa.

Mankind was never safe from the
threat of pestilence. In those days before drug therapy was properly developed,
infection was as good as a death sentence. People who contracted consumption
waited around for death’s hammer to strike. Houses sheltering victims of the
bubonic plague were boarded up, both patients and healthy people left to die
inside. And medical treatment, without benefit of science, did far more harm
than good, and hardly hampered the imminent spread of disease.

All of this changed in the 1920s
when Alexander Fleming, a Scottish bacteriologist doing research at St. Mary’s
Hospital in London, discovered the world’s first antibiotic, penicillin*.
A plate of staphylococci he had been cultivating had been contaminated with
mould*, which he found to be killing off the bacteria surrounding
it. Realizing the potential of penicillin as a weapon against infectious
disease, a team of British scientists at Oxford University, led by Howard
Florey, pushed penicillin research forward. By the end of World War II,
penicillin was available to everyone, and had saved more soldiers than the war
had claimed. Scientists eagerly began to look for other antibiotics-producing
organisms. Mortality rates dropped drastically. Infectious diseases caused by
bacteria were stopped in their tracks. Antibiotics had become the saviour of

Or had it?

Picture of girl with headache; bottle of Aspirin superimposed on top.

Today, penicillin is ineffective
against many of the diseases it had successfully combated sixty years ago. Some
microorganisms such as Staphylococcus
are resistant to three, maybe four different types of antibiotics, or maybe
more. Diseases we thought would never plague the developed world again, such as
the White Plague (tuberculosis), are back on the rise. And every day there is
another bacteria somewhere becoming resistant to antibiotics. The shield that
antibiotics has erected to separate us from the dangers of disease is suddenly
gone. We are no longer safe.

Why has this happened? Why have
antibiotics failed?

To understand all this, you need
to know how nature works. Evolution has always favoured the fittest in any
contest for survival. In the presence of selection (in this case, antibiotics),
mutant microorganisms that are resistant are given the opportunity to flourish
as their sensitive counterparts are wiped out by medicine. Mutant
microorganisms that may be dangerous and had caused the disease in the first
place, or harmless ones that had inhabited our bodies ever since we were born
into the world. The friendly ones become hostile, the hostile ones become even more
aggressive. And all of this has one factor in common: man.

Look around you and see the
horrors of antibiotics misuse. People who fail to finish their course of
antibiotics treatment actually encourage this phenomenon; those who abuse
antibiotics usage by consuming them as prophylactics or use them in agriculture
to promote animal growth and prevent disease*
only worsen the
situation in the long run. And then there’s the consumer market: antibacterial
paint, antibacterial soap, antibacterial mattresses. It’s a wonder that all the
bacterial of the world have not yet turned against us.

But even then mankind has been
cushioning itself from the truth, claiming that even if a certain bacteria
became resistant to a certain antibiotic, well, so what? Resistance is caused
by certain mutations in the bacteria’s genome, and everybody knows that the
frequency of mutations actually doing any good is so low as to be
insignificant. And anyway, we have so many different types of antibiotics that
even if a bacteria cannot be killed off by one, we’ll still have an arsenal
against it. Before the bacteria has accumulated resistance to more of these
drugs, we’ll have wiped it out with others!

Coming to terms with the truth

However, this reasoning was
shattered in 1963 when Dr. Tsutomo Watanabe announced this to the world:
bacteria can gain resistance to one, two, three, four (!) different antibiotics
AT ONE GO just by socializing with other
bacteria *. And because bacteria are promiscuous, this is not just
restricted to members of the same species.

You have to give these bacteria
some credit. Although they have only one chromosome that carries genes coding
for material that ensure their survival and growth, bacteria can also have any
number of free-floating closed circular DNA called plasmids. These are probably
not native to a bacterial cell, but are picked up from the environment, and can
replicate along with the bacterial chromosome. They do not carry some genes
needed by the bacteria under all conditions, but may contain information for
(among other things) physiological function, virulence and, most importantly,
resistance to antibiotics. These plasmids may be transferred from one bacteria
to another by conjugation*. Alternatively, a replicating bacterial
cell may pass on these plasmids to its daughter cells. These plasmids can
either remain as extrachromosomal matter, or integrate itself into the
bacterial chromosome. Also, Dr. Barbara McClintock’s discovery of ‘jumping
genes’ or transposons* led to the discovery that certain bacterial
genes could jump from one region of its chromosome to another, and between
bacterial cells. And if you thought that was bad, perhaps you should also
consider the fact that certain microbes can also easily absorb DNA from the
environment - DNA left behind by a ruptured cell, perhaps.

Think of the implications. Many different plasmids, maybe each one
carrying a resistance gene to a different antibiotic - all being transferred from one bacteria at one go. And many, many different species and families of
bacteria out there exchanging genes and gobbling up DNA.

Now multiple-drug resistant (MDR)
microbes are rampaging across our world, trading plasmids, giving rise to more
MDR microbes. They are most commonly found in hospitals; indeed, they are the
causative agents for a large number of nosocomial (hospital-acquired)
infections. Normally harmless bacteria that get along rather well with healthy
people attack and thrive in the bodies of the very sick or the very young or
old, whose immune systems are already overtaxed, common antibiotics no longer
effective in combating these microorganisms.

So what happens now in our war
against infectious disease and superbugs?

Fortunately for us, our resources
have not yet been exhausted in our race against microbes. There are reports
claiming that stopping the use of a particular antibiotic will, over time,
reverse the resistance to the antibiotic*. Microbes are parasites by
nature and, like most other creatures on Earth (barring man), are highly
adaptable. Those who inhabit other living creatures must make sure their hosts
stay alive long enough for them (the microbes) to multiply and spread to other
hosts. A microbe that kills off its host is not only ungrateful, it is not
likely to have many descendants either*. Therefore, in nature’s own
feedback loop, a microorganism will have inclination towards mild virulence.
And in this case, in the absence of selective forces, the trend will eventually
shift toward sensitive strains of microbes.

However, switching from drug to
drug is no long-term solution to this problem, and should not be allowed to
stand alone. To successfully fight antibiotics resistance, new classes of drugs must be developed or,
at the very least, analogs of existing antibiotics must be found. The second
approach will, needless to say, be much simpler, since it only involves
synthesizing drugs that have the same mode of action as existing ones but do
not possess the same weaknesses. The first approach (which would make Sissyphus
think twice about his task) involves isolating new compounds or custom-making
them in the lab to target specific parts of microorganisms. A number of these
new experimental drugs are designed to inhibit protein synthesis in the
bacterial cell, an example of which is the oxazolidinone family of drugs.

(It is somewhat ironic, however,
that nature has taught us that if there’s anything that microorganisms are good
at, it’s adapting to new environments. After all, they were
here first.)

Pharmaceautical research and drug
research must go hand-in-hand with
education if we are ever to win this war against pestilence. The general public
- and not just pharmacists and bacteriologists - must know at least the
essential facts about antibiotics and the hazards of antibiotics misuse. They
must learn that any weapon used too often and too much will inevitably, in the
long run, turn against the one who wields it along with multitudes of

But is this enough? When does our
war against antibiotics resistance - for it is
the antibiotics resistance phenomenon and not bacteria that we are battling -
end? The more anthropocentric of us may opine that we should get rid of the lot
of them (bacteria) before they do us any more harm; others may say that we had
it coming for messing around with nature’s delicate balance. Indeed, if we are
to opt for eradication, we will be forced to get rid of all bacteria because we
will claim that any given one is a potential threat to the survival of mankind.
However, we have all coevolved and coexisted with microorganisms to the point
that we can no longer get along without them synthesizing vitamins in our guts,
or digesting cellulose in ruminant animals. Who is to say that even with
increasingly developed and sophisticated technology we can find substitutes for
this essential part of our lives?

There are three possible futures
for mankind: (1) that we will eventually rid the earth of microorganisms, and
live a life of sterile existence, depending heavily on massive quantities of
synthesized vitamins and amino acids and other compounds that our bodies no
longer have the ability to make; (2) that the wantonly indiscriminate usage of
antibiotics and lack of awareness will send us plunging into another Dark Age,
helpless to stave off the waves of bacterial infections that our medicines have
become useless against, or (3) that mankind will eventually learn to manipulate
the fine balance of nature and domesticate the microbes so that the useful ones
become permanently fused to our lives and the harmful ones are removed of most
of their potency, thus becoming more of a general inconvenience than health

Which of these futures will
become reality? As one person, we may only be able do to pitifully little; as
one people, we may actually have enough momentum to push the destiny in our
direction of choice.

Books you may be interested to

If you are interested in seeing
the history of our world from a different point of view, read:

Margulis, L and D Sagan. 1986.
Microcosmos: Four billion years of microbial evolution. University of
California Press.

To know more about mankind’s
struggle with pestilence, check out:

Brookesmith, P. 1997. Future
plagues: Biohazard, disease and pestilence. Universal International Pty Ltd,
Australia. (I got the history facts for this article from there)

If you are an aspiring
microbiologist, or think that you would like to go into some branch of

Madigan, MT, JM Martinko, and J
Parker. 1997. Brock Biology of Microorganisms, 8th edition. Prentice
Hall International. (There may be newer editions in the market by now)

If you’d like to know more about

Conte, JE, Jr. 1995. Manual of
antibiotics and infectious disease, 8th ed. Williams and Wilkins,

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