A Microbial Arms Race - InfoBarrel

The romanticized notion that life a hundred or two hundred years ago was natural and healthy is a
crock. Life before antibiotics was not an easy life. Infant mortality rates were astronomical, people
did not live nearly as long nor as well and a simple scratch could maim or kill you if the medicine of
the times did not do it first. Even the food in the eighteenth and nineteenth centuries was
adulterated and contaminated with microbes, parasites and chemicals.
The discovery of antibiotics was a huge leap forward in modern medicine. For nearly seventy years
antibiotics have been critical in the fight against infectious disease caused by bacteria and other
microbes. Before then, one could lose limbs, become disabled or even die from an infection.
Bacteria, however, have proven themselves much more creative and adaptive than we could have
ever imagined developing resistance to antibiotics at an ever-increasing rate.
Skin and wound infections, gonorrhea, tuberculosis, pneumonia, septicemia, strep throat and
childhood ear infections are just a few of the diseases that are now difficult to treat with antibiotics.
Seventy percent of bacteria that cause infections in hospitals are resistant to at least one of the
drugs, or antibiotics, most commonly used to treat it.
Antibiotics are a bedrock of modern medicine. Without them we risk returning to the days of dark
age medicine, a post-antibiotic era. Doctor Margaret Chan, Director of World Health Organization
(WHO) says that

A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common
as strep throat or a childs scratched knee could once again kill[1]

Bacteria are likely, the oldest life form on earth. They've been around for anywhere from three
billion years to seven billion years. They are single-celled organisms, with no nucleus and no other
membrane bound organelles, they're literally the simplest living organism. Yet they continue to
match our efforts to eradicate them or control them. Should be no surprise that they have learned a
few tricks to surviving over the billions of years they've been here.
This problem of antibiotic resistance was recently highlighted in a recent WHO (World Health
Organization) report which detailed antimicrobial resistance levels world-wide, they called for a
'concerted effort to tackle the issue' which is now called a global health security risk. Resistance to
medicines was once only seen in poorer countries due to a number of factors, but today antibiotic
resistant bacteria are in every corner of the globe even in notoriously strict New Zealand where you
need an x-ray to get into the country.
With growing frequency we hear more and more about something called a superbug. Sometimes it is
overseas in a country you have only seen in a National Geographic magazine, other times it is
knocking at your front door. Main stream media headlines include words like lethal, fatal, infectious
disease nightmare and deadly. Documentaries talk of how dangerous they are, what we are doing
and discuss why we are still losing this battle with a small, invisible to the naked eye microbe.

While we do not create the laws of nature, we do not always like them, think they are fair or even
want to follow them - but to better control infectious disease, we have to at least understand the
rules of the 'game'.
What makes a microbe a 'super bug' and just how 'super' are we talking? Why not just make
stronger medicine? Why the sudden increase in these antibiotic resistant bacteria? Where are they
coming from? How do I avoid and prevent them? What are we doing about them and how are
societies in general, kept safe?.
This article is an exploratory look at mankind's war with microbes, why are we still losing?.
A Medical CinderellaDiscovery of Penicillin
There was a time in human history when travelling the lands required months, life expectancy, for
both sexes, averaged out to the late thirties and early forties, where infections were once the
number one cause of death and populations were smaller and in isolated communities.
When aggressive disease (or microbes) did rear its ugly headit really had no where to go after
infecting the small, mostly isolated community it was in. End of the line for the microbe. No fresh
bodies to infect, it can't spread or live on.
Today's growing world populations are not only immense in size but tightly connected around the
globe. Travelling around the globe takeshours, not weeks and months. There is a growing elderly
population in many countries as well as ones consisting of immune weakened people.
As we learned to travel faster (airplanes), live longer (antibiotics) and live larger (cities) ... we were
also upsetting the evolutionary balance of a microbes ability to infect something, or its virulence. By
trying to destroy the microbe, it learned to defend itself and how to attack/survive better. Despite
the simplicity behindabacteria, they have been around for a very long time, for a reason.
Too many people today do not remember nor know of a life before penicillin or antibiotics.
Penicillin was the first antibiotic discovered and it saved thousands of lives when it was used in
World War Two. Discovered by Alexander Fleming in 1929, it was not mass-produced till the early
1940's, and was in development stages before then.
Once it was mass-produced, it became the wonder drug prescribed for everything, from sniffles to
sore muscles. Over the years it even found its way into animal feed in low doses regularly given to
them to ensure 'good health' and to prevent future diseases before they even happen.
Penicillin works by inhibiting the growth of bacteria, thus killing it. If you did not kill all of the
bacteria for some reason, such as not taking it for the full length of timeprescribed, the surviving
bacteria were resistant to penicillin. The same resistance isseen when bacteria are exposed to lower
doses.
Alexander Fleming discovered early on that the bacteria the antibiotics were inhibiting showed
resistance under those same conditions, yet it was never taken into consideration when antibiotics
were becoming more misused and abused. There are only a limited number of antibiotics and and an
unlimited amount of microbes, each time microbes are exposed to a different antibiotic they can
become resistant.

Penicillin resistant Staphylococcus appeared in 1940, despite having not been on the market for
public consumption. Tetracycline made its way to the physicians war chest in 1950, Shigella bacteria
resistant to tetracycline emerged 9 years later. Erythromycinhit the markets in 1953 and by 1968
the resistance was seen in strep[2].
It only got worse as antibiotics became affordable and their use increased greatly. Methicillincame
out in 1960, resistanceby 1962, Levofloxacin came next in 1996 and the resistant bugs were outthat
same year. The story is the same for nearly every existing antibiotic.
Today we have multi-resistant bacteria, superbugs or just antibiotic resistant bacteria. This means,
that in many cases at least one antibiotic no longer works, and in the cases of multi-drug resistant
bacteria or as the media calls them, superbugs, they are resistant to numerous classes of antibiotics.
Whats and Hows of AntibioticsModus Operandi
Bacteria are very simple in structure, despite their complex ways (resistance for one). Different
families or classes of antibiotics have different methods (modes of action) of interrupting or killing
bacteria, based on the nature of their structure and whether or not they attack or inhibit cell walls,
ribosomes or DNA.

Beta-Lactam antibiotics (including penicillin and cephalosporin) inhibit and or kill bacteria that have
a cell wall, which are critical for the life and survival of bacterial species. Cell walls are built by the
linking of molecules together, Beta-Lactams block this process and without the support of cell wall,
pressure builds up inside the cell and eventually the membrane bursts. Humans and animals don't
have cell walls, we have cell membranes. Some Beta -lactams can attack a cell membrane, instead of
the cell wall and that could be toxic to our bodies and not just the bacteria we are trying to kill off,
these types of antibiotics are used only in clinical setting with supervision of medical staff, such as
colistin.

Antibodies in the Macrolide groups affect ribosomes, which are the cell's protein building machines.
Our cells have ribosomes as well, but there are differences that allow the antibiotics to select
bacterial ribosomes and not human ribosomes, thus safe to take. By preventing ribosomes from
building proteins you effectly kill the cell, since proteins do the majority of the cells work.
Those in the Quinolones group, such as ciprofloxacin and levofloxacin, treat infections like bronchitis
and pneumonia. Quinolones cause the bacteria DNA strands to break when they begin to copy their
DNA for dividing and to be thorough in their jobs, they also prevent the breaks from being repaired.
Without intact DNA even the hardiest of bacteria cannot reproduce.
There are a few other antibiotics that act on selected cellular and metabolic processes that are
essential for the bacterium to live, such as Sulfonamides. Sulfonamides disrupt the bacteria folic
pathways, which are vital to division.
Most antibiotics work against more than one microbe. The antibiotics that affect only a small range
(or types) of bacteria are called narrow spectrum. Some antibiotics are broad spectrum and they
work against many different types of bacteria, including those bacteria that are resistant to narrow
spectrum antibiotics.
The Art of ResistanceBacteria talking to each other
The wide-spread, indiscriminate and improper use of antibiotics around the world
promotesdevelopment of antibiotic resistance. Resistance is a process that microbiologists are still
learning about but they are fairly certain of a few things. Such as, when we over use antibiotics or
use them when we don't need them, viral illnesses for example, resistance can develop. If we do not
take the correct dosage or take as directed, resistance in bacteria can form. Stopping your pills too
early, like most do when they start to feel better, can also cause resistance.
Bacteria are single-celled microbes or organisms whose cell structure is simpler than other
organisms in that there is no nucleus or membrane bound organelles. Instead their control centre
containing their DNA or genetic material is known asa plasmid. It is often in the plasmids that the
genes for resistance to antibiotics are found.
Being a living organism, their primary function is to reproduce and thrive, to thrive, they need to
spread quickly and efficiently. Living things evolve over time, adapt to new surroundings and change
in many ways to make sure of their survival (or their offsprings survival). So, if something like an
antibiotic comes along and inhibits their growth, genetic changes can occur to help the microbe, or
its future offspring to survive the present attack or a future one.
Its only logical that bacteria havethe innate ability to defend itself and this natural innate defence
mechanism (resistance) happens through selective pressure or genetic mutation. It can also happen
by gene transfer, in different ways ways science is only starting to learn about.
Selective pressure occurs when an antibiotic (or anti microbial) agentkills off bacteria not resistant
to it, those that are resistant continue to live and thrive. The antibiotic given will kill the good
bacteria as well as the bad bacteria. When the good bacteria dies off, the resistant bacteria become
the dominant type in the microbial populations.
Mutation occurs during reproduction (or dividing). Most bacteria reproduce by dividing every few
hours, allowing them to evolve and adapt quickly to new environment conditions. During this
replication genes are some times not paired correctly and create a mutation. These mutations can

result in resistance before ever being exposed to the antibiotic.

Gene transfer can happen in a number of different ways vertical gene transfer or horizontal gene
transfer. Vertical gene transfer is basically passing DNA to offspring, where as horizontal gene
transfer is the sharing of genetic material with other organisms. It is the horizontal gene transfer
that worry scientists most.
Generally speaking bacteria species (similar or not) can share information (genes) often through the
plasmids but can also be shared via ribosomes. This information can then be shared with other
microbes or passed along to offspring. The importance of'gene transfer' is that microbes can develop
resistance without ever being exposed to the antibiotic, it needs only meet a bacteria that has been
exposed.
Bacteria can resist antibiotics in a number of ways: by developing the ability to neutralize the
antibiotic before it can harm the bacteria, change the antibiotic attack site so that the antibiotic
can't attach to the bacteria, pump the antimicrobial out of their system before it does damage to the
cell (or wall).
Some bacteria can only becomeresistant to one type of antibiotic, but many more are resistant to
many types of antibiotics, even ones they were not exposed to physically (horizontal gene transfer).
Once antibiotics, of any class, no longer work on the microbe, it is technically incurable and can't be
treated.
In New Zealand, one of the strictest countries in regards to entry and clearing visitors for diseases,
found itself fighting a superbug known as KPC-Oxa 48 a pan resistant organism, it repels every
known kind of antibiotic. In 2013 the man infected died. There was nothing modern medicine could
do for him.[3]
Bacteria that have no known antibiotics, are breast implant problems pictures untreatable or are
starting to become nearly impossible to treat are known as nightmare bacteria. Mid 2013 the
Centers for Disease Control warned that were facing an onslaught of nightmare bacteriaa group of
highly resistant, highly deadly microbes.[4]
Even more disconcerting is the news of a cave in New Mexico, that has not had any human contact
in a time range of four to seven billion years, is full of microbes that are resistant to multiple classes
of antibiotics, including new synthetic drugs[5].
Glaringly exposing just how little we know and understand of microbial processes such as resistance.
The Animation of Antimicrobial ResistanceExplaining all the various mechanisms of transferA Post
Antibiotic EraIt's not pretty
If (when?) we lose our ability to fight off infectious disease with antibiotics due to the problematic
growth of drug resistance, we lose a lot more than just not being able to treat infectious disease.
There would be no surgeries of any kind - heart, lungs, brain, abdomen, none on internal organs
such as bladders, guts or genitals due to those areas being high in microbes (good and bad). We lose
our ability to treat cancer, transplant organs, do any medical procedure that relies on a permanent
port into the blood stream, such as kidney dialysis. There would be no way to implant devices for
hips, knees, elbows or heart valves. Cosmetic surgeries are gone as well, liposuction, plastic surgery
and even tattoos.

We would not be able to treat people after traumatic events such as vehicleaccidents or industrial
mishaps. The safety of modern childbirth will be lost as well, no doubt infant mortality rates would
sky-rocket and deaths by labour would increase as well. Kids would be harder to treat for small
things like falling out of a tree, scraping a knee or breaking a leg.
The food industry would stumble for a few years at least and possibly longer. According to the CDC
eighty percent of all antibiotics go to agricultural animals or their feed. Our cheap food would
become scarce and expensive as stock died off from once non lethal diseases. Eggs, dairy and some
vegetables and fruit would also be affected.
Which Bugs Are Super Bugs And just how super are they
CRE stands for the mouthful, Carbapenem-Resistant Enterobacteriaceae. It's listed by the CDC as
urgent, the strongest level. CRE is a highly contagious and multi resistant bacteria that does not
respond to the majority of antibiotics in use today. The WHO calls it one of the three greatest threats
to human health[6]. CRE pathogens can cause infections in lungs, blood, urinary tract, and other
parts of the body. In at least fourty-eight percent of cases, patients die from the resulting infections.
Some cases are being reported as untreatable.
CDI is known as Clostridium difficile infection. Clostridium difficile (C. Difficile) bacteria are
common bacterium in the environment and in our bodies. But to much of one thing is always bad and
CDI develops, most often, when someone is on antibiotics for a long period of time and the C.
difficile bacteria have taken over the microbiome that is your bowels. When good bacteria are killed
off from antibiotic use, C.difficile can grow and release toxins that can damage the bowel and cause
diarrhea. According to the numbers, CDI kills at least 14,000 people out of the 200,000 it infects in
the USA.[7]
Neisseria gonorrhoeae is a sexually transmitted disease. It'sbeing reported more often that medical
community are finding untreatable cases. Right now one antibiotic still works, but there is not much
agreement on how much longer. Ceftriaxone is the last defence and recently in Japan it was shown
to have high resistance to ceftriaxone. The CDC lists Neisseria gonorrhoeae as urgent. It has been
reported in TEN countries.
MRSA is short hand for Methicillin-resistant Staphylococcus aureus. This is more often than not a
hospital acquired infection (or other health care long-term setting). Though cases are rising of
community acquired infections, which is worrisome to many health care professionals. It can be beat
with any antibiotic other than Methicillin and success rates are higher if you catch it early. To catch
MRSA you have to touch someone infected or something they touched. It is listed as serious by the
Centers for Disease Control and Prevention (CDC).
VRE stands for Vancomycin-Resistant Enterococci. Normally a benign bacteria in your intenstine and
in female reproductive parts. Like MRSA, VRE bugs are resistant to the antibiotic Vancomycin but
success can be found with other antibiotics. The CDC has it listed as serious.
VRSA means Vancomycin-Resistant Staphylococcus aureus, it is causing some worrys with health
care professionals, as staphylococcis aureus bacterium is also resistant to Methicillin. This bug is on
rhinoplasty specialist a close watch list but is listed on CDC threat level as concerning. It is usually
caught at hospitals or long-term care institutions.
Pneumonia There are several strains of the bacteria that cause the most common form of bacterial
pneumonia (pneumococcal pneumonia) tht are becoming resistant to some antibiotics. This is

especially true of penicillins. But it is also true of other types of antibiotics, including
cephalosporins, macrolides, fluoroquinolones, and doxycycline. It takes longer to cure and requires
more hospital assistance.
Tubercluosis (TB) is caused by an organism that is resistant to at the two most potent TB drugs.
These drugs are used to treat all persons with TB disease[8]. Still relatively rare, but growing in
numbers like all superbug cases, is a strain that is not only resistant to the two more potent TB
drugs it's also resistant to fluoroquinolone antibiotic. TB is becoming a real issue for India and
England.
NDM-1is short hand for New Delhi Metallo-beta-lactamase-1. This is not a superbug persay, it is the
creator of superbugs. It is a gene (DNA code) that turns relatively harmless bacteria into 'the most
powerful superbug of superbugs. Any bacteria strain carrying the NDM-1 gene it is resistant to
nearly all known antibiotics, including carbapenem antibiotics - also known as the last resort[9]. This
NDM-1 gene, unlike others, passes quite easily from one strain of bacteria to another and that is
what worries medical professionals the most. NDM-1 is widespread in India and Pakistan, and it has
reached Europe, the USA, Canada and Australia.
Even once easily treatable conditions like urinary tract infections, e-coli infections and salmonella
are becoming increasingly resistant to antibiotics.
New AntibioticsPharmaceutical industry isn't interested
In the beginning of this article I pointed out how quickly microbes were becoming resistant to
antibiotics and that they're losing their effectiveness against bacteria quicker every time they appear
on the market.
The Pharmaceutical industries spend upwards of a billion dollars for every antibiotic they create. It
did not take long for the industry to end research and development for antibiotics, since they were
not making back the money they cost to make. For the last ten years only five antibiotics are in
development.[10] Unlike the hundreds of medications being developed for chronic diseases.
Medications for chronic diseases do not show resistance and they're taken for longer periods of
time. Antibiotics are expensive to make, cheap to sell and are not commonly used for a long time,
there is no money in antibiotics. Pharmaceutical industry is first and foremost a business with a
bottom line. There is no conspiracy here, just simple business math. It does not pay to create
antibiotics.
Some sort of incentive needs to be in place to entice and lure the pharmaceutical companies back
into making antibiotics. I can not fathom any reason they would go back into the antibiotic making
business, unless they were to make a profit or at the very least break even - whether through high
costs of the medicines or government subsidies.
The antibiotic development pipeline is broken; and it is going to take a lot to fix it.
Is There No HopeProtecting yourself and your loved ones too
Health authorities around the world, including WHO, struggle to convince the public of the dangers
antibiotic resistance presents and that it is a crisis and no longer is a what if scenario, but a when
scenario.

There are a few simple things you can do to protect yourself:

The biggest one is washing your hands frequently and keeping your environment clean. Take
antibiotics only when it is appropriate to takeand take it the way you are suppose to for the length
you're told to take it. Educating yourself or at the very least staying up to date with news and
developments. Be aware of your surroundings. particularly in hospitals and old age homes (or other
long-term care facilities).
Bacteria have proven themselves to be resistant and determined life forms, they learn quickly and
stay one step ahead of us it seems. We, humans, have yet to learn our lessons and continually keep
making the same mistakes. Our attitude that antibiotics are a commodity and not a valuable tool in
modern medicine, continues.
But there is hope, we are finding new forms of antibiotics and discovering new ways to attack
infectious disease.[11]Hopefully we will not have to watch the demise of modern medicine and the
entrance of a new post antibiotic era.