How do Bacteria Like MRSA Develop and Spread Multiple Antibiotic Resistance?

How do Bacteria Like MRSA Develop and Spread Multiple Antibiotic Resistance? Sex plays an important role in the spread of bugs resistant to multiple antibiotics. Bacteria have jumping genes (also called plasmids or transposons) which cut themselves out of their chromosomes and are transmitted to other organisms during sex. This report explains how this happens and what we should do to minimise the risk. 

MRSA an Antibiotic Resistant Gram Positive Bacteria
MRSA an Antibiotic Resistant Gram Positive Bacteria (Staphylococcus)

While you read why not listen to my album ‘Electro Baroque‘ (all tracks are also available on iTunes using the link here)? Classical music using modern instruments:

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Most of us are aware of the recent development of killer bugs that have become resistant to many of the antibiotics used against infectious diseases. Our hospitals are favoured breading grounds for these ‘super’ bacteria causing them to thrive in the very places we visit to get treatment against them. Few people however understand how these unpleasant killers become resistant to our drugs. Where does the resistance come from and how can it spread between bacteria? Why do super bugs flourish in hospitals?

Over 40 years ago in 1974 Alan Jacob and Susan Hobbs published research demonstrating that jumping genes are transmitted between bacteria when they engage in sexual activity. Specifically they demonstrated this phenomenon in streptococci bacteria which normally live in the human gut. They belong to a broader group of microbes known as gram positive bacteria – this group causes many of the most unpleasant human diseases. Like humans bacteria store all of their genetic information in chromosomes. Jumping genes can jump out of the chromosome of one bacteria and then transfer into another bacteria as they engage in sex. These jumping genes can then insert themselves into the chromosome of their new host.

Streptococcus (now called Enterococcus) faecalis
Streptococcus (now called Enterococcus) faecalis

At this stage I have to declare a personal relationship with one of the discoverers of antibiotic resistant jumping genes. Less than 5 years after Jacob and Hobbs published their seminal paper I was fortunate enough to carry out a research project under the supervision of Dr. Alan Jacob as part of my first degree dissertation in the Bacteriology Department based in Manchester University’s Medical School. My own research used the same bacterial strains featured in Jacob and Hobb’s original work and I spent the best part of a year trying to better understand this phenomenon of bacterial sex and how it gets hijacked by jumping genes to create the killer bugs that are the scourge of modern hospitals.

So what are these jumping genes? In the scientific community they are normally referred to as plasmids or more recently transposons. In my last article explaining how turning off genes can lead to depression I described a simple way to visualise genes strung along a chromosome like a set of beads on a necklace (the link to my ‘depression’ article is here). Bacteria generally have one very large circular chromosome (‘necklace’) containing all of their genes (the ‘beads’). Each gene contains the construction information for a key piece of equipment needed by a fully functioning bacteria (most of this equipment is in the form of proteins – which are miniature pieces of molecular machinery).

Bacterial Plasmids
Bacterial Chromosome (DNA) and Plasmids (also DNA which may include antibiotic resistance genes)

Sometimes bacteria possess genes along a short section of their DNA ‘necklace’ which can cut themselves out of the big chromosome and create a mini necklace – a plasmid (see the diagram above). These genes, that are able to extract themselves out of the main chromosome (necklace), are what we sometimes refer to as jumping genes. They can literally ‘jump’ out of a chromosome and at a later stage re-insert themselves back into the chromosome (or into the chromosome of another bacterium following sex).

Plasmids, with their short strand of genes, can exist either within the much bigger chromosome or they can exist separately from it as a free circle of genetic material floating within the bacterial cell. Although a typical plasmid does not contain as many genes as a whole bacterial chromosome it can carry some very useful genes. For example a plasmid may carry genes which help a bacteria to resist being killed by antibiotics. It was this kind of plasmid that I investigated nearly 40 years ago. It carried resistance to the antibiotics streptomycin, kamaycin, neomycin, erythromycin and tetracycline.

Pili on the surface of Streptococci
Pili (hairs) on the surface of ‘male’ Streptococci

When it comes to survival bacteria can be very versatile. As with higher forms of life they use sexual activities to share useful bits of genetic information with each other. Often bacteria containing plasmids will have small appendages like hairs or tubes on their surface – we can think of these as the ‘male’ bacteria. The photo above is of these appendages or pili on the surface of the streptococcus I worked on in 1979 (sorry about the quality but these electron microscope pics were taken 37 years ago!).

If a hairy male bacterium (containing a plasmid) comes across a ‘female’ bacterium that does not have these pili on its surface they ‘get together’. One of the things I found in my research was the existence of a sex hormone or pheromone given off by the ‘female’ bacteria to entice the ‘males’ into conjugative behaviour. If the conditions are right the ‘male’ will then transfer a copy of his plasmid into the ‘female’ bacterium. In this way any genes on the plasmid such as those for antibiotic resistance can be spread through the local bacterial community (bacteria are not strictly speaking male and female but this analogy should help you to understand what is going on).

Bacterial 'sex' (Conjugation) used to transfer plasmids (jumping genes) with antibiotic resistance
Bacterial ‘sex’ (Conjugation) used to transfer plasmids (jumping genes) with antibiotic resistance

OK – this explains somewhat simplistically how bacterial sex works in spreading multiple antibiotic resistance but where did this resistance come from in the first place? To understand this we need to appreciate where most antibiotics exist in nature. Scientists in pharmaceutical companies spend a lot of time messing about with soil. This is because in soil there are huge numbers of different kinds of bacteria and other microbes all living together. This is not however a very peaceful co-existence – the bugs are highly competitive and constantly fire selective killer chemicals into the soil around them to kill off their neighbours. After killing off the competition they can eat their share of the nutrients (in fact they will also eat their dead neighbours).

Pharmaceutical scientists try to find and evaluate these selective killer chemicals produced by microbes. They hope to find ones that can kill disease causing bacteria but will not harm humans. This is how many antibiotics were originally discovered. Some, like penicillin, were simply products made by microbes that very effectively killed other microbes. Others were chemical modifications of microbial products which were more effective or more selective in killing their target organisms.

Antibiotics killing Gram Positive Bacteria growing on a plate of agar jelly
Antibiotic ‘dots’ killing Gram Positive Bacteria growing on a plate of agar jelly

I produced an article about 4 years ago explaining how bugs living in the soil had also developed defence mechanisms to protect themselves from killer chemicals produced by their neighbours (the link to my soil bacteria article is here). Scientists had discovered that the genes for these antibiotic ‘defence’ mechanisms could be transferred between bugs by – yes you guessed it – bacterial sex. Their results showed that antibiotic resistance found in bugs in hospitals was the same as that found in soil bugs. This meant that hospital bugs may be picking up antibiotic resistance by sex with soil bugs.

In the hospitals we have historically used our armoury of powerful antibiotics in a very uncontrolled and uncoordinated manner. Rather than testing each patient to check which microbial strain causes their disease and then identifying precisely which antibiotic kills that strain they have tended to use antibiotics on a try-it-and-see basis. Here they use the patient as a test laboratory – if the first antibiotic doesn’t work then they try another, and perhaps another until symptoms improve.

Antibiotics don't work on viruses like flu or cold bugs
Antibiotics don’t work on viruses like flu or cold bugs

In addition to wasting patient time and hospital resources each time an antibiotic is unsuccessfully used it increases the concentration of bugs resistance to that antibiotic. The hospitals are using patients as incubation chambers to select and concentrate antibiotic resistant bacteria. About 90% of the cells in our bodies are not human cells – they are bacterial cells that normally live in harmony with us in our guts and on our skin. Some of these bacteria will be naturally resistant to certain antibacterial agents and through microbial sex with jumping genes they spread the resistance to their neighbours. If we kill all the antibiotic sensitive bugs through uncontrolled antibiotic use the few resistant ones left will have a field day enjoying all the nutrients left behind. Before long most of the bacteria in our bodies will be the drug resistant ones.

Bacterial Cell
Bacterial Cell – 90% of the cells in our bodies are microbes which live in harmony with us.

Not only are we concentrating antibiotic resistant strains in our hospitals but since we also feed a lot of our farm animals with antibiotics we are also developing antibiotic resistance centres around our farms. Any bugs that happen to get washed out of the farm or hospital into the local soil (perhaps via the sewage) will then be able to transfer their resistance genes through sex with other bacteria in the soil. And so the vicious circle continues – mankind has taken some incredibly useful antibiotic products and effectively made them useless by uncontrolled excessive use in hospitals and by feeding them to farm animals.

The pace of increase in our knowledge about molecular biology is phenomenal and we are already finding that this knowledge is helping us in the fight against terrible diseases like cancer. We should however learn from history – it is over 40 years since jumping genes and bacterial sex were identified as important factors in the spread of multiple antibiotic resistance in hospitals. My own dissertation was written in 1979. Today many of the pathogens identified in our hospitals are resistant to the main drugs we have developed to use against them.

Chris Duggleby 1979 Jumping Genes Dissertation
Chris Duggleby 1979 Jumping Genes Dissertation

The advance of multiple antibiotic resistance could have been slowed by:

  • testing the sensitivity of pathogens isolated from a patient before using drugs – only use antibiotics that work on that pathogen to keep drug usage to a minimum.
  • using antibiotics in controlled campaigns – rotating their use instead of using them all at the same time – as soon as the prevalent bugs develop resistance to the current drug you can rotate to a new drug and stop using the first one (until resistance levels in the local bacterial population subsides).
  • banning the use of antibiotics similar to those used in human medicine for animal farming purposes.

To see an illustrative video of bacterial sex (parental guidance not necessary) here is a link.

When I prepared the Duggleby family tree going back nearly 1000 years I was struck by how many families were nearly wiped out by diseases like small pox, diphtheria and plague (Link to the tree is here see pages 9, 10, 29, 32, 46, 78, 110 – look for the black boxes). Sadly as we come close to conquering the worst effects of some forms of cancer we may be faced with the return of some of these old diseases due to our inability to apply antibiotics responsibly. Of course we could provide drug companies with financial incentives to develop new antibiotics – welcoming in an era in which new antibiotics will be as expensive as the treatments for leukaemia or AIDS.

Chris Duggleby

Chris Duggleby 1979 outside Manchester Medical School
Chris Duggleby 1979 outside Manchester Medical School
Chris Duggleby 1979 Dissertation Summary
Chris Duggleby 1979 Dissertation Summary (from the days when typewriters ruled the Earth!)

Here is a link to the original paper in which Alan Jacob and Susan Hobbs first identified multiple antibiotic resistance plasmid transfer via conjugation in gram positive bacteria (‘jumping genes’). The importance of their work was recently (2016) reconfirmed in an editorial in the Journal of Bacteriology – link here.Penicillin see article on jumping genes and bacterial sex at chrisdugglebydotcom

If you found this article interesting please consider taking a look at some of his other recent reports on similar subjects.

Just click on the titles below:

…starting with some more serious stuff:

28th Feb 2017: Vaccinations Cause Children to Masturbate, as well as Dyslexia, Autism, Sleep Disorders and Brain Tumours

31st May 2016 Linking Poverty to Depression – Genes of Poorer Adolescent Children Permanently Labelled for Depressive Behaviour

21st May 2016 Skin Cancer and Cataracts From Your Car – Poor UV Side Protection – Windows Tested From 15 Vehicle Makers

19th April 2016 Torture In The Shower – Face and Body Soap AllergiesMain Suspect: Pears Transparent Soap

14th March 2016 Eliminating Noisy Commuter Calls – Cheap Cell Phone Jammers – Hidden Costs:

13th March 2016 Bugs Evolve That Can Eat PET Plastics Used In Bottles And Textiles

3rd March 2016 Using Gene Drives To Change Mosquito Sex In Fight Against Zika, Dengue and Malaria

1st March 2016 Ladies – upto half a satisfying sexual event per month but risk of side effects from “Pink Viagra” Flibanserin (“Addyi”)

14th Feb 2016 Breast CancerHow Blind People Use Their Enhanced Tactile Sensitivity to Save the Lives Of Women With Tumours

3rd Feb 2016 Zika Infection Spread By Sex In Dallas – Earlier Sexual Transmission In Colorado – Detailed Symptoms 

1st Feb 2016 Sexual Competition Between Women – Ovulation Can Be Seen In The Face

31st Jan 2016  Bed Bugs – Insecticide Resistance – Arbovirus Transmission – Zika and Microcephy

19th Jan 2016 ZIKA Virus Epidemic  – Health Warning – Pregnant women should postpone travel to affected areas – Including Brazil 

17th Jan 2016 Bubonic Plague Special – Lice – Hosts for The Black Death Bug

13th Jan 2016 Kill Head Lice In A Day With The Newly Developed Plasma Nitcomb From The German Fraunhofer Institute

8th Jan 2016 Cancer from Handbags, Shoes and Gloves – Allergic Reactions to Jewellery – German Institute Identifies Excessive Chromium 6 and Nickel Levels

26th July 2015 Poison in your Washing Machine: Allergic Contact Dermatitis from Laundry Detergents, Softeners, Conditioners and Whiteners

17th October 2015: Health Risk: Vitamin and antioxidant supplements help cancer cells become malignant – latest research from Texas

31st May 2015: German Concern about Potentially Carcinogenic Aromatic Hydrocarbons in Cosmetics  

29th December 2012: Spreading diarrhea and vomit through the washing machine– The Norovirus propagator in our kitchen

and here are some fun related articles:

19th March 2016: JoggersHow To Stop Dogs Chasing You – Research Into New Pet Friendly Technology

9th March 2016: Penis Ring Emergency – German Fire Fighters Rescue Man From Painful 13 Cock Ring Torture: Vorsprung durch Technik and erectile dysfunction

4th March 2016: Dachau Industry Park Evolves From Concentration Camp To Nudist Wellness Club (Brothel)

21st June 2015: Bio-undies: Guilt free Passion with ‘Easy Emma’ and ‘Loose Harry’and Getting Rid of Garden Snails with Rent-a-Duck

4th March 2015: Hamburg Reeperbahn (St. Pauli): Germans install walls that urinate on passers-by

17th April 2014: Niche On-line Dating Services (Specialities: Herpes, Thrush and Genital Warts)

18th March 2014: Germany and Finland Joint Investigation: New Case of Sexual Cannibalism Including Self-mutilation (Castration) During Intercourse.

18th August 2012: How Bavarians and Austrians use their middle finger – Fingerhakeln: a men-only sport (did Arnold Schwarzenegger start training this way?).

You can also find some of my more humorous reports in the Alpine Press section of this site using the link here.

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