SUPERBUGS An intro to bacteria, infectious diseases, and antibiotic resistance.
Infectious Diseases Resistance
-
Upload
ochieng-christopher-odhiambo -
Category
Documents
-
view
4 -
download
2
description
Transcript of Infectious Diseases Resistance
Infectious diseases resistance
During the last decade, the problem of bacterial resistance to
antimicrobial drugs has become a growing concern for the general public
and has been the subject of increased scientific interest. There are fears
that the use of antimicrobials in veterinary medicine and for the needs of
livestock do affects human health in the event of development of resistant
bacteria in animals and transmission to humans by food chain or the
environment. There is still no consensus on the exact responsibility of
antibiotics administered to animals in the development of antimicrobial
resistance and their transfer to human bacteria. The experimental,
epidemiological and molecular data, however, indicate a relationship
between antimicrobial use and the emergence of resistant bacterial strains
in animals, and their spread to humans, particularly through the food chain
[2]. In this report, we intend to look at cases of infectious disease resistance
with emphasis on the balance between research breakthroughs and
resistance rates. Most importantly, we will be answering the question, “Are
bacteria developing resistance too fast for scientists to cope and keep
humans secure from infectious diseases.
Bacteria resistance
Bacteria have the ability to transfer genetic information. Most of these
cases of resistance occur in hospitals. This is an exogenous genetic
information that is retrieved by the bacterium. The first case of resistance
was observed on a Japanese patient. He suffered from a Shigella infection.
The Shigella dysentery caused that could be treated with sulfa, but she had
become resistant to these sulfonamides [1]. The researchers demonstrated
that this resistance was accompanied by in vitro resistance to other
antibacterial. They isolated in the digestive tract of other sick, the strains of
Escherichia coli that had developed resistance to sulfonamides by horizontal
transfer between the two species [2, 6].
There are resistance Inherent microorganisms with respect to some
infectious agents. This is verified when there insensitivity of all strains of a
species or a bacterial genus facing one (or more) kind (s) of antibiotic (s). It
depends on the cell constitution of a microbe that allows it to escape from
the mechanism of action of a particular antibiotic. So this is actually an
"insensitive" natural, not acquired resistance, although in both cases the
result looks the same during a possible treatment [3]. The "resistance" is
not the natural result of an evolution of the species since the advent of
antibiotics. It is not this type of resistance that causes the problem since
other cell components may be targeted by other classes of antibiotics
against these strains.
A strain resistant when expressed is capable of supporting a much
higher concentration of antibiotic that inhibits the growth of most other
strains of the same species. In cases of acquired resistance, initially, the
strain was not resisting, but over time, there has been a change in this
population [4, 6]. This type of resistance is related to a process of natural
selection. Imagine a population of bacteria that is regularly bombarded with
antibiotics. Most bacteria will die, unable to withstand the attack of
antibiotics. By cons, some bacteria will resist, with some mechanisms
described below, and survive. As the reproduction of bacteria is very fast,
are those that are resistant, in reproducing, transmitting the resistance to
their descendants. The bacteria population will become stronger as more
and more people wear resistance gene relative to those who do not. It
should not be confused with a quick snapshot [3]. Acquired resistance does
not happen overnight. But if one compares the time it takes for bacteria to
become resistant and the time that humans take, it's very fast. This is due to
very short generation time for bacteria (less than 20 minutes in many cases)
as compared to humans.
Evolution of resistance
By 1945, penicillin G was used to counteract the staphylococcal
infections. In 1947, we already spotted the first resistant strains of
staphylococci. The latter produced an enzyme capable of degrading
penicillin. In 1957, three families of antibiotics were on the market and
staphylococci had developed resistance to them all [7]. In 1997, some
strains were resistant to one or other of the seven classes of antibiotics
once effective. In the 40s, another bacterium, Neisseria meningitidis,
already showed the resistance to sulfonamides, a family of antibiotics.
Bacteria take about 2 to 4 years to develop the resistance to new
antibiotics. They can develop new mechanisms and escape their attack.
In 1980 appeared the phenomenon of multi-resistance. A
microorganism can become multidrug-resistant when contacted with
several antibiotics. Needle, thread, the bacterium is resistant to one, then
two antibiotics. Finally, she finds herself in a different environment where it
is exposed to other antibiotics [3]. The bacteria may resist already at some
of these new products (if they attack, for example, the same cellular targets
as their predecessors) and can demonstrate additional resistances. Now
found bacteria that are insensitive to more than 10 different antibiotics.
These agencies include Streptococcus pneumonia, Staphylococcus aureus,
Mycobacterium tuberculosis, Salmonella sp., Campylobacter sp. and
Escherichia coli [4]. There is often multi-resistant bacteria in hospitals. It is
estimated that multi-resistant bacteria in hospitals are responsible for over
two million and a half of infections and thousands of deaths each year in
North America.
Mechanisms of resistance
In order to counteract the action of antibiotics, bacteria use several
types of mechanisms, which are more and more known by researchers. In
the picture that follows, four of these mechanisms are discussed.
Interference: produce enzymes capable of inactivating
antibiotics
This mechanism is based on the destruction of an antibiotic even
before it enters the cell. Occurs via secretion by the bacteria an enzyme
capable of destroying chemical bonds necessary for the functional integrity
of the drug. It is therefore an offensive strategy by which bacteria the
antibiotic inactive [8]. Beta-lactamases are an example of enzymes
produced by bacteria that inactivate B-lactam antibiotics such as penicillin
and cephalosporin. Other classes of enzymes specifically inactivate
aminoglycosides or other antibiotics, including chloramphenicol and
fosfomycin.
Shielding and efflux: get impervious to penetration of the
antibiotic or reject
It is evident that the outer membrane of Gram-negative bacteria
contain porins, kinds of proteins that form channels for the passage of
several types of molecules, which also benefits penicillin. The resistance
mechanism called "shield" is therefore to modify the bacterium to the
number of porins and / or specificity thereof [7, 8]. For example, if the
number of porins decreases, the antibiotic will be more difficult to enter the
cell. If porins become impermeable to certain substances, this will have the
effect of reducing the intracellular penetration. It is a specific resistance
mechanism to gram-negative bacteria that do not affect Gram-positive
bacteria, since in the latter the antibiotic can flow freely through the cell
wall and cytoplasmic membrane [4].
If it appears that the antibiotic penetrates a cell, it is also a
mechanism that causes the bacterium to reject it outside, preventing it from
reaching its target. The concentration of antibiotic is still insufficient to be
toxic [6, 8]. This is called "active efflux" mechanism. The bacterium
manages this feat by using molecular pumps. Tetracycline is an example of
antibiotic countered in this way.
Camouflage: change the structure of target cells antibiotics
It should be understood that an antibiotic will not attack anything on
bacteria. To be effective, an antibiotic must bind to a target cell. If the
bacteria replaces or amends this target, the action of the antibiotic will be
reduced since it will no longer settle there. This type of resistance is found
among others against macrolides (e.g. Erythromycin) [4].
Dodge or evasive strategy
In this situation, the antibiotic reaches its target. However, the
bacterium is able to use other metabolic pathways for the same work.
Activities inhibited by the antibiotic are replaced. Bacteria use this strategy
against sulfonamides and glycopeptides [6, 8].
Transfer of resistance genes
High above described resistance mechanisms are sometimes
attributable to the existence of genes which either produce enzymes
capable of degrading the antibiotic or are responsible for intracellular
changes making inoperative the antibiotics. These resistance genes can be
carried on the main chromosome of the bacterium or genetic entities called
plasmids, transposons or integrate [3]. They have, in all cases, the ability to
be transmitted between bacteria which consequently acquire the element
responsible for their new state of resistance to a particular antibiotic. This
transfer of resistance genes is not only because of the very rapid
reproduction of bacteria (so-called vertical transfer within the same strain),
but it is mainly based on three horizontal axes called transformation,
transduction and conjugation [2, 7]. This horizontal transfer of resistance
genes from one bacterium to another or from one species to another, allows
extremely rapid dissemination of genetic information.
Transformation:
The transformation allows the acquisition and integration of naked
DNA. This "free" DNA may be from a bacterium, for example dead. The
naked DNA is outside of the bacterium and is then picked up by the latter
[7]. Once detected, the DNA is incorporated into the DNA of the bacterium
and will be subsequently transmitted. If resistance genes were present in
the naked DNA, these genes can also be transmitted. This mechanism is not
widespread but it allows a genetic exchange between bacteria that are very
different.
Transduction:
Transduction, the vector (or genetic element that allows to insert a
DNA fragment into a host cell) is a bacteriophage (bacterial virus). In
replicating the virus integrates its DNA to that of the bacteria [7]. When
leaving the bacterium, it carries with it the DNA sometimes containing a
few resistance genes. The following figure is an example of transduction. As
the bacteriophage attack many bacteria, it will transmit the resistance
genes to other bacteria. Transduction is efficient only for strains of bacteria
very similar.
Conjugation:
Conjugation is a process whereby DNA is transferred from a donor
cell to a recipient cell by simple contact of the cell membrane [3, 7]. The
chromosome of the host bacterium blue in the resistance gene. Then,
another bacterium just join the first. Upon contact, there is a transfer of the
resistance gene [8]. Following this interaction, both bacteria possess the
resistance gene. This mechanism is the most common and is primarily
responsible for horizontal transfer.
Impact of bacteria resistance in the medical field
At present, antibiotics are the second most commonly prescribed
drugs in world, behind those prescribed for heart disease. Here we see one
of the main causes of the problem of resistance to antibiotics overuse [7].
Antibiotics were prescribed too. Doctors often prescribe antibiotics to
satisfy a patient. However, too many patients have used these drugs
unnecessarily. A study was made on the requirements of the trends toward
preschool children in Canada. It was found that 51% of prescriptions (the
number of 66 419) were not necessary. It is easy to think that if the doctor
is not quite sure of his diagnosis and the patient lobbied for medication, the
doctor may prescribe an antibiotic hoping that it is a bacterial infection and
not viral. However, we must remember that antibiotics are ineffective
against viral infections (such as flu). This is one of the causes of antibiotic
resistance [3, 8]. This problem must be resolved. Doctors should make clear
to patients that antibiotics do not cure everything. It will be a tough task to
make this clear to everyone. And doctors should stop succumbing to the
pressures of patients who want to have a "pill to cure."
Moreover, some infections cause increasingly of concern among
physicians. We are talking about ear infections and septicemia caused by
Streptococcus pneumoniae urinary tract infections caused by Escherichia
coli, collective food poisoning caused by Salmonella typhimurium and
tuberculosis (Mycobacterium tuberculosis) [4, 7]. Therefore, the risk of not
prescribing an antibiotic when it is actually required puts extra pressure on
the doctor whose social responsibility is great. So we see the urgency to
develop rapid diagnostic tests can confirm in less than one hour rather than
two days, if there is a bacterial or viral infection and that will identify
precisely infectious agent and simultaneously detecting the presence of
genes for resistance against a particular antibiotic [6]. such tests based on
molecular biology techniques (genetic) are under development in research
laboratories, some are even available on the market (against the Group B
Streptococcus in the newborn born and staphylococcus aureus against
methicillin-resistant) and they will better treat infections and to effectively
control the judicious use of antibiotics (MG Bergeron, New England Journal
of Medicine) [7].
Conclusion
Fatal bacterial diseases such as tuberculosis, pneumonia, diphtheria,
syphilis, tetanus or against which there was no cure 60 years ago can now
be treated with antibiotics. Today it is considered that their therapeutic use
has allowed to extend the average duration of human life of ten years.
However, there was an increase in all of the antibiotic resistance of the
bacteria, i.e. their ability to resist antibiotics. The fight against antibiotic
resistance happens of course the search for new antibiotics, but it begins
mainly by a more reasoned use of antibiotics available, the risk to be in ten
or twenty years too poor at the beginning of the twentieth century against
the Infectious diseases.
References
[1]. A.-P. Magiorakos , A. Srinivasan, R. B. Carey, Y. Carmeli, M. E.
Falagas, C. G. Giske, S. Harbarth, J. F. Hinndler et al. Multidrug-
resistant, extensively drug-resistant and pandrug-resistant bacteria....
Clinical Microbiology and Infection, Vol 8, Iss. 3 first published 27 July
2011 [via Wiley Online Library]. Retrieved 16 August 2014.
[2]. Benson, M. A., Ohneck, E. A., Ryan, C., Alonzo, F., Smith, H.,
Narechania, A., & Torres, V. J. (2014). Evolution of hypervirulence by
a MRSA clone through acquisition of a transposable element.
Molecular microbiology, 93(4), 664-681.
[3]. Boucher, HW, Talbot GH, Bradley JS, Edwards JE, Gilvert D, Rice LB,
Schedul M., Spellberg B., Bartlett J. "Bad buds, no drugs: no ESKAPE!
An update from the Infectious Diseases Society of America". Clinical
Infectious Diseases. 2009 Jan 1;48(1):1-12.
[4]. Fauci AS (2005). "Emerging and reemerging infectious diseases: the
perpetual challenge". Academic Medicine 80 (12): 1079–85.
[5]. Krishnapillai, V. (1996). Horizontal gene transfer. Journal of Genetics,
75(2), 219-232.
[6]. Taylor, L. et al. (2001). Risk factors for human disease emergence
Philosophical Transactions of the Royal Society B, 356(1411):983-9.
[7]. Witte, W (1997). "Increasing incidence and widespread dissemination
of methicillin‐resistant Staphylococcus aureus (MRSA) in hospitals in
central Europe, with special reference to German hospitals.” Clinical
Microbiology and Infection 3 (4): 414–22.
[8]. Witte, W., Kresken, M., Braulke, C., & Cuny, C. (1997). Increasing
incidence and widespread dissemination of methicillin‐resistant
Staphylococcus aureus (MRSA) in hospitals in central Europe, with
special reference to German hospitals. Clinical Microbiology and
Infection, 3(4), 414-422.