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

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