Download Antibiotic resistant bacteria Karl Ochs

Antibiotic resistant bacteria
Karl Ochs
Introduction
History of Antibiotics
Antibiotics have been in use for many years in treatment of infections. It was until
the last century that people knew the infections that are caused by bacteria. The ancient
Egyptians used various plant extracts and moulds to treat infections. In the 20th century, it
was realized that some infections such as diarrhea and pneumonia were caused by bacteria
and they were the leading cause of death in developed countries (1).
Paul Ehrlich, a German physician in the 19th century some bacterial cells were
colored unlike others. This made him come to a conclusion that some bacterial cells could
be killed selectively without other cells being harmed. Arsphenamine was found in 1909 to
be effective in treatment of Syphilis. This was referred to be the first modern antibiotic
even though it was called chemotherapy during that time.30 years, Selman Waksman
discovered more than 20 antibiotics.
In 1928, Alexander Fleming discovered penicillin accidentally as Penicillium
notatum had created bacteria free zones on a plate. It was isolated and grown in pure
culture. Mass production of penicillin was done. There was a huge fire in Boston in the
United States and many people died due to infection by Staphylococcus. Penicillin was used
successfully in the treatment of this. In 1945, Alexander Fleming, Howard Florey and
Ernest Chain were awarded for mass production of antibiotics.
Introduction to resistance
This is the ability of a bacteria to resist medication previously used against them.
Resistance occurs due to one of three reasons that is random mutations, misuse of
antimicrobial agents and genetic mutations. Those microbes that are resistant to many
antimicrobials are referred to as multidrug resistant. Many infections are not treatable
today because of resistance. Resistance can be attributed to high use of antibacterial in the
human population and animals and an increased resistant strains in both human and nonhuman sources (2).
Thesis statement
Infectious diseases have challenged humanity since time immemorial. We have
however developed antibiotics to do away with the infections that have challenged us since
our existence. Since the introduction of Penicillin as the first antibiotic, other antibiotics
have been developed to counter even bacterial infections. Despite this achievement, as
humans have evolved in their ways of fighting bacteria, the bacteria itself has been evolving
during this period. There is a growing number of resistant bacteria today. In this paper, I
will examine the difference between gram positive and gram negative bacteria, the
mechanisms of action of some bacteria and the types of resistant bacteria in place today.
Types of bacteria
Eukaryotes vs Prokaryotes
Cell walls
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The cell wall of prokaryotic cells if present contains peptidoglycan or mucopeptide
while in eukaryotic cell, if the cell wall is present then it contains cellulose and
peptidoglycan is absent
Peptidoglycan
This is part of prokaryotic cell wall that forms a mesh like layer outside the plasma
membrane. It has alternating residues of N-acetylmuramic acid and N acetylglucosamine. A
peptide chain of there to five amino acids is attached to N-acetylglucosamine.
(Source: 4)
A peptidoglycan layer is formed by two alternating amino sugars NAM and NAG
which are joined by a glycosidic bond. Both of the amino sugars have L-alanine,
mesodiaminopimelic acid, D-glutamine and L-lysine but in different compositions. The
cross linking of these amino acids is carried out by the enzyme DD transpeptidases (3).
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Gram positive vs gram negative prokaryotes
What’s the difference, thickness and surroundings.
Gram positive prokaryotes do not have an outer membrane. Their cell wall is 2030nm thick and they contain 70-80% murein. The cell wall is smooth and has teichoic
acids. The lipid content is very low and the cell wall does not have porins.
In gram negative prokaryotes, the outer membrane is present. The cell wall is wavy
and comes into contact with the plasma membrane in a few loci. The cell wall is 8-12nm
thick. Lipid content in the cell wall is about 20-30%.In the outer membrane, hydrophilic
channels or porins occur. Teichoic acids are however absent unlike in gram positive
prokaryotes
Other minor differences between the two include that the basal body of the
flagellum in gram positive prokaryotes cell wall contain two rings and that mesosomes are
quite prominent. In gram negative prokaryotes, the basal body of the flagellum has four
rings and mesosomes are not as prominent as in gram positive prokaryotes
(Source: 4).
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How to test, how it works
Differences between gram positive and gram negative prokaryotes can be tested by
use of gram staining. The test is based on differences in cell wall constituents between the
two groups of prokaryotes. The gram stain procedure distinguishes between gram positive
and negative by formation of either red or violet color. The thick layer of peptidoglycan in
gram positive bacteria make them to stain violet. In gram negative prokaryotes, the
peptidoglycan wall is thinner and they therefore stain red (5).
Gram staining involves three main processes. In the first stage, staining with a water
soluble dye known as crystal violet is done followed by crystal violet and then
counterstaining. Cells are stained with crystal violet and iodine solution is added leading to
a complex formation which is insoluble in water. A decolorizer such as acetone is added to
dehydrate the peptidoglycan layer. The crystal violet and iodine complex are not able to
pass through the peptidoglycan layer. In gram negative prokaryotes, the outer membrane
is degraded and the peptidoglycan will retain the crystal violet-iodine complex. During the
counterstain step, a water soluble safrarin is added to the sample to be tested and it stains
it red. Safrarin is lighter than crystal violet but is does not however affect the purple
coloration in gram positive bacteria cells. In gram negative bacteria, the cells are stained
red.
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How antibiotics work
What antibiotics do
There are similarities and differences between the human and bacteria cells.
Antibiotics work by disrupting processes in bacterial cells only. Since human cells do not
have cell walls unlike bacteria, antibiotics like penicillin will work by keeping the bacteria
from building a cell well. The formation of peptidoglycan layer, a component of cell wall is
inhibited. Human cells and bacteria also differ in their cell membranes and machinery they
use in the replication of DNA. It has been found that some antibiotics dissolve bacterial cells
membrane while others affect DNA copying machinery or protein building which is specific
to bacterial cells.
Different classes
Beta-Lactams. Penicillins and Cephalosporins.
Their mode of action is mainly inhibition of cell wall synthesis. They are
characterized by a four membered beta lactam that is at the center of the structure. This
class of antibiotics also target penicillin binding proteins which are groups of enzymes
found in the cell membrane. The enzymes are involved in formation of cross links with the
bacterial cell wall. The Penicillin binding proteins have been found to be bound to the betalactam ring and therefore they do not perform their functions in cell wall synthesis.
Eventually, this lead to bacterial cell death because of autolysis or osmotic instability
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Macrolides.
They are also referred to as protein synthesis inhibitors. The main mechanism of
action is inhibition of protein biosynthesis in bacteria. This inhibition has been known to be
caused by prevention of peptidyltransferase from adding a peptide group attached to a
transferRNA in the adjacent amino acid. It has been also suggested that another mechanism
of action of this class of antibiotics is that they cause premature dissociation of peptidyl
transfer RNA from the ribosome. Their action is considered to be bacteriostatic as they
reversibly bind to the P site of the 50S subunit of the bacterial ribosome.
Fluoroquinolones.
Together with quinolones, this class of drugs inhibit bacterial replication by
affecting the DNA replication pathway of bacterial cells. DNA houses the genetic materials
of bacterial cells and it is indeed necessary for the normal functioning of a cell. Double
stranded DNA unwinds during the process of replication and this allows complementary
base pairing to take place. DNA unwinding is done by enzymes DNA Topoisomerase and
DNA gyrase. DNA gyrase is a Topoisomerase II enzyme that leads to unwinding of DNA by
causing negative supercoils and also cause relaxation of positive supercoils.
Fluoroquinolones therefore inhibit this enzyme through binding to A-subunit. This means
that bacterial cells would not be able to replicate and carry out protein synthesis.
Tetracyclines.
The main mechanism of action of Tetracyclines is that they inhibit proteins
synthesis in bacterial cells by preventing the attachment aminoacyl transfer RNA to an area
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of the ribosome called A site. Binding occurs in the 30S subunit of bacterial ribosomes.
Through this process, introduction of amino acids to the nascent peptide chain are
prevented. Upon withdrawal of the drug, this action can however be reversible (Anon).
Aminoglycosides.
This class of drugs exhibit a concentration dependent activity against gram negative
bacteria. Their mechanism of action is also inhibition of protein synthesis. They disturb
peptide elongation at the 30S ribosomal subunit of bacterial cells. This gives rise to
inaccurate translation of messenger RNA therefore the biosynthesis of proteins in bacterial
cells is stopped. Subsets of aberrant proteins that were incorporated into the cell
membrane of bacteria could affect its permeability (6).
How resistance is gained in bacteria
Evolution theory
Basic evolution theories
With the introduction of new antibiotics, development of resistance has been
inevitable. Antibiotic resistance in any given bacteria may be related to the traits of the
organism for example cell wall characteristics that make it to be naturally resistant .In
acquired resistance, it results from mutations in its DNA and resistance conferring DNA
from another organism may be acquired.
According to the gene transfer theory, spontaneous antibiotic resistance frequency
increases. Although the process of mutation is very rare, it doesn’t take a long time before
resistance to a particular resistance is developed in a population. In vertical evolution,
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resistance genes are transferred to the bacteria`s progeny directly during the process of
DNA replication
According to the horizontal gene transfer theory, genetic material are housed in
small section of DNA that can be passed between the individual bacteria with the same or
different species. Transduction, transformation or conjugation processes are associated
with horizontal gene transfer.
Examples of bacteria gaining resistance
Penicillin, penicillinase example
Resistance has developed for some antibiotics that were used in treatment of
bacterial infections in the past. Examples of this include Neisseria gonorrhoeae and
Staphylococcus aureus which have now become resistant to benzyl penicillin. However, the
infections caused by these bacteria in the past have been treated by this antibiotic (7).
Some bacteria have become resistant to even the most accessible antibiotics. This is
a major public health problem since these bacteria are in a position to cause life
threatening infections. They include Staphylococcus aureus which is resistant to methicillin
antibiotic while Enterococcus is resistant to Vancomycin. Mycobacterium tuberculosis
bacteria is resistant to many antibiotics including penicillin.
The growing concern of antibiotic resistant bacteria
According to the World Health Organization, antibiotic resistance has been a global
public health threat that requires immediate action across all governments. Klebsiella
pneumonia bacteria has developed resistance for many drugs. Carbapenems have been
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reported to be effective to this bacteria in some countries. For E.coli the use of
Fluoroquinolones and quinolones has been ineffective in some countries (7).
Example of past examples of poor handling of situation
The emergence and spread of antibiotic resistance has been accelerated by genetic
changes. Abuse and misuse of antibiotics has also contributed to this emergence. Examples
where poor handling of situation has occurred is where people with viral infections like flu
are given growth promoters found in fish and other animals. Antimicrobial resistant
bacteria are found in animals, food and the environment that we live in. Poor infection
control and improper handling of food have also contribute to antimicrobial resistance (8).
Example of some steps taken
According to the Centre for Disease Control and Prevention, patients and healthcare
providers must work with policy makers in ensuring that effective strategies are put in
place for ensuring that resistance to antibiotics is reduced. Patients should take antibiotics
as directed by physicians. They should take those prescriptions that are only prescribed to
them and not for other people. Hygiene practices should be ensured between the
healthcare providers and patients (8).
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Conclusion
In conclusion, antibiotics resistance has been a challenge effacing humanity since
the first antibiotic, Penicillin was discovered in 1928.Despite the major changes have been
made on the penicillin beta lactam ring, bacteria have also developed mechanism of
resistant to counter that change. Resistance mainly occurs through mutations at the site of
action of the antibiotic. The main difference between gram positive and gram negative is
the thickness of the peptidoglycan layer and this can be seen through Gram staining. Gram
negative bacteria such as E.coli have been found to be more resistant to penicillin than
other bacteria. Theories have been developed to explain the cause of antibiotic resistance;
they are vertical gene and horizontal gene transfer. To reduce the rate at which resistance
to antibiotics occurs, the use of antibiotics should be restricted to serious cases where it
has been confirmed that a person has a bacterial infection. The use of feeds fortified with
antibiotics for broilers also contribute to resistance when they are taken by humans over a
long period of time.
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List of References
1. Coates, A. Antibiotic resistance; Springer: Heidelberg, 2012.
2. Bacterial Resistance to Antibiotics
http://textbookofbacteriology.net/resantimicrobial_3.html (accessed Oct 4, 2016).
3. Bonomo, R.Watkins, R. Antibiotic Resistance; Elsevier Health Sciences: Saintt Louis, 2016.
4. Flynn, E. Cephalosporins and penicillins: chemistry and biology; Academic Press: New
York, 1972.
5. Jones, G.Dever, S. The gram stain; U.S. Dept. of Health and Human Services, Public Health Service,
Centers for Disease Control: Atlanta, Ga., 1984.
6. Understanding antibiotic resistance; eScholarship, University of California, 2014.
7. (http://www.who.int/mediacentre/factsheets/fs194/en/). (accessed Oct 5, 2016).
8. Stewart, G.Holt, R. BMJ 1963, 1, 308-311.
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