FREE ESSAY ON ANITBIOTIC RESISTANT BACTERIA

ANITBIOTIC RESISTANT BACTERIA

Almost 60 years ago the first antibiotics were developed, and they were created at a time
when previously untreatable infections such as tuberculosis, gonorrhea, and syphilis
could be almost miraculously cured. Infections like these could be a death sentence, and
until recently they many be just that again. Microbes are learning the ability to fight
of these antibiotics and become resistant to them. They are gaining resistance through a
number of different ways, and science is in a race to keep up with there amazing
evolution. 
Bacteria are the common name for prokaryotic cells, which lack a nucleus. Rather they
have a nucleoid region where their DNA is stored in direct contact with their cytoplasm.
Their DNA, through transcription and translation, directs ribosomes to assemble proteins.
They reproduce by binary fission, and are mostly heterotrophic. Bacteria can exchange DNA
in three ways: transformation, transduction, and conjugation. In transformation a
bacterial cell becomes competent, or able to take up DNA from the surrounding fluids. In
conjugation two bacterial cells, a donor and a recipient join and DNA is transferred from
one to the other. In these cases the new DNA either incorporates itself into the existing
DNA or forms an independent molecule within the cell called a plasmid (Christensen). 
Antibiotics are substances produced by microorganisms that kill or inhibit other
microorganisms from growing or reproducing. Antibiotics are products of the earth and are
all-natural. 
For clinical purposes, bacteria are said to be resistant to an antimicrobial when they
are insignificantly affected by concentrations of the drug that can be achieved at the
site of the infection. As might be expected, achievable concentrations vary dramatically
from place to place in the body. Sensitivity of organisms to antimicrobials may be
quantified by the minimum concentration required to inhibit their growth (minimum
inhibitory concentration, MIC) or by the minimum concentration required to kill them
within a specified period of time (minimum bactericidal concentration, MBC). Because they
are easier to measure and apply to both bactericidal and bacteriostatic drugs, MICs are
more frequently used. Tables of typical MICs for many bacterial species/antimicrobial
pairs are widely available. When combined with knowledge of the time course of
antimicrobial concentrations at various sites in the body, these MICs can be used to
guide rational selection antimicrobials for particular infections. Application of this
rational approach to selection is still developing and unexpected results do occur.
Microbial resistance to antibiotics can be inherent or natural resistance. Bacteria may
be inherently resistant to an antibiotic. Other microbes developed acquired resistance.
This is when bacteria can develop resistance to antibiotics. So bacterial population's
previously sensitive to antibiotics become resistant. This type of resistance results
from changes in the bacterial genome (Stapleton). Two genetic processes in bacteria drive
acquired resistance: mutation and selection (or vertical evolution), or exchange of genes
between strains and species (or horizontal evolution) (Garrett 420).
Vertical evolution is essentiality Darwinian evolution, which is driven by natural
selection. So a spontaneous mutation in the bacterial chromosome imparts resistance to a
member of the bacterial population. In the presence of the antibiotics then, the wild
type (non-mutated) are killed and the resistant mutant is allowed to grow and flourish
(Garrett 421). The mutation rate for most bacterial genes is approximately 10-8. This
means that if a bacterial population doubles from 108 cells to 2 x 108 cells, and there
is likely to be a mutant present for any given gene. Since bacteria grow to reach
population densities far in excess of 109 cells, such a mutant could develop from a
single generation during 15 minutes of growth resistance to other strains and species
during genetic exchange processes (Levy).
The combined effects of fast growth rates, high concentrations of cells, genetic
processes of mutation and selection, and the ability to exchange genes, account for the
extraordinary rates of adaptation and evolution that can be observed in the bacteria. For
these reasons bacterial adaptation, or resistance, to the antibiotic environment seems to
take place very rapidly in evolutionary time (Stapleton).
Fleming first discovered penicillin, the first and most famous antibiotic, in 1929 when
he found that a Penicillium mold inhibited the growth of bacteria in a petri dish.
However, he failed to recognize the therapeutic potential of this and it remained for
Florey, an Englishman, to first use Penicillin for therapy in 1940. It was, and is, one
of the most active and safe antibacterials available. Because of their effectiveness and
large therapeutic index, penicillin and many closely related derivatives, collectively
known as the Penicillins, and the closely related Cephalosporines (discovered in the
1960s) are among the most important families of antibacterials available today.
Penicillium and Streptomyces are major sources of antibiotics used therapeutically.
Bacillus are the most notable bacterial group from which useful antibiotics have been
derived. Synthetic antimicrobials, e.g., the sulfonamides, have always constituted an
important source of antimicrobials. Semisynthetic antimicrobials are those derived from
chemical modifications of naturally occurring antibiotics. This constitutes an ever more
important group of antimicrobials as new drugs, with special properties, are developed.
The fundamental and most frequent grouping of antimicrobials is based on their chemical
structure. Each of the following groups has a structural component that defines the
group. Addition or subtraction of chemical groups from the core structure leads to the
various members of the group. Some key groups are: 
1. Beta-lactam antibiotics 
a. Penicillins: derivatives of 6-aminopenicillanic acid. e.g., penicillin G 
b. Cephalosporins: derivatives of 7-aminocephalosporanic acid, e.g., cephalexin 
2. Macrolides: have a large ring structure. Sometimes referred to as the erythromycins.
e.g., 
3. Lincosamides: name derived from the first member found, e.g., lincomycin 
4. Aminoglycosides: composed of aminosugars linked by glycosidic bonds to various bases.
e.g., gentamicin 
5. Tetracyclines: have a rigid structure composed of 4 fused benzene-like rings. e.g.,
tetracycline. 
6. Polypeptides: as the name says, aminoacids linked by peptide bonds form a major
component of the structure. e.g., vancomycin, 
7. Sulfonamides: derived from sulfanilamide, the first successful antibacterial, e.g.,
sulfadiazine. Trimethoprim is used to potentiate the sulfonamides. 
8. Fluoroquinolones: e.g., enrofloxacin (BAYTRIL) 
9. Miscellaneous: includes many drugs, such as chloramphenicol, nitrofurantoin, and
isoniazid that have only one or two representatives of the class and are seldom referred
to by their chemical nature in clinical practice. Antituberculosis and antileprosy drugs
belong to one or more of the classes listed here, including miscellaneous. 
To keep up with evolving bacteria, scientists are attacking efflux pumps. Efflux pumps
are what microbes use to rid themselves of toxic materials and drugs. The way science is
perusing this is to attach these pumps with compounds called efflux-pump inhibitors.
These compounds have no infection fighting power but can make current antimicrobial drugs
more effective (Christensen). Microbes that caused sickness in the preantibiotic era are
again making people sick because some of these microbes have become resistant to
antibiotics. Various bacterium are now resistant to one or more classes of antibiotics;
penicillins, cephalosporins, tetracyclines, quinolones, aminoglycosides, and macrolides.
These Bacteria can resist the drugs in several ways. They can alter it so that it's no
longer toxic. Or they can modify their own components so that the antimicrobial compound
can't bind to them nor have an effect on them (Garrett 432). 
Recently microbiologists have found that bacteria can also expel drugs, thus lowering the
internal concentration enough that the microbes escape the treatment's intended effects
(Christensen). 
Most efflux pumps probably evolved to handle toxins in the environment and only by luck
pump out antibiotics, and it is still unknown how these pumps work. Each pump is made up
of one or several proteins that span the cell membrane of the microbe. Two theories on
how efflux pumps actively expel a drug is through a local channel or by propelling the
drug across the cell membrane. Efflux pumps are known to be responsible for a moderate
level of resistance in many different species of bacteria and against several drugs. Not
all microbes have efflux pumps, and the ones that do employ widely varying numbers and
types. Some microbes always have abundant pumps, and others manufacture additional pumps
after exposure to drugs (Christensen).
Efflux pumps help explain why some bacteria are less susceptible to drugs than others
are. Some species of bacteria seem to use efflux pumps to resist tetracyclines,
macrolides, and fluoroquinolones well enough to often make these antibiotics useless
weapons. "Since efflux pumps can act on more than just one kind of antimicrobial agent,
microbes may develop resistance against several different drugs simultaneously"(Tulkens
in Christen). Between 40 and 90 percent of some bacterial pathogens carry efflux pumps
for most of the major classes of available antibiotics (Christensen).
With the information now known, efflux pumps opens up opportunities for pharmaceutical
companies to find compounds that will disrupt this microbial activity. As drugs,
efflux-pump inhibitors aren't expected to have a significant antimicrobial effect on
their own and companies are now developing these compounds. They are expected to reverse
acquired drug resistance in microbes that are susceptible to antibacterial and antifungal
drugs. Also efflux-pump inhibitors might make some microbes that are intrinsically drug
resistant vulnerable to antibiotics, and those efflux-pump inhibitors will reduce the
chance that bacteria will successfully reproduce enough times to select for a
drug-resistance mutation (Christensen).
Efflux pumps are not the only problem, many bacteria were capable of using sporulation to
their advantage in the face of' antibiotics and other threats. Like plant seeds, they
would go dormant, toughen their cell walls to a nearly impermeable state, and wait. When
conditions were favorable, the bacteria would reactivate, their cell walls once again
becoming permeable. Some forms of resistance involved the bacteria's use of genes that
triggered sporulation when the microbes were threatened, or created an even less
vulnerable cell wall at the time of sporulation (Garrett 428).
Under such conditions, microbes could drift about unharmed in solutions designed
specifically to kill them. Sporulation mutants can withstand all disinfectants, such as
chlorine- and ammonia-based cleansers, soaps, extremely salty or acid solutions, and even
high heat. 
An example of this would be a number of organisms, including strains of cholera, E. colt,
and the Legionnaires' disease bacteria, had developed some resistance, through such
sporulation mechanisms, and other means, to chlorine. They are partially tolerant, not
all together resistant, because the microbes were able to survive in doses of chlorine
that usually killed their species. To ensure safe drinking water in the presence of such
bugs, higher doses of chlorine were needed (Garnett 428)
At drug and biotech companies across the United States, scientists have set their sights
on a most elusive target: drug-resistant microbes. Working in pharmaceutical-
biotechnology partnerships, researchers are trying every trick in the book-including
high-tech drug discovery, genome sequencing, and development of new vaccines-to overcome
resistant pathogens. Successful companies stand to gain a significant share of the $23
billion antibiotics market(Brown).
A handful of new or improved antibiotics geared to resistant bugs are in various stages
of clinical trials, and ideas for novel therapeutics abound. Like, resistance-related
genes may lie within human and bacterial genomes currently being sequenced in various
large-scale projects. According to a newly released World Health Organization (WHO)
annual report, drug-resistant strains of microbes have evaded common treatments for
tuberculosis (TB), malaria, cholera, and pneumonia. The widespread use of antibiotics
contributes to drug resistance. The longer bacteria are exposed to a drug, the more
likely they are to evolve a way around it. Today, 160 antibiotics, all based on a few
basic chemical structures, are on the market. Researchers suggest these drugs may be
overprescribed. Patients often fail to complete antibiotic therapy; they stop taking
drugs as soon as they feel better. Bacteria still in the body can rebound, developing
resistance to the drug at hand in the host's system. Such misuse of prescriptions,
combined with societal conditions-such as the growth of day-care centers and increased
long-term care in hospitals-provides an environment where drug-resistant microbes can
emerge and thrive (Brown). 
Science, is many fields, is working on a varying answer for this problem. But they must
work fast to counteract the problem, because is the microbes become resistant to are
antibiotics, where does that leave us? Extinct (Magee)! 
Bibliography
Brown, Kathryn. The Scientist, Vol:10, #12, p.1, 8-9 , June 
10, 1996.
Christensen, Damaris. "Keeping Bugs from Pumping Drugs." 
Science News 157 no7 F 12 2000.
Garrett, Laurie. The Coming Plague. New York: Farrar, 1994.
Levy, Stuart B. Antimicrobial resistance. British Medical 
Journal, Sept 5, 1998 v317 p612.
Magee, J T. "Antibiotic Prescribing and Antibiotic 
Resistance in Community Practices." British Medical 
Journal, Nov 6, 1999 v319 i7219 p1239.
Stapleton, Stephanie. "Counterattack (Antibiotics and 
Bacteria)." American Medical News, June 1, 1998 v41 
n21 p31(1).