HOME

TheInfoList



OR:

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
or condition. The term is used in the context of resistance that
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules (almost always proteins). Because the drug is ''so'' specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Furthermore, there is mounting concern over the abuse of antibiotics in the farming of livestock, which in the
European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...
alone accounts for three times the volume dispensed to humans – leading to development of super-resistant bacteria. Bacteria are capable of not only altering the enzyme targeted by antibiotics, but also by the use of enzymes to modify the antibiotic itself and thus neutralize it. Examples of target-altering pathogens are ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
'', vancomycin-resistant enterococci and macrolide-resistant '' Streptococcus'', while examples of antibiotic-modifying microbes are ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...
'' and aminoglycoside-resistant '' Acinetobacter baumannii''. In short, the lack of concerted effort by governments and the pharmaceutical industry, together with the innate capacity of microbes to develop resistance at a rate that outpaces development of new drugs, suggests that existing strategies for developing viable, long-term anti-microbial therapies are ultimately doomed to failure. Without alternative strategies, the acquisition of drug resistance by pathogenic microorganisms looms as possibly one of the most significant public health threats facing humanity in the 21st century. Some of the best alternative sources to reduce the chance of antibiotic resistance are probiotics, prebiotics, dietary fibers, enzymes, organic acids, phytogenics.


Types

Drug, toxin, or chemical resistance is a consequence of
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
and is a response to pressures imposed on any living organism. Individual organisms vary in their sensitivity to the drug used and some with greater fitness may be capable of surviving drug treatment. Drug-resistant traits are accordingly inherited by subsequent offspring, resulting in a population that is more drug-resistant. Unless the drug used makes sexual reproduction or cell-division or horizontal gene transfer impossible in the entire target population, resistance to the drug will inevitably follow. This can be seen in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
ous tumors where some cells may develop resistance to the drugs used in
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
. Chemotherapy causes
fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
near
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s to produce large amounts of the protein
WNT16 Protein Wnt-16 is a protein that in humans is encoded by the ''WNT16'' gene. It has been proposed that stimulation of WNT16 expression in nearby normal cells is responsible for the development of chemotherapy-resistance in cancer cells. Functio ...
B. This protein stimulates the growth of cancer cells which are drug-resistant.
MicroRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. mi ...
s have also been shown to affect acquired drug resistance in cancer cells and this can be used for therapeutic purposes.
Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...
in 2012 has become a resurgent threat in
South East Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainland ...
and
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, and drug-resistant strains of ''
Plasmodium falciparum ''Plasmodium falciparum'' is a unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female '' Anopheles'' mosquito and causes the ...
'' are posing massive problems for health authorities.
Leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...
has shown an increasing resistance to
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...
. A rapid process of sharing resistance exists among single-celled organisms, and is termed horizontal gene transfer in which there is a direct exchange of genes, particularly in the
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular po ...
state. A similar asexual method is used by
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
and is called " parasexuality". Examples of drug-resistant strains are to be found in microorganisms such as bacteria and viruses, parasites both endo- and ecto-, plants, fungi,
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s, mammals, birds, reptiles, fish, and amphibians. In the domestic environment, drug-resistant strains of organism may arise from seemingly safe activities such as the use of
bleach Bleach is the generic name for any chemical product that is used industrially or domestically to remove color (whitening) from a fabric or fiber or to clean or to remove stains in a process called bleaching. It often refers specifically, to ...
, tooth-brushing and mouthwashing, the use of antibiotics, disinfectants and detergents,
shampoo Shampoo () is a hair care product, typically in the form of a viscous liquid, that is used for cleaning hair. Less commonly, shampoo is available in solid bar format. Shampoo is used by applying it to wet hair, massaging the product into the ...
s, and soaps, particularly antibacterial soaps, hand-washing, surface sprays, application of
deodorant A deodorant is a substance applied to the body to prevent or mask body odor due to bacterial breakdown of perspiration or vaginal secretions, for example in the armpits, groin, or feet. A subclass of deodorants, called antiperspirants, prevents ...
s, sunblocks and any cosmetic or health-care product,
insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed t ...
s, and dips. The chemicals contained in these preparations, besides harming beneficial organisms, may intentionally or inadvertently target organisms that have the potential to develop resistance.


Mechanisms

The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are: # Drug inactivation or modification: e.g., enzymatic deactivation of ''Penicillin'' G in some penicillin-resistant bacteria through the production of β-lactamases. # Alteration of target site: e.g., alteration of PBP — the binding target site of penicillins — in MRSA and other penicillin-resistant bacteria. # Alteration of metabolic pathway: e.g., some
sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of
folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing a ...
and
nucleic acids Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid. # Reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell surface.


Mechanisms of Acquired Drug Resistance


Metabolic cost

''Biological cost'' is a measure of the increased energy metabolism required to achieve a function. Drug resistance has a high metabolic price in pathogens for which this concept is relevant (bacteria, endoparasites, and tumor cells.) In viruses, an equivalent "cost" is genomic complexity. The high metabolic cost means that, in the absence of antibiotics, a resistant pathogen will have decreased evolutionary fitness as compared to susceptible pathogens. This is one of the reasons drug resistance adaptations are rarely seen in environments where antibiotics are absent. However, in the presence of antibiotics, the survival advantage conferred off-sets the high metabolic cost and allows resistant strains to proliferate.


Treatment

In humans, the gene ABCB1 encodes MDR1(p-glycoprotein) which is a key transporter of medications on the cellular level. If MDR1 is overexpressed, drug resistance increases. Therefore, ABCB1 levels can be monitored. In patients with high levels of ABCB1 expression, the use of secondary treatments, like metformin, have been used in conjunction with the primary drug treatment with some success. For
antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
, which represents a widespread problem nowadays, drugs designed to block the mechanisms of bacterial antibiotic resistance are used. For example, bacterial resistance against beta-lactam antibiotics (such as
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...
and
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
s) can be circumvented by using antibiotics such as nafcillin that are not susceptible to destruction by certain beta-lactamases (the group of enzymes responsible for breaking down beta-lactams). Beta-lactam bacterial resistance can also be dealt with by administering beta-lactam antibiotics with drugs that block beta-lactamases such as clavulanic acid so that the antibiotics can work without getting destroyed by the bacteria first. Recently, researchers have recognized the need for new drugs that inhibit bacterial efflux pumps, which cause resistance to multiple antibiotics such as beta-lactams,
quinolones Quinolone may refer to: * 2-Quinolone * 4-Quinolone 4-Quinolone is an organic compound derived from quinoline. It and 2-quinolone are the two most important parent (meaning simplified) quinolones. 4-Quinolone exists in equilibrium with a mino ...
,
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, chole ...
, and trimethoprim by sending molecules of those antibiotics out of the bacterial cell. Sometimes a combination of different classes of antibiotics may be used synergistically; that is, they work together to effectively fight bacteria that may be resistant to one of the antibiotics alone. Destruction of the resistant
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
can also be achieved by phage therapy, in which a specific
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bac ...
(virus that kills bacteria) is used.


See also

*
Antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
* Fecal bacteriotherapy * Mass drug administration * Multidrug resistance * Pharmacoepidemiology * Physical factors affecting microbial life * Small multidrug resistance protein * ''
Eleftheria terrae ''Eleftheria terrae'' is a recently discovered Gram-negative bacterium. ''E. terrae'' is a temporary name for the organism, as it was only discovered in 2014 and is still undergoing scientific study. It was found to produce a previously unknown ...
''


References


External links


BURDEN of Resistance and Disease in European Nations
��An EU project to estimate the financial burden of antibiotic resistance in European hospitals


Cosmetics Database

HCMV drug resistance mutations tool


- An informative article on multidrug resistance


MDRIpred
: A web server for predicting inhibitors against drug tolerant M. Tuberculosis, published i
Chemistry Central Journal

CancerDR
Cancer Drug Resistance Database.

{{Authority control Immunology Psychopharmacology