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Antibiotics are powerful tools that were developed to fight against the dangerous and disease causing pathogens. Antibiotic resistant microbes are becoming a dangerous threat to the mankind day by day. Increase in microbial resistance to more commonly used drugs is a major hurdle for the present generation of researchers and doctors. These antibiotics are nothing but drugs that have the capability to kill or to reduce the bacterial activity4, which helps the patient to recover from illness. Most of the bacteria are becoming resistant to drugs through the genetic changes like mutations within the bacteria1. Some major studies revealed that the resistance in these micro organisms were developed either through mutation, gene transfer or selection. These resistant bacteria have also become an economic burden to most of the developed and developing nations1. Antibiotics once used to control diseases and causing agents have become useless by the changes within the bacterial resistance mechanisms3. In most of the studies it was found that, one of the reasons for the microbes to develop the resistance against drugs is the unnecessary usage of antibiotics than required2. Some of the antibiotics that are used earlier in general are penicillin, for most of the Staphylococcal infections in hospitals oxicillins6 is used and fro urinary tract infections ampicillin and sulphonamides are used. There is a greater demand for new methods or antibiotics in order to win the battle against these disease causing agents.
While looking past into the history of antibiotic resistance, the bacterial strains that are resistant to the antibiotics are first found in hospitals. In the early 1930s, the bacteria Streptococcus pyrogenes which is resistant to Sulphonamide was first found in military hospitals. After the introduction of penicillin in 1940s3, penicillin resistant Staphylococcus aureus was identified at Civilian hospitals in London in the year 1944. Staphylococcus aureus was resistant to penicillin by releasing an enzyme called Î²-lactmase8. Another antibiotic resistant bacterium that was found in the same period is Mycobacterium tuberculosis. This bacterium is resistant to the antibiotic Streptomycin. In early 1950s -1960s multiple drug resistant bacteria had become a major problem and were first identified in enteric bacteria3. Haemophilus Influenzae which causes respiratory diseases was found to be resistant to ampicillin, chloramphenicol and tetracycline.
In 1980s Methicillin which is a semi synthetic form of penicillin resistant Staphylococcus aureus was found in majorly in the hospitals of United Kingdom, Poland, France and some other European countries5. This bacterium is called as MRSA (Methicillin Resistant Staphylococcus Aureus). A protein called penicillin binding protein (PBP) is produced by a gene called mecA makes it to have low affinity towards Î²-lactam antibiotics8. This characteristic nature made MRSA resistant to all penicillins, cephalosporins, penems and carbapenems. These antibiotic resistance characteristics are passed from one organism to other. Until 1996 vancomycin is considered as an effective drug for treating MRSA, but later a vancomycin resistant MRSA is identified in Japan11. Linezolid, a new antibiotic for MRSA was introduced in the year 2000, but this one also failed as a linezolid resistant MRSA is identified in Boston11.
Development of Antibiotic Resistance:
Antibiotic resistance in bacteria is acquired through different ways. In case of most of the bacteria the common ways are through genetic mutations within the bacteria in order to develop a new trait or new enzymes that can add some resistance in its defence mechanism. One of the interesting characteristics of these organisms is the ability to accumulate the antibiotic resistant genes from other microbes1. This accumulation of resistant genes can be done in different routes like transfer of genes through plasmid or viral particles, grasping required genes from its environment left by the dead bacteria. The gene transfer it can survive the antibiotic effect it is transferred through a plasmid or a chromosome only. There resistant genes are embedded into a smaller portion of DNA called transposons. This mechanism helps in the easy transfer of the transposons into other DNA molecules. (Fig1). In some cases the bacteria performs the gene transfer through highly advanced form of a transposons called integrons. These integrons are mobile DNA elements1. These integrons capture the antibiotic resistance encoding genes through a process called site specific recombination.
Figure 1: Different modes of pick up and transfer of resistance genes. (Source: ref-1)
As a known fact that, not all the bacteria are harmful. There are some types of bacteria that are very helpful. When a drug (antibiotic) acts on a group of bacteria, there are chances for the drug to act on the useful bacteria as well along with the disease causing pathogens. The useful bacteria which are resistant in nature develop more resistance due to the action of drugs and transfer its resistance to other disease causing bacterial pathogens. One of the antibiotics of this type is the wide use of cephalosporin. This antibiotic lead to the penetration of E. faecalis2, that is naturally resistant leads to a deadly systematic disease in an immunity compromised individual.
Mechanism of Antibiotic Resistance:
The antibiotic resistance mechanism varies from one group of bacteria to other. Bacteria exhibit their defence mechanism through different ways. The genes in the bacteria might code for efflux pumps, new enzymes or through chemical alteration2.
In some of the bacteria the genes that are acquired from other bacteria or developed by itself through mutations codes for antibiotic degrading enzymes. These enzymes are generated and are activated by the action of antibiotic on the bacteria. Some of these enzymes are Î²-lactamses, which degrade antibiotics like penicillin and cephalosporin. Another type of resistance mechanism is the production of enzymes that alter the chemical characteristics of the antibiotics and turns them into in active form. In case of antibiotics like streptomycin and gentamicin, these modifying enzymes act on chloramphenicol and amino glycosides10.
Antibiotic efflux pumps in another form of resistance exhibited by the bacteria in order to overcome the antibiotic attack1. In this mode the antibiotic that entered into the bacterial cell exits through a separate channel called the efflux pump. In this the antibiotic enters and exits without causing any damage to the bacterial cell. By this mechanism the bacteria develops resistance to drugs like tetracyclines, chloramphenicol and flouoroquinolones. (Fig2).
Figure 2: Modes of action on antibiotic resistant bacteria on antibiotics (Source: ref-1)
Another important mode of action performed by the bacterial defence mechanism is intracellular target alteration of the drug. In this the enzymes or other factors alters the ribosome or metabolic enzymes or proteins that are involved in replication of DNA or cell wall synthesis, resulting in blocking or inhibiting the action of drug on the bacteria8.
In a research on continuous application of tetracycline for urinary tract infections it was found that the bacteria developed resistance not only to a single drug but also to other types.
Prevention of Drug Resistance:
One of major reasons for increase in antibiotic resistance in bacteria is the usage of drugs that are more than required and no systematic regulation in the antibiotic prescription to the patients. In a research survey it was calculated that out of 150 million people, 50 million of outpatients with suggested usage of antibiotics are nor not necessary. While in case of United Kingdom it was found that in between the years 1995 and 2000, 22% antibiotic reduction is seen in communities and during 1993 and 2003, 50% of reduction is seen in paediatric prescriptions9.
Some serious steps have to be taken effectively in order to control the antibiotic resistance. There should be a continuous monitoring in the frequency and resistance distribution. Researchers have found that Commensal organisms were found to be the major reservoirs for antibiotic resistance plasmids, genes and transposons3. These organisms have to be tracked continuously so that their resistance levels can be calculated effectively. The patients who are hospitalized by an attack of dangerous antibiotic resistant bacteria they have to be isolated and treated separately. So these may reduce chances of antibiotic resistance in other microbes of that environment. Drugs have to be used appropriately and effectively so that the drug can work can work effectively on the pathogen1. While reducing the usage of antibiotics in hospitals shown that the microbial population to reproduce, in the absence of the antibiotics. Developments of new drugs that are effective in complete elimination of the pathogenic bacteria are highly essential.
Apart from these some simple can easy procedures have to be followed by both physicians and patients. The doctors have to prescribe antibiotics which acts only on a bacteria of specific type. Patients with multidrug infections have to be isolated from the rest and have to be treated effectively1. While in case of patients and general public antibiotics should not be used without proper prescription. Prescribed antibiotics have to be consumed according to the treatment plan as advised by the doctor2.