The Molecular Mechanism That Make Staphylococcus Aureus Resistant To Antibiotics - Essay Example

? The Molecular Mechanism That Make Staphylococcus Aureus Resistant To Antibiotics ID Introduction, An antibiotic is asubstance that kills bacteria by disrupting a critical function, usually coded by a definite protein in the bacteria. Once this critical function is affected the bacteria cannot carry out its normal functional roles, and it is eliminated from the ecosystem. Antibiotics bind to proteins making them lose theirs capacity to carry out normal functions. Proteins normally replicate DNA, resulting in cell walls for bacteria or proteins for definite purposes. According to Talaro (2006), these processes are extremely vital in the functioning of bacteria. On the other hand, if bacteria develop resistance to antibiotics, then the drugs’ ability to stop or control their growth fades away; hence, bacteria continue to thrive even when they are exposed to them. This is caused by molecular mechanisms of the bacterial species that render the antibiotics functionless. The resistant species cause infections which cannot be treated with the usual formerly effective drugs, dosages and concentrations that treated the disease successfully. This resilience might be caused by internal mechanisms or acquired from other external sources. Resistance to multiple antibiotics as shown by some pathogens is called Multidrug Resistance (MDR). A term superbug has now been coined and is used to refer to the same. Microorganisms have an important trait of being able to adapt fast to their environment hence can survive for a long time without being eliminated. Disease causing pathogens have become a serious threat in medicine due to their resistance to antibiotics. Some of these diseases include tuberculosis, malaria, gonorrhea and childhood just to mention a few. They have become hard to treat due to the antibiotic resistance of their causative organisms. They become resistant, developing mechanisms that enable them to withstand the effects of chemicals meant to abate or destroy them. This poses a threat because once it happens the drug has to be replaced or modified for it to continue functioning. Antibiotics cause an increase in selective pressure when used in an environment with a large number of bacteria. The result is that as weak bacteria succumb resilient ones continue to survive. There are different lines of antibiotics such as first, second and possibly third. Drug resistant microorganisms may have acquired resistance to the first line of antibiotics hence causing the need to use the second line of antibiotics. The first line of these antibiotics is usually selected based on several advantageous factors which include safety, availability and their cost. In contrast the second line agents usually have a broader spectrum compared to those in the first line. They possess a less favorable risk benefit to the users and maybe more expensive and not accessible in the local marketplace. Resistance to the second and occasionally to the third line of antibiotics is usually acquired in a sequential manner (Bauman, Machunis-Masuoka, and Tizard, 2004). This is usually well illustrated by a bacterial strain called staphylococcus aureus, which is discussed abundantly in this essay. Resistance may be due to mutation which can either be spontaneous or induced by other factors. It may also be through gaining resistant genes from other resistant bacterial species. This is through horizontal gene transfer which may occur through conjugation, transduction or transformation. These antibiotic resistance genes usually reside on the plasmids expediting their transmission. Contact with antibiotics necessitates natural selection, leading to the survival of organisms with resistant genes. This causes the gene for the antibiotic resistance to spread easily through an ecosystem of bacteria. Staphylococcus Aureus Staphylococcus aureus is a bacterium that has shown resistance to antibiotics for a long period. This resistant pathogen is located on its hosts’ mucous membranes and human skin, is extremely resistant and adapts to antibiotics easily. Staphylococcus aureus was the first bacteria to develop resistance to penicillin; this happened within the first few years of discovery of the drug. During this time, methicillin was the preferred antibiotic. It has since been substituted with oxacillin because it is highly toxic to the kidney. Buhner (1999) states that Methicillin Resistant Staphylococcus (MRSA) causes multiple diseases that pose a formidable challenge to medical practitioners. This has earned the bacteria the names Multidrug Resistant Staphylococcus Aureus (MRSA) and Oxacillin Resistant Staphylococcus Aureus (ORSA). The former has developed through the process of evolution where nature took its cause. It includes resistance to beta lactam antibiotics such as penicillin and cephalosporin. Other strains that are unable to resist the antibiotics are called methicillin sensitive staphylococcus aureus (MSSA). Infections due to Staphylococcus Aureus mostly happen when mucosal barriers or the skin are broken. It is the common source of staph contaminations and is responsible for numerous types of diseases which include mild skin infections, invasive diseases and other toxin mediated diseases. Microorganisms become resistant to multiple drugs because of the following reasons: They do not rely on glycoprotein cell walls, They deactivate antibiotics using enzymes The permeability of their cell walls to antibiotics is low The antibiotic’s target sites are altered They have large mechanisms of eliminating antibiotics They mutate faster as they react to stress. Staphylococcus aureus has developed several molecular mechanisms that cause it to become resistant to antibiotics. These: Horizontal gene transfer Mutation Recombination These factors, which occur naturally, or are induced, elicit diversification within the staphylococcus aureus population that helps them develop resistance to antibiotics. Horizontal Gene Transfer (HTG) This is the relocation of hereditary material from one species to the neighboring species. Staphylococcus aureus can transfer copies of codes of their DNA to other bacteria; hence, carrying along their resistance mechanisms. This enables them to transfer resistance to neighboring bacteria. They possess the ability to impart resistance on other bacteria that also become resistant to the same antibiotic (Gomes, et al., 2001). This is also called horizontal gene transfer and it contrasts the normal vertical gene transfer. Staphylococcus Aureus employs this technique in gaining resistance and degrading noble compounds meant to kill it. Horizontal gene transfer can occur either through conjugation, transduction or transformation. These bacteria have large gene pools that can modify their blueprints. This further enhances their existing resistance against antibiotics harmful to them. These involve plasmid which carries genes responsible for antibiotic resistance. These genes can be transferred to another bacterium through various mechanisms, including pilus, and in the process, arming the antibiotic resistant genes in the recipient bacteria. During HGT, bacteria engage various mechanisms that make them resistant to antibiotics. One of the methods is conjugation. This comprises the acceptance and expression of extraneous RNA/DNA through plasmids that are conjugated. Plasmids function independent of chromosomal DNA. They usually have two strands and look like circles. These plasmids carry vital guidelines that present discerning benefits to the bacteria. Staphylococcus Aureus can replicate these plasmids for sharing the nearby bacteria. They may permit the bacteria to synthesize beta lactam, an enzyme that can cleave antibiotics such as penicillin, thus rendering them useless. Another method in HGT is transduction. In this case, viruses, called bacteriophages, transfer genetic material from one bacterium to another. Bacteriophages do kill bacteria, but can also play a crucial role in the gene transfer allowing the bacteria to gain resistance. Transduction does not require donor cells and recipients to be in contact. It is a common tool that molecular biologists use to manipulate genomes by introducing external DNA into them. When these phages infect bacterial cells, their normal mode of production partakes the replication, transcription and translation mechanisms of the cell that accommodates them; hence, they develop several virions or viruses such as protein coats and DNA/RNA. Transduction is particularly significant as it clarifies the procedure through which antibiotics become ineffective in their work. This is due to the transfer of antibiotic resistance genes. Diagram showing the transduction process Transduction occurs either through the lytic or lysogenic pathways. Phage chromosomes integrate with bacterial chromosomes in the lysogenic cycle; in this state of fusion, phage chromosomes can become inactive over a long period. Once the lysogen is induced, by UV, for example, genomes are removed from bacterial chromosomes. This initiates a lytic cycle which releases the phage chromosomes. These are then removed from the host through lysis. In generalized transduction, only the bacterial DNA and no viral DNA are carried. It can, therefore, be considered as the wrapping of bacterial genetic material into a viral envelope which can either occur through recombination and headful packaging. In case of a lytic cycle of infection, the viruses take control of the cell`s machinery using them to replicate their own viral DNA. Inserting chromosomal DNA into the viral capsid is an error that leads to generalized transduction. According to Russell and Cohn (2012), any replication of the virus makes it attempt to fill nucleocapsids with genetic material. Packaging may be done by including bacterial DNA into the resultant virion if the genome has extra space. The resultant virus capsule, which partially contains bacterial DNA, infects other bacterial cells around it. It may also recombine with other bacteria when infection occurs. When inserting DNA into host cells it may undergo the following experiences: The cells may absorb and reuse them to make auxiliary parts Those that were plasmid circularize within their hosts and regain their initial form If it matches with a homologous region of the recipient cell`s chromosome, it will exchange DNA material; this is similar to the processes that take place in conjugation They recombine randomly, a process that is influenced by and the amount of virus used. Specialized transduction is where restricted sets of bacterial genes are transferred to other bacteria. This depends on the location of the phage genome on the chromosome. It occurs when the prophage leaves the chromosome, making bacterial DNA located next to the prophage to be eliminated from the new DNA. The genetic material is then packed into a new virus that delivers the DNA to other bacteria. The recipient chromosome in the other bacteria can either interact with the DNA or let it remain in the cytoplasm. A heterogenote results when an encapsulated phage infects another cell, coding its prophage DNA partially. The third method of heterogeneous gene transfer is conjugation. In this case, genetic materials are transferred directly between cells through contact; bacteria can use sex pilus to transmit genomic substances to other bacteria. However, not all bacteria practice all the three methods since they vastly depend on their physiological characteristics, and genetic construct. Diagram showing a schematic diagram of how bacterial conjugation occurs. The HTG is usually beneficial to the bacteria, but to medicine it poses a threat. The spread of antibiotics resistance among similar organisms is increasing at a high rate. This occurs mainly through bacterial cooperative sharing, a concept known as horizontal gene transfer. Mutation Mutation is another mechanism by which staphylococcus develops resistance to antibiotics. There are alterations occurring accidentally in genomic sequences of DNA, DNA sequences of cell genomes, or RNA and DNA sequences of some viruses. Thapa (2012), states that these sequences are random, because of their rapid and unstructured nature. The causal agents of mutation include viruses, radiation, tyransposons, mutagenic chemicals, and errors due to meiosis and gene replication. It can also be stimulated by the entity itself through bicellular processes such as hypermutation. Antibiotics always bind to proteins making them function abnormally. Normally, proteins copy DNA, make other proteins or in some cases making the bacterial cell wall. The primary functions of bacteria are growth and reproduction. Bacteria with mutated DNA that has similar codes to any of the proteins cannot bind with the antibiotic; these mutant bacteria can then survive any exposure to the antibiotic. Therefore, natural selection occurs in the presence of antibiotics, resulting in the survival and development of bacteria that are highly mutated. The inefficiency of the manipulated protein in performing its functions makes bacteria unable to thrive in the absence of antibiotics. This makes non mutant bacteria better than mutants in competing for resources and reproduction, naturally selecting from such an environment. In addition, staphylococcus may become sturdy to antibiotics by acquiring transfigured DNA from other microorganisms. This mechanism of exchanging DNA helps bacteria to survive adverse environmental conditions and develop resistance to antibiotics applied to them (Holmes and Jobling, 1996). However, as stated earlier, their proteins become defective and lose their normal function as this occurs. This is, therefore, considered as just a variation of kinds of bacteria, and not as evolution. In some other types of mutation, bacteria secrete enzymes that incapacitate antibiotics. Others eliminate sections of cells that antibiotics target by making them inactive; hence, the drugs cannot bind to them. Some close up points through which antibiotics get into the cells while others develop ways that they use to pump antibiotics outside them; antibiotics, therefore, never reach their target. Another process that enables staphylococcus aureus to develop antibiotic resistance is recombination. It is the creation of unusual DNA sequences through the development of new genetic sequences by the creation of two DNA strands. It is, however, an official way, but can develop resistance. Conclusion Increased use of antibiotics is leading to an equivalent proliferation in resistance of bacteria to antibiotic drugs. The overuse or misuse of antibiotics is one of the key factors that boost the creation of the superbugs described above such as Methicillin Resistant Staphylococcus Aureus. They are collections of Staphylococcus Aureus which are unaffected by methicillin and various antibiotics. This evolves many of these bacterial diseases into serious threats as their causative agents are always in a constant move to adapt. They become resistant to already available and previously effective antibiotics. Multidrug Resistant Staphylococcus Aureus are exceedingly difficult to treat due to the resistance of their causative pathogens. Other issues that promote resistance to antibiotics include patients failing to follow prescriptions involving antimicrobials fully, or use of poor quality of antimicrobials; these can fast-track the emergence and spread of resilient bacteria. If definite measures are implemented to curb the use of antibiotics, then we can be able to succeed in controlling the antibiotic resistance. Measures should be instituted to manage the administration of empiric antibiotics. Creating limits to a broad spectrum of drugs also minimizes the drug resistance. In addition, formularies to previously operative antibiotics can aid the control of resistance to antibiotics. Bibliography Bauman, R. W., Machunis-Masuoka, E., and Tizard, I. R., 2004. Microbiology. London: Pearson Benjamin Cummings. Buhner, S. H., 1999. Herbal antibiotics: Natural alternatives for treating drug- resistant bacteria. North Adams, MA: Storey Publishing. Gomes, A.R., Santos, I., Sanches, M., Castaneda, E., and Lencastre, H., 2001. Molecular epidemiology of methicillin-resistant staphylococcus aureus in Colombian hospitals: Dominance of a single unique multidrug-resistant clone. Microbial Drug Resistance, 7(1): 23-32. Holmes, R. K., and Jobling, M. G., 1996. Genetics: Conjugate. In: Baron`s medical microbiology. Texas: University of Texas Medical Branch. Russell, J. and Cohn, R., 2012. Methicillin-resistant staphylococcus aureus. Stoughton, WI: Book on Demand Ltd. Talaro, K. P., 2006. Foundations in microbiology. 6th ed. Columbus: McGraw-Hill Higher Education. Thapa, S., 2012. Methicillin resistant staph. Aureus in pediatric patients of Nepal: Prevalence and antibiotic susceptibility pattern. New York: Lap Lambert Academic Publishing. Read More