Antibiotics, quintessentially are a certain type of drug that’s sole purpose is to combat against the growth and spread of harmful bacteria in the human body. They include a variety of certain types of pharmaceuticals that help the human body quell infections caused by these bacteria such as the common cold or the flu. They are a powerful type of medication that when administered properly has the ability to cure infections that plague the human body (Nordqvist, 2017). The discovery of natural antibiotics by Alexander Fleming propelled the idea of antibiotics to greater heights, it enabled the effective control of infections caused by Gram positive pathogens such as Staphyloccocus and Streptococcus and the isolation of streptomycin in 1943 aided the control of tuberculosis agent Mycobacterium tuberculosis being the first ever to do so in history (Brown & Fraser, 2016). However, another aspect of antibiotics also has to be considered, and that is the resistance of antibiotics as we continue to utilise the drug in the fight against infections of the human body.
Antibiotics disrupt the biochemical processes of the body, this eventually culminates into restriction of cell growth and division, and relative to bacterial agents will result in death. Research indicates that through the awareness of how exactly antibiotics kill bacteria can the scientific community then improve existing medication. This is also beneficial as there has been a lack of antibiotic development in the last 40 years and many bacteria that was initially targeted by antibiotics has since advanced in their ability to resist antibiotics (Brown & Fraser, 2016). Dr James J Collins, a professor of Biomedical Engineering and the William F Warren Distinguished Professor at Boston University discovered three types of antibiotics, the quinolones, beta-lactams, and aminoglycosides all kill bacteria by producing hydroxyl radicals. These hydroxyl radicals are highly developed molecules that attack any kind of cell components, such as lipids, proteins and DNA, but most importantly, it is the hydroxyl-induced DNA damage to guanine, one of four nucleotides that results in cell death (Paddock, Collins & Walker, 2012).
For any curative channel, there will always be a worry of the likelihood of resistance. This holds true in the case of antibiotic treatment against diseases of the human body. It is hard to pinpoint what may be the cause for this resistance, this could include many biochemical or physiological mechanisms, this can also be attributed to the lack of knowledge on the topic of antibiotic resistance which is a primary reason that there is little significant progress in the control of resistance development (Davies & Davies, 2010). Bacterial resistance to antibiotics can be traced back to World War II, when antibiotics were first prescribed in the 1940’s. Penicillin was successful in controlling bacterial infections among soldiers in World War II. Soon, pencillin resistance emerged as a significant issue, such that by the turn of the decade, developments in the antibiotic scene was vulnerable. The new beta-lactam antibiotics were invented, and used to fight against the new resistance that had surfaced (Chattopadhyay, Sengupta & Grossart, 2013). However, resistance has developed in almost all of known antibiotics, causes include,
When Sir Alexander Fleming first discovered penicillin, he had raised concerns over the potential overuse of the drug, “public will demand [the drug and] … then will begin an era … of abuses.”. Epidemiological studies have shown direct correlation between antibiotic utilization and the evolution and spread of resistant bacteria strains. In the case of bacteria, genes can be inherited from related species or can be attained through nonrelatives by mobile genetic elements such as plasmids. This process called horizontal gene transfer (HGT) can spread antibiotic resistance among different species of bacteria, but can also be derived spontaneously through mutation (Read & Woods, 2014)
2. Inappropriate Prescribing
Incorrectly administered antibiotics are among a leading cause for bacterial resistance against antibiotics. Studies prove that treatment indication, choice of antibiotics, and the time of the antibiotic course is incorrect in 30 to 50% of cases, furthermore, 30 to 60% of prescribed antibiotics in intensive care units (ICU) have been proven to be unnecessary (Luyt et al, 2014). Incorrectly prescribed antibiotics ambiguous benefits to patient health and might leave patient’s health vulnerable to possible complications of antibiotic remedy. Subinhibitory and subtherapeutic antibiotic concentrations can stimulate antibiotic resistance by advocating genetic alterations, including changes in gene expression, HGT and mutagenesis. Changes in antibiotic-influenced gene expression can promote virulence, while increased mutagenesis and HGT advocate antibiotic resistance (Viswanathan, 2014).
In an annual report on universal risks, the World Economic Forum (WEF) states that, “arguably the greatest risk … to human health comes in the form of antibiotic resistant bacteria.” (Howell, 2013). Conventional methods of disease control and antibiotic developments are vital to the fight against antibiotic resistance, however antibiotic resistance and the downfall of research and advances in antibiotics continue to decline despite all remedial efforts. All future approaches are fundamentally built on the fact that these prokaryotes (bacteria) created antibiotics millions of years ago, and the resultant resistance is attributed to adaptation to the antibiotics (Spellberg, Bartlett & Gilbert, 2013). Current methods specifically target the compounds that combat against logarithmic multiplying bacteria (Coates et al, 2002). This is illustrated through the discovery of the natural antibiotic, Penicillin which was discovered through scientific observation (Fleming, 1929, Abraham, 1987) or through the exploration of similar antibiotics (Pelaez, 2006). These natural antibiotics have aided in the production of analogues for chemists and have provided chemists with the basic structure of 6-aminopenicillanic acid (Rolinson & Geddes, 2007). This method has been very lucrative in the development of new antimicrobial agents (Zhanel et al, 2004, Zuckerman, 2004). Novel antibiotics have also been developed from the artificial pathway, although derived from quinine. Compound collection screening is also utilised with enzymes or entire cells, for example target deregulation by antisense RNA (Wang et al, 2006) but have not resulted in any marketable drug.
Future approaches towards the fight against antibiotic resistance have to be considered and quickly put into action, this also includes photodynamic therapy which has proven to be effective in an experiment conducted by Dai et al where a mouse model infected by the Methicillin-resistant Staphyloccocus aureus (MRSA) infection that has become resistant to antibiotic treatment and bioluminescent strains of the bacteria was used to track the progress of the infection. The experiment resulted in a conclusion where photodynamic therapy could be used as an alternative approach for treatment of MRSA skin infections and could aid the fight against antibiotic resistance immensely. (Dai et al, 2010)
Methods that have been proposed to potentially develop newer and more improved antibiotics include:
1. Natural compounds such as non culturable bacteria as targets
Antibiotics currently being sold in the market such as streptomycin have come from bacteria that thrives on artificial solid or liquid mediums. Antibiotics in the market are not isolated from non culturable bacteria, as growth on solid media has been a vital step towards the development of antibiotics. Currently, cloning large fragments of non-culturable bacterial genome and to manifest them through recombinant DNA technology (Turnbaugh et al, 2006, Lee et al, 2007). DNA is obtained from a cocktail of bacteria and is then put into a vector, for example a bacterial artificial chromosome that accepts large DNA fragments. Open reading frames within the fragment are then conveyed in a culturable cell and is then tested for antimicrobial activity. However, disadvantages include productive DNA fragments occur too infrequently for cloning (Coates & Hu, 2007)
It is approximated that every 2 days, half of the bacterial population are being destroyed by bacteriophages (Hendrix, 2002). Therefore, bacteriophages have been used as antimicrobials in certain countries such as the United States and countries of the former Soviet Union to treat infectious diseases. (Sulakvalidze et al, 2001). Bacteriophages have been developed in the poultry and cattle industry, aquaculture and the sewage treatment (Sheng et al, 2006, Doyle and Erickson, 2006, Nakai & Park, 2002, Withey et al, 2005). Advantages include the mechanism of which bacteriophages operate would be entirely different to that of the antibiotics currently in the market now. At the other end of the spectrum, quality control and standardisation is different, and when administered in patients, bacteriophages may be immunogenic and have the potential to induce neutralising antibodies (Dabrowska et al, 2005)
The exploration of new and improved antibiotics is in high demand in our era, it is imperative that if our medical development were to continue to progress, so should enhanced antimicrobial agents. Antibiotic resistance is a substantial threat to our human health, and as we enter another decade, the scientific community should look into different means of discovering antibiotics such as photodynamic therapy or bacteriophages to break new ground in the exploration of novel compounds.
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