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1004BMS Antibiotic Resistance: are antimicrobial peptides a solution?

Antibiotic resistance is when bacteria develops ways to resist antibiotics since occurs because bacteria need to ensure that they survive (Stuart et al., 2002 Page number). Bacteria has evolved to acquire and maintain supplemental DNA that as accessory pieces, is separate to the chromosome itself. This is a plasmid. These plasmids are independent and they are self-duplicating genetic components that carry as little as three genes and as many as three hundred different kinds of genes (Stuart B et al., 2002). Globally, antibiotic resistance has become a big threat to our health. Resistance has threatened the ability to be able to treat infections. This is due to antibiotics being over prescribed by health medical professionals. (World Health Organisation 2018). Due to the genetics of antibiotic resistance such as, mutations, gene pickup, HGT and heterologous expression overusing antibiotics makes them less effective, so they are no longer used routinely to fight infections (National Health Service 2016) (Davis et al., 2010) If antibiotics are used to treat conditions that are trivial, it is less likely that antibiotics will be able to treat serious conditions (National Health Service 2016). Therefore, there is no need to prescribe antibiotics as much as we have been in recent years. Prescribing large amounts of antibiotics isn’t the only concern, the duration that antibiotics are prescribed for can affect the environmental and therapeutic effects (Stuart B et al., 2002page number). Increasing resistance can arise when poor practices such as infection control are not practiced properly. (Frieri et al., 2002) When infection control is not practiced properly, resistant bacteria can be spread easily to other environments and to other people (Frieri et al., 2016). Without new drugs to overcome antibiotic resistance, diseases like Tuberculosis (TB) could become untreatable and could become fatal (World Health Organisation 2014). In recent years despite the progress of treating and preventing Tuberculosis, in 2012 8.7 million people developed TB and 1.3 million people died from the disease (World Health Organisation 2014).

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1004BMS Antimicrobial peptides (AMPs) are autogenous polypeptides that are produced by multicellular organisms that protect the host by eliminating pathogenic microorganisms (Seo et al., 2012). They are host defence peptides as they are the key component for the innate immune system. AMPs target invasive and colonizing bacteria (Joo et al., 2016). Most AMPs that have been reported to date are characterized as four types, depending on their secondary structures; -sheet, extended, loop, and -helix. -sheet and -helix peptides are more common than extended, and loop. -helix peptides are the most studied peptides to date. (Bahar, et al, 2013). AMPs have typically 50 amino acids. (Seo et al., 2012). In the AMP data base, there are roughly 2,300 AMPs that have been reported (Park et al., 2011). The need to develop new antibiotic resistant drugs is urgent and is driving research for AMPs (Bahar et al., 2013). Due to the widespread use of antibiotics, the emergence of antibiotic resistant bacteria soon followed from the discovery of Penicillin in 1928 by Fleming (Park et al, 2011). This is due to the abuse and increasing use of antibiotics. Therefore, hospital patients are suffering from ‘superbugs’ such as, vancomycin resistant enterococci (VRE) and, methicillin resistant staphylococcus aureus (MRSA) all over the world (Park et al, 2011). Superbugs describes bacteria that is resistant to most antibiotics used commonly today (Mayo Foundation for Medical Education and Research. 2018). Natural AMPs are found in both eukaryotes e.g. fungi, insects, plants, protozoan, animals, and prokaryotes e.g. bacteria. Eukaryotic cells have several cells that are involved in the production of AMPs such as lymph’s, genitourinary systems, epithelial cells in gastrointestinal, phagocytes, and lymphocytes of the immune system (Bahar et al 2013). AMPs are interesting targets to be used as a substitute for antibiotics because they have a broad-spectrum activity, this includes antibiotic resistant bacteria. They also have considerable advantages for therapeutic use such as, the broad-spectrum activity, relatively low possibility of becoming resistant due to the general lipid bilayer structure makes it difficult to develop a whole resistance to AMPs (Bahar et al., 2013), and rapid onset of activity. (Seo et al., 2012). Since the discovery of AMPs from frogs and insects in the 1980s many other peptides have been identified and 2

1004BMS 1,200 have been isolated (Park et al., 2011). The structures and sequences of these peptides are varied but they do have other properties in common. These include: amphipathic secondary structures, within membranes, small size, a positive net charge within physiological conditions, rapid binding to the biological membranes, and the ability to kill the invading microorganisms within minutes (Park et al., 2011). It has recently become known that in mammals AMPs do not just fend off pathogens but they also shape the formation of the microbiome. This is important to maintain many aspects of health (Zhang et al., 2016).

Although research has been pushed for AMPs for a new antibiotic generation, that the knowledge and lead components of AMPS may enter more clinical tests in the future, the infection control may be hindered still. These reasons include, low specificity, manufacturer costs being high, lack of robust guidelines for rational design and potential toxicity to animal cells. (Bahar et al., 2013) There are problems with using AMPs as a therapy, peptides will only survive for a few hours within the body therefore taking this medicine orally is ineffective. The peptides would also break down when they get into the small intestine preventing the peptide from enter the blood stream. As peptides are absorb virtually none of the peptides within the small intestine of a mammal if the amino acid sequence is longer than four (Colorado State University, 2018) (React, 2017). For this reason, peptide drugs must be given intravenously or directly into the affected area (React, 2017). Thus, using AMPs for long periods of time will be difficult, due to lack of resources for domestic injections as they would need to be administered multiple times per day. Doing such injections at home would be considered a risk due to unsafe. Unsafe injection practices are quite common, especially in the developing world (Gupta et al., 2013).

Due to the problems associated with antibiotic resistant bacteria there is a need to produce new therapies. AMPs are a promising agent that could produce the new generation of antibiotics (Seo et al., 2012). Natural molecules like antibiotics are produced by most cells. They inhibit or directly kill the growth of a foreign microorganisms. It has recently become known that in mammals AMPs do not just fend off pathogens but they also shape the formation of the microbiome. This is important to maintain many aspects of health (Zhang et al., 2016). Although research has been pushed for AMPs for a new antibiotic generation, that the knowledge and 3

1004BMS lead components of AMPS may enter more clinical tests in the future, the infection control may be hindered still. These reasons include, low specificity, manufacturer costs being high, lack of robust guidelines for rational design and potential toxicity to animal cells. (Bahar et al., 2013)

References:

 Colorado State University. (2018) Absorption of Amino Acids and Peptides [Online] Available from [4 Feb 2019]

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Bahar, A., Ren, D. (2013) ‘Antimicrobial Peptides’ Pharmaceuticals [Online] 6, (12) 1543-1575.

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Davis, J., and Davis, D. (2010) ‘Origins and Evolution of Antibiotic Resistance’ Microbiology and Molecular Biology Reviews 74, (3) 417-433.

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Frieri, M., Kumar, K., Boutin, A. (2016) ‘Antibiotic Resistance’ Journal of Infection and Public Health 10, 369-378

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Joo, H., Fu, C., Otto, M. (2016) Bacterial Strategies of Resistance to Antimicrobial Peptides Philosophical Transactions [Online] 371 Available from [5 Feb 2019]

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Mayo Foundation for Medical Education and Research. (2018) What are superbugs and how can I protect myself? [Online] Available from [4 March 2019]

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National Health Service. (2016) Antibiotic Resistance [Online] Available from

[5 Feb 2019]

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Park, S., Park, Y., Hahm, K. (2011) ‘The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infection and Biofilm Formation’ International Journal of Molecular Sciences [Online] 12 (9) Available from [4 Feb 2019]

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React (2017) Could the use of Antimicrobial Peptides create resistance to ourselves? [Online] available from [27 Feb 2019]

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Seo, M., Won, H., Kim, J., Mishig-Ochir, T., Lee, B. ‘Antimicrobial Peptides for Therapeutic Applications: A Review’ Molecules [Online] 17 12276-12286

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Stuart, B., Levy, M.D. (2002) The Antibiotic Paradox United States of America: Perseus Publishing

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Gupta, E., Bajpai, M., Sharma, P., Shah, A., and Sarin, SK. (2013) ‘Unsafe Injection Practices: A Potential Weapon for the Outbreak of Blood Borne Viruses in the Community’ Annals of Medical and Health Sciences Research 3, (2) 177-181

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World Health Organization. (2018) Antibiotic Resistance [Online] Available from [5 Feb 2019]

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World Health Organization. (2014) ‘Antimicrobial Resistance: Global Report on Surveillance’ [Online] Available from

[5 Feb 2019]

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