Many antimicrobial peptides can be found in different species but among them a few can be isolated from the human. Among them, two are very much important and they are cathelicidins (LL-37) and defensins (alpha and beta).
3.1 Cathelicidin
Cathelicidins are varying in amino acid sequence, structure and size. They range in size from 12-80 amino acid residues and have a wide range of structure (Gennaro R, 2000). About 30 cathelicidin family members have been idenfied in mammalian species but LL-37 is the only one cathelicidin found in human. LL-37 which begins with two leucine residues at its N-terminus, and is 37 a residues long, with a molecular weight of 18 kDa (Gudmundsson GH, 1995). LL-37 is disordered in aqueous solution but can
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Moreover, it had been found that LL-37 gene expression is influenced by MEK 1/2 and p38 MAPK signaling pathways in A549 cells infected with Mycobacterium bovis bacillus Calmette-Guerin which is a tuberculosis vaccine mostly used in worldwide (Mendez-Samperio P, 2008). As an antiviral agent, LL-37 has been found to give local protection against HIV-1 infection by epithelial expression (Bergman P, 2007). It was found that the immunological response of this peptide has been changed in infected patients with papillomavirus (Conner K, 2002). As an antifungal agent, it is also active against Candida albicans. The activity is depending on the culture condition whether it will effective as a superficial barrier to the invasion (den Hertog AL, 2006) (Lopez-Garcia B, 2005). 3.2 Defensins:
Defensins are also small, cysteine-rich and cationic peptide which are consisting of 18-45 amino acids with 6-8 cysteine residues and they form disulfide bridges. Due to the differences in alignment of disulfide bond and molecular structure, two subclasses can be found in human. They are alpha defensins and beta defensins. Human alpha defensins are also called human neutrophil peptides and have four subtypes such as, HNP1, HNP2, HNP3 and HNP4 which are 29-35 amino acids long. First three subtypes
One environment where bacteria are regularly exposed to antibiotics is in large livestock operations, where producers very often treat their cows and other animals with drugs to prevent epidemics in the unsanitary and overcrowded conditions, which are common in the livestock industry. The simple reason for this is that in the short term it is cheaper to drug up the animals with antibiotics than to keep a clean living environment for them. Another big reason for these producers to drug up the animals is the fact that feeding antibiotics to the livestock makes for larger animals. The problem occurs when bacteria in these animals survive the bombardment of antibiotics, and some always do, the
Oral medications along with healthy eating and exercise is prescribed to patients who suffer from this disease. According to the National Institute of Diabetes and Digestive and Kidney Diseases (2017) most people start their treatment with metformin pills, which come in as a liquid form tablet. Metformin is an oral medication that helps decrease the amount of glucose a person absorbs after eating and it also helps decrease the amount of glucose the liver produces (MedlinePlus, 2017). It is vital to decrease the amount of glucose in the body so that the patient will not develop hyperglycemia. In addition, metformin increases the body’s response to insulin meaning that cell receptors can use insulin and control the amount of glucose in the body (MedlinePlus, 2017). Another medication that is prescribe is SGLT-2, which blocks glucose reabsorption in the kidneys (Diabetes.co.uk, 2017). Therefore, this can help the kidney
Fosfomycin trimethamine is a phosphoric acid agent used to treat UTIs caused by enteric bacteria. It works by inhibiting an enzyme needed for cell wall synthesis. Synercid used to treat Staphylococcus and Enterococcus infections. These infections often include endocarditis and surgical infections and they work by binding to the ribosomes. Daptomycin is a lipopeptide works against gram positive bacteria disrupting membrane functions. It is not used very often.
Antibiotic have been essential tools for fight against bacterial infections since the early 20th century. Antibiotics fall under different groups based on the method of treatment. There are basically 3 main groups of antibiotics based on their mechanism of action, i.e Cell wall Disruptive Antibiotics like beta lactams, Protein synthesis inhibitors and nucleic acid
As we seen in the mechanism of action all beta-lactam antibiotics, share a basic chemical structure that includes a three carbon, one nitrogen cyclic amine structure is known as the beta-lactam ring. Beta-lactam ring attached with a side chain having a variable group to the core structure of by a peptide bond. The variation of the side chain contributes to antibacterial activity.FDA has approved over 34 beta-lactam compounds as active ingredients in drugs for human use. Beta-lactam antibiotics have the following five classes:
Daum, Robert S. M.D., C.M.; Miller, Loren G. M.D., M.P.H.; Immergluck, Lilly M.D. etc. The New England Journal of Medicine. 2017;376:2545–2555
Beta-lactam antibiotics include Penicillins and Cephalosporins that contain a chemical structure called a beta lactam ring. This structure is capable of binding to the enzymes that crosslink peptidoglycans. Beta-lactams interfere with cross linking by binding to enzymes preventing bacterial cell wall synthesis.
The advent of penicillin forever changed the world of medicine at its discovery with its ability to treat diseases, deadly at the time, that are now considered commonplace and easily treatable. Penicillin was one of the greatest discoveries of the twentieth century, as antibiotics are one of the most highly prescribed drugs in the world today. Although its discovery is often described as serendipitous, the process by which it was cultivated was quite meticulous, and continued attention has been paid to penicillin's further development. It is because penicillin and its derivatives have played such a vital role in everyday medicine that it is such an important topic.
The discovery of Penicillin transformed the medicine world extremely. With the development of penicillin infections that were life threatening and frequently fatal for example, pneumonia which now could be purely treated with Penicillin.
Until the 1970s, many new antibiotics found that at first is still sensitive. The last new class of antibiotics discovered in the 1980s (Figure 2.1). After the 1980s increasingly difficult to find new antibiotics, to maintain the efficacy of existing antibiotics were necessary measures to minimize the increase and spread of resistance to antibiotics, while efforts to find and develop new methods of treatment of the infection is still continued.1,15
The treatment of disease with drugs involves many factors. The ability for drugs to reach the infected area is dependent on absorption, distribution, metabolism, and excretion. This ability is only made possible by transport mechanisms in barrier epithelia. Most drugs carry a positive or negative charge in the body, making them slightly polar and hydrophilic. This is important because it keeps the drugs from permeating across various membranes in the body. Due to these characteristics, our bodies need specialized transport elements to ensure the drug can do its job. The transporters allow certain charged molecules to get through barrier membranes, and are thought to be involved with detoxification and drug
Dr. H. Scott Hurd author of, “The Other Side of Antimicrobial Resistance” is writing to contradict thought that antibiotic-resistance is becoming a complete global threat. (2012) the article gives several counter claims that lead you in a different mindset than simply healthcare precautions. The author talks about foodborne illness being linked to antibiotics resistance in modern medicine, also about the important knowledge that can be taken away from antibiotics when researching HIV/AIDS, Methicillin-Resistant Staphylococcus Aureus (MRSA), and hospital-acquired infections through research and development. The author is showing the readers that there is another side, such as, not needing to be concerned about resistance to any antibiotics because scientist and others have an understanding of certain guidelines when it comes to the patients’ health. Therefore, each excuse people are giving to support the claim antibiotic-resistance is a threat to people. He states in his writing, “As soon as an antibiotic is first used, resistance begins to develop.” He is wanting to imply in his message that even though over-prescribing is a big factor, even as simple as the first time an antibiotic is prescribed it is having effects on the patient. However, according to the Mayo Clinic, in “Antibiotics: Misuse puts you and others at risk” infers the overuse or misuse of antibacterial drugs can make resistance develop even faster, causing an epidemic before scientist can find a solution.
While we have made tremendous advancement in various fields of therapeutics, the triumph of Fleming’s discovery of penicillin is fading away with the rise of antibiotic resistance; we are pushing ourselves back into the pre-antibiotic era. In the United States 2 million people get infected with antibiotic resistant bacteria and 23,000 die each year as a result (CDC). The picture is grimmer in the developing world. This project was initiated to study a new avenue in the search of novel antimicrobials against bacteria.
Small molecules are the low molecular weight organic compounds having capacity to inhibit the growth of bacteria or their virulence potential. Previously, antibiotics were used for these purposes but today we need to be curious before using antibiotics due to the developing resistance. If antibiotics develop resistance, they are no longer effective for prevention, treatment or control of diseases caused by infectious microorganisms. Researchers are now exploring the new strategies and new compounds that can take the advantageous place in front of antibiotics. Use of probiotics, vaccine, herbal extracts are some of the new strategies. On the way of discovery and research, scientists are now
To begin with, I truly believe that the researchers, who have devoted their lives into studying the dynamics of drug interactions for the purpose of enhancing microbial eradication, are heroes in their own right. They have abide to do something with all their heart and soul for the better of mankind. We are living in an age where commitment is often, obscured by day to day life. Individuals make goals, often in the pursuit of glory, but Muhammad Ali once told us that goals, not written down, are only dreams. One can dream all we like but without commitment, nothing can be achieved.