Lipopeptides as Antimicrobials: Applications and mechanisms to Treat Drug Resistant Pathogens.
Alex Harris
10/05/2015
First Draft
Cell Biology
CELL 7990-01
Dr. Robert Dotson
1. Abstract
A. Drug resistant pathogen diseases are increasing
B. Lipopeptides, with their amphipathic structure can target cell membrane
C. Used currently as antibiotics and antifungals.
i. Similar mechanisms of action for antibiotic properties ii. Separate similar mechanisms for antifungal properties
D. This paper describes their development, mechanisms, and applications in medicine.
2. Introduction
A. Global Impact
Over the past century, global demands for new medicines and materials have increased.
Recently, many antimicrobial resistant organisms have emerged. These microbes have become less treatable with current medications and make it difficult to prevent or treat infections in patients. Higher doses of medicine are used, but may lead to drastic side effects. Staphylococcus aureus has recently developed resistances to multiple drugs, including penicillin, methicillin, tetracyclin, and even vancomycin. The World Health Organization reported in April 2014 that drug resistant microorganisms are “…no longer a prediction for the future, it is happening right now…” New drugs are required to treat patients with these drug resistant infections.
1. Chemical cleanup
2. Renewable resources are an advantage ii. Use as antimicrobial
1. Novel antibiotics discovered at a high rate in
Methicillin-resistant Staphylococcus aureus, or more commonly, MRSA, is an emerging infectious disease affecting many people worldwide. MRSA, in particular, is a very interesting disease because although many people can be carriers of it, it generally only affects those with a depressed immune system; this is why it is so prevalent in places like nursing homes and hospitals. It can be spread though surgeries, artificial joints, tubing, and skin-to-skin contact. Although there is not one specific treatment of this disease, there are ways to test what antibiotics work best and sometimes antibiotics aren’t even necessary.
With all of our modern advances, it seems somewhat strange that chronic health problems have become so commonplace. When antibiotics were discovered, they predicted the end of disease. Instead, we now have a world full of frightening antibiotic resistant infections.
When penicillin was released to the public in 1944, it was a miracle drug. Infections that had been killers were suddenly treatable. Doctors recommended it generously, both for illnesses that needed it and illnesses that didn’t. Before long, however, it took much stronger doses to see penicillin’s effects. When the antibiotic arms race began in 1944, most physicians assumed that new antibiotics would be discovered or created to keep up with the evolving resistance in bacteria, but the bacteria are constantly evolving new defenses and doctors are starting to run low on antibiotic ammunition. MRSA, methicillin-resistant Staphylococcus aureus, is one of many types of bacteria
Before the turn of the 21st century, physicians across the country were realizing that the possibility of being able to treat and cure virtually any microbial infection with the use of a single or a combination of antimicrobial medications was becoming more and more of a challenge. In the late 1960s and early 1970s, reports of pathogenic resistance to even the most potent antimicrobial medications of the time were being sent to the Centers for Disease Control. Among even the most dangerous pathogens that have developed and are developing drug resistance to one or many antimicrobials, Staphylococcus aureus (S. aureus) is perhaps a case in which the world is most familiar and of the greatest concern within the medical community due to its natural virulence-its ability to cause a multitude of life-threatening infections, and its above average ability to combat and adapt to a vast array of environmental conditions.
Methicillin resistant Staphylococcus aureus (MRSA) has been a type of multidrug resistant organism and staph bacteria known to cause serious infection that can lead to long hospitalizations and death. It can begin as a simple infection on skin or in the lungs, and if left untreated, can lead to traveling to the bloodstream and causing sepsis (“Methicillin-resistant Staphylococcus aureus (MRSA), 2015”). The Centers for Disease Control and Prevention reports that 33 percent of individuals carry the staph bacteria intranasally and two percent of individuals carry MRSA (“Methicillin-resistant Staphylococcus aureus (MRSA), 2015”). Even though this is a serious issue among healthcare settings all over the country, the number of people affected
Widespread use of antibiotics has been very controversial in the media as well in the general population. Due to these controversies, it is very misunderstood to how antibiotics work leading to many patients in the hospital setting wanting to take them when it is not necessary or refusing to take when it is necessary for their survival. Some of this controversy is due to antibiotic resistance, which has spread an alarming rate in the 21st century (Walsh, 2000). Antibiotic resistance is the result of very strong bacteria or microbes that are resistant to the antibiotic prescribed and those microbes accumulate overtime by their survival, reproduction and transfer, leading to increased levels of antibiotic resistance.
Staphylococcus aureus is a leading cause of human bacterial infections worldwide1, and following the discovery and widespread utilization of antibiotics, S. aureus has evolved to become resistant to a number of antimicrobial treatments. Most notably, Methicillin-resistant Staphylococcus aureus (MRSA) strains have acquired the mecA gene, encoding the penicillin binding protein (PBP2a), which confers resistance to oxacillin and all β-lactam antibiotics 2. These characteristics, combined with other virulence factors, have made MRSA infections difficult to treat, and lead to MRSA being recognized as a significant cause of morbidity and mortality 3. MRSA is also the leading cause of nosocomial infections4–6, contributing significantly to increased healthcare costs 7. CDC estimated in 2008 that MRSA was responsible for 89,785 cases of disease, causing 15,249 deaths in the US8.
When Penicillin was first introduced in the early 1940’s to treat bacterial infection, resistance strains of Staphylococcus Aureus were completely unidentified. However, only a decade later, the disease was already becoming very common in hospital environments. Because of this, Methicillin was introduced in 1961 to medicate these resistance strains, yet within a single year, doctors were already encountering Methicillin-Resistant Staphylococcus
Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogen that causes many complicated health infections in our body. It’s a type of s. aureus bacteria that can produced by process of resistance to many antibiotics such as dicloxacillin, oxacillin, and methicillin. Why is MRSA so dangerous? Its natural ability is to continue transforming in ways to prevent from antibiotic from being completely successful in the batter against MRSA. The US had spent billions of dollar every year into research in order to prevent it from further spreading. In order to do so, we must step up to advance our technology and knowledge to be able to defeat the bacterial warfare. This research will discuss the prevalence and different factors of the disease, it
According to the Centers for Disease Control and Prevention (as cited in Upshaw-Owens & Bailey, 2012) MRSA-related infections have risen from 2% of S.aureus infections in 1974 to 64% in 2004. In the United States 46% of S.aureus cases are Methicillin resistant. The rise in infection rates is alarming and
In the past tense 60 years, antibiotic drugs have been critical to the fight against infectious disease caused by bacteria and other microbe. Antimicrobial chemotherapy has been a lead cause for the dramatic rise of norm life expectancy in the Twentieth Century. 1 However, disease-causing bug that have become resistant to antibiotic drug therapy are an increasing public health trouble. “Wound contagion, tuberculosis, pneumonia, gonorrhea, childhood ear infections, and septicemia are just a few of the diseases that have become hard to treat with antibiotics.” 2 One part of the job is that bacteria and other germ that cause infections are remarkably resilient and have developed several ways to resist antibiotics and other antimicrobial drug. 3 Another part of the problem is due to increasing use, and abuse, of existing
Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are resistant to all beta-lactam antibiotics such as methicillin, penicillin, oxacillin, and amoxicillin. Sometimes called a “super-bug” because of its ability to resist so many of our antibiotics. MRSA can be fatal and according to the CDC, of the over 80,000 invasive MRSA infections every year, 11,285 related deaths occur. Methicillin-resistant Staphylococcus aureus (MRSA) has become the bacteria of this decade.
The occurrence of multidrug-resistant (MDR) pathogens has gradually become a cause for serious concern that impends the effective prevention and treatment with regard to nosocomial infections. With this alarming cases, the World Health Organization (WHO) has recently identified antimicrobial resistance as an increasingly serious threat to global public health that requires action across all government sectors and society (Bassetti, Ginocchio, & Mikulska M, 2011). The most common and serious MDR pathogens have been comprehended within the acronym “ESKAPE,” – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. (Howard, O'Donoghue, Feeney, & Sleator, 2012).
Take for example MRSA (Methicillin-resistant Staphylococcus aureus), a S. aureus strain that was discovered in 1961 to be resistant to the antibiotic methicillin. Webmd indicates that MRSA has now grown its resistance from methicillin to “amoxicillin, penicillin, oxacillin and many other common antibiotics” (MRSA). This increase in resistance of a methicillin-resistant strain of S. aureus can be attributed to the increasing use and overuse of antibiotics, not only in the doctor’s office but also in agriculture. MRSA is only one of many antibiotic resistant strains of bacteria. New resistant strains are evolving rapidly. According to Dr. Ed Warren, “there are high levels of antibiotic resistance in bacteria causing common infections (e.g. urinary tract infections, pneumonia, bloodstream infections) in all regions of the world” (21).
Platensimycin (PTM), a metabolite of Streptomyces platensis, is an exceptional example of a distinctive structural class of natural antibiotics and have been shown to be a breakthrough in current antibiotic research due to its characteristic functional pattern and important antibacterial activity. PTM mode of action is not exploited by current drugs which makes it an important antibiotic lead against antibiotic resistance. PTM is a potent and selective inhibitors of bacterial fatty acid synthesis and targets β-ketoacyl-acyl carrier protein (ACP) synthase I/II, FabF/B elongation. It has a potent broad-spectrum Gram-positive activity in vitro and exhibits no cross-resistance to other key antibiotic-resistance bacteria including Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus, vancomycin-resistantEnterococci and linezolid-resistant, macrolide-resistant pathogens and demonstrates no cross-resistance with other antibiotics. Plantensimycin proved effective in clearing methicillin-resistant S. aureus infection from a mouse model in vitro although the high doses and suboptimal delivery system require further modification of its structure before conducting clinical trials.