Natural Products in the Fight Against Multi-Drug-Resistant Bacteria: Natural Antibiotics and Resistance

Natural Products in the Fight Against Multi-Drug-Resistant Bacteria: Natural Antibiotics and Resistance

Mümtaz Güran (Eastern Mediterranean University, Turkey)
DOI: 10.4018/978-1-7998-0307-2.ch007
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Abstract

It is well recognised that the antimicrobial resistance crisis has approached critical levels, and current treatment options are very limited, especially in the treatment of infections caused by resistant bacteria. Thus, ongoing research is focused on the development of new molecules which have broader antimicrobial activity. However, the advancements in drug development studies using synthetic compounds has led to a lack of success. Also, economic and regulatory issues have formed a challenge as well. Therefore, research has focused again on natural products. A large number of natural products and natural product-derived compounds are still in various stages of clinical development. Here, current research on the potential uses of natural products or their templates as viable sources of new drug candidates have been discussed to construct an understanding towards the goal of development of new antimicrobials to overcome resistant pathogens.
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Introduction

The life before antibiotics was dark and the discovery of antibiotics has shined upon the darkness of humanity and saved many lives. Average lifespan of a human being has increased significantly after the introduction of antibiotics. But, after a century of gains in the war against infectious diseases, the humanity is losing ground again. Common bacteria, parasites and fungi are developing widespread immunity to our best weapons.

Since its development, the humanity thought that penicillin will be a magic bullet for the infectious diseases. It has been used extensively and irresponsibly together with other following antimicrobials. Since many decades, there is a tremendous effort throughout the world to overcome the global antibiotic resistance. But now, medical authorities are raising concerns that treatment options in certain infectious diseases are narrowing because of alarming global antibiotic resistance problem. As new antimicrobial drugs are developing, the need for newer ones grow as well.

The looming public health crisis of antimicrobial-resistance have been evaluated by Centers for Disease Control and Prevention (CDC) and a report on antimicrobial resistance and its impact on various sectors in United States of America (USA) which highlights the scope of the problem have been published (CDC, 2013). CDC estimates that in the United States, more than two million people are infected every year with antibiotic-resistant bacteria, ending with at least 23,000 deaths as a result. From an economic standpoint, an economic burden of $18,000 -- 29,000 of medical costs per patient in a single year have been reported for USA in the year of 2000 which is similar in many geographies (Thabit et al., 2015). For example, high burden of antimicrobial drug resistance in Asia have been reported for various pathogens, namely; Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin Resistant S. aureus (VISA), Vancomycin resistant Enterococcus (VRE), macrolide and penicillin resistant Streptococcus pneumoniae, Extended Spectrum Beta- Lactamase Producer Escherichia coli and Klebsiella pneumoniae, Carbapenem Resistant Enterococci (CRE), Multi drug resistant (MDR) Pseudomonas aeruginosa and Acinetobacter spp. are mentioned as superbugs of the 21st century (Lai et al., 2014).

As a result, the emergence of pathogens with different mechanisms of resistance has intensified the challenges associated with infection control and treatment strategies. Therefore, as prudent use of antimicrobials is not at the intended level, development of novel antimicrobial molecules remains as the main strategy to overcome the present narrow pass. In this context, many products have been studied to develop antimicrobials and the major sources of chemical diversity for starting materials were mainly natural products because of their abundant scaffold diversity (Mishra & Tiwari, 2011). Before, the pharmaceutical companies were using crude plant extracts to produce relatively simple therapeutic formulations but nowadays purified compounds and their chemically modified derivates have been included in many drug formulations. Despite there are plenty of possibilities coming from pure natural compounds, sometimes modification of formulations of natural compounds can be an option in developing antimicrobial molecules too. On the other hand, discovery of antimicrobial effectiveness of a molecule is not enough to use it as a therapeutic agent. For this, a drug approval process has to be carried out. To register a novel molecule as a drug, an Investigational New Drug (IND) application must be submitted to the Food and Drug Administration (FDA) in USA or European Medicines Agency (EMA) in Europe. Afterwards, the process continues with successful clinical trials ending with another application for marketing licenses namely, New Drug Application (NDA) in the USA or a Marketing Authorization Application (MAA) in Europe. This though period rarely ends with the introduction of novel, safe antimicrobials into the market. Nevertheless, many natural products and derived compounds are still in various stages of clinical development. So, the use of natural products or their templates is a viable source of new drug candidates.

Here, various natural products and their applications have been discussed to construct an understanding towards the goal of development of new strategies to overcome infectious diseases caused by antimicrobial resistant bacteria.

Key Terms in this Chapter

Infection: An invasion of an organism by a pathogen such as bacteria or viruses, often causing an immune response from the host. Some infections lead to disease.

Pathogens: Bacteria, viruses, parasites, or fungi that can cause disease.

Adverse Effects: When medical drugs, like antibiotics, have harmful or distracting effects on person being used or applied.

Antimicrobial: Any substance (including an antibiotic) used to kill or inhibit the growth of bacteria, viruses, fungi, or parasites. This term is a non-specific one which is a wider term than antibiotic.

Natural Product: Substances, compounds or molecules isolated from natural sources.

Antibiotic: Class of substances that can kill or inhibit the growth of some groups of microorganisms. Despite being a wide term, herein the word antibiotic resembles a drug that kills or stops the growth of bacteria particularly. Examples include penicillin and streptomycin.

Antimicrobial Resistance: The ability of a microbe to survive and continue to multiply during and after the encounter with a certain antimicrobial agent. Antimicrobial resistance includes antibiotic, antibacterial, antifungal, and antiviral resistance.

Antifungal: Class of substances that can kill or inhibit the growth of fungi.

Antibacterial: Class of substances that can kill or inhibit the growth of bacteria.

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