Recent Trends and The Future of Antimicrobial Agents - Part 2

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder currently plaguing women. There are many factors associated with high androgenicity in the female body. Dysbiosis of gut microbiota may be one of the primary reasons that initiate PCOS. Emerging evidence suggests that some plastics, pesticides, synthetic fertilizers, electronic waste, food additives, and artificial hormones that release endocrine-disrupting chemicals (EDCs) cause microbial Dysbiosis. It is reported that the permeability of the gut is increased due to an increase of some Gram-negative bacteria. It helps to promote the lipopolysaccharides (LPS) from the gut lumen to enter the systemic circulation resulting in inflammation. Due to inflammation, insulin receptors' impaired activity may result in insulin resistance (IR), which could be a possible pathogenic factor in PCOS development. Good bacteria produce short-chain fatty acids (SCFAs), and these SCFAs have been reported to increase the development of Mucin-2 (MUC-2) mucin in colonic mucosal cells and prevent the passage of bacteria. Probiotic supplementation for PCOS patients enhances many biochemical pathways with beneficial effects on changing the colonic bacterial balance. This way of applying probiotics in the modulation of the gut microbiome could be a potential therapy for PCOS.

In the 1890s, Behring and Kitasato established the principle of serum therapy, which proved useful in treating infectious diseases. However, by the 1940s, serum therapy was abandoned mainly due to complications associated with the toxicity of heterologous sera and the introduction of more effective antibiotics. Although the availability of antibiotics had a tremendous impact on saving lives from infectious diseases, there was a rapid emergence of antibiotic resistance. As a result, an alternative therapy is being given due consideration. With the advent of antibody production technology, antibody therapy has gained interest as a promising treatment for emerging infectious diseases. Some monoclonal antibodies (mAbs) had already been approved for the treatment of certain infectious diseases. Many mAb candidates are currently in different phases of clinical testing for a variety of infectious pathogens. There is hope that antibody therapy may appear as a promising treatment option against infectious diseases in the near future. 

Numerous antimicrobial peptides (AMP) obtained from natural sources are currently tested in clinical or preclinical settings for treating infections triggered by antimicrobial-resistant bacteria. Several experiments with cyclic, linear and diastereomeric AMPs have proved that the geometry, along with the chemical properties of an AMP, is important for the microbiological activities of these compounds. It is understood that the combination of the hydrophobic and hydrophilic nature of AMPs is crucial for the adsorption and destruction of the bacterial membrane. However, the application of AMPs in therapeutics is still limited due to their poor pharmacokinetics, low bacteriological efficacy and overall high manufacturing costs. To overcome these problems, a variety of newly synthesized cationic amphiphiles have recently appeared, which imitate not only the amphiphilic nature but also the potent antibacterial activities of the AMPs with better pharmacokinetic properties and lesser in vitro toxicity. Thus, amphiphiles of this new genre have enough potential to deliver several antibacterial molecules in years to come.

The emergence and expansion of antibiotic resistance in pathogenic bacteria have become a global threat to both humans and animals. Immense use, overuse and misuse of antibiotics over several decades have increased the frequencies of resistance in pathogenic bacteria and resulted in significant medical problems. To fight against the widespread drug-resistant pathogenic bacteria has become a terrific challenge for the modern healthcare system. The major challenges to fight against pathogenic bacteria involve long-term antibiotic therapy with combinations of drugs. The abundance of resistance mechanisms in pathogenic bacteria has compelled many therapeutic antibiotics to become ineffective. As a result, the elimination of drug-resistant pathogenic bacteria requires a judicious strategy. The advent of nanotechnology has unveiled a new horizon in the field of nanomedicine. Nanoparticle-based techniques have the potential to overcome the challenges faced by traditional antimicrobials. In this way, self-assembling amphiphilic molecules have emerged as a fascinating technique to fight against pathogenic bacteria because of their ability to function as nanocarriers of bactericidal agents and interact and disrupt bacterial membranes. Nanocarrier-based drug delivery systems can mitigate toxicity issues and the adverse effects of high antibiotic doses. The focus of this chapter is to discuss various amphiphilic nanocarriers and their roles and possibilities in fighting against pathogenic bacteria. 

Schiff base ligands or compounds are useful in modern inorganic chemistry. Numerous transition metal-based catalysts have been synthesized with Schiff base scaffolds. The application of such Schiff bases is also found in biological studies. Herein, we have discussed the various synthetic procedures of diversified Schiff base compounds and their metal complexes. The biological activity of those complexes has also been delineated in this chapter with special emphasis. Various metal complexes [Co(II), Ni(II), Cu(II), Zn(II) and Fe(III)] with different Schiff base compounds displayed anti-fungal activity. Similarly, anti-viral activity was seen with Co(II) and Pd(II) metal complexes. Many Schiff base-metal complexes are found, which showed anti-cancer activity against various carcinoma cells like HpG2, MCF-7, A549, HCT116, Caco-2 and PC-3. Similarly, the transition metal complexes (generally 1st and 2 nd row) of Schiff bases also exhibited good anti-bacterial activity against various bacterial strains. The ionic-liquid-tagged Schiff bases have also been found to be good anti-microbial agents

Metal-Organic Frameworks (MOFs) are a class of porous crystalline materials made-up of transition-metal cations linked with multidentate organic ligands by the coordination bonds. The strong, flexible frameworks and the porous structure of the MOFs establish them as an effective carriers of various functional compounds, such as gases, drugs, and anti-microbial agents. The MOFs render high loading capacity and sustained release, which is the desired property in anti-microbial applications. Similar porous material for the anti-microbial application is Zeolite, however, it is more complex to synthesize than MOFs. Currently, MOFs are used mainly in catalysis, gas separation and storage, and water purification applications. In the applications as anti-microbial agents, MOFs are just emerging into the field application from the laboratory scale. Hence, this chapter discusses the properties, synthetic procedures, anti-bacterial mechanisms and various forms of MOFs for anti-microbial applications. The MOFs are often doped with metal nanoparticles, polymers, and metal-polymer complexes. Each category of MOFs has a different mechanistic approach to inhibiting microbial colony growth. In this regard, this chapter will provide sufficient information on the MOFs, which will help to understand their significance in anti-microbial applications and their scope

The natural environment acts as the largest ‘bio-laboratory” of yeast, algae, fungi, plants etc., which are used as an abundant source of biomolecules. These different biomolecules play vital roles in the formation of different biogenic metals or metalloid nanoparticles. Recently, the overburden from the different microbial diseases has increased rapidly in different application sectors, viz., drug delivery, DNA analysis, cancer treatment, antimicrobial agents, water treatment and biosensor and catalysts, as a result of multipurpose work occurrence globally. The indiscriminate and arbitrary use of antibiotics in clinical practice has spurred the emergence of potentially lifethreatening multidrug-resistant pathogens. In the quest for novel antimicrobial agents, the current interest is to develop potent antimicrobial agents which exhibit broadspectrum bactericidal activity and possess a mechanism of action that does not readily favor the development of resistance. The use of nanoscale materials as bactericidal agents represents a novel paradigm in antibacterial therapeutics. Actually, eco-friendly, sustainable modern approaches, such as green syntheses of different biogenic metals or metalloid nanoparticles, are cost-effective and environment-friendly, and they are used as strong antimicrobial agents. This chapter focuses on synthesizing biogenic metal or metalloid nanoparticles with special emphasis on microbial synthesis, particularly from yeast, bacteria, algae, fungi, plants extract, etc. Finally, a detailed description of the biosynthesis mechanism using different green sources, along with their antimicrobial activity and mode of action, has been presented. 

The development of resistance against antibiotics in microorganisms has led to the search for alternatives that can effectively kill microbes and will have a lesser probability of the generation of resistance. In this regard, nanomaterials have emerged as protagonists demonstrating efficient antibacterial activities against drug-resistant strains. Amongst nanomaterials, 2D nanosheets have attracted attention as an antibacterial agent due to their sheet-like features, having sharp edges and corners which can pierce through bacterial membranes, subsequently leading to membrane damage. The present chapter discusses the antibacterial potential of one such 2D material, transition metal dichalcogenides, specifically MoS2 nanosheets and their composites. A brief discussion about the synthesis of MoS2 nanosheets is presented, and a detailed overview of its application as an antibacterial agent is illustrated. The mechanism of action of antibacterial activity of 2D MoS2 nanosheets is discussed, which shows that these nanosheets can cause bacterial cell death through membrane damage and depolarization, metabolic inactivation and generation of reactive oxygen species (ROS). Further, the photothermal property and the intrinsic peroxidase-like activity in certain conditions can also show antibacterial activity, which is summarized in the chapter along with the biocompatibility evaluation. 

The emergence of antibiotic-resistant bacteria poses a critical public health issue worldwide, which demands the development of novel therapeutic agents as viable alternatives to antibiotics. The advent of nanoscience and technology offers the synthesis of several potential anti-microbial agents that are effective against both Gram-positive and Gram-negative bacterial strains. One such nanoscale material that fascinated researchers due to its unique optoelectronic properties is Quantum Dots (QDs). Moreover, these are found to be highly bactericidal, even against resistant bacterial infections. Thus, a significant number of researches have been going on globally to employ QDs as potent bactericidal agents alone or in combination with antibiotics. Studies demonstrated that intracellular uptakes of QDs elevate the level of reactive oxygen species (ROS) inside the cells, which turns-on cascades of intracellular events that cause damage to DNA and proteins. However, the inherent reactive nature of these metallic and semiconductor QDs raises huge concern for translational research as these are found to be cytotoxic and non-biocompatible. Moreover, the human body does not have a proper sequester mechanism to remove these metallic ions from the body, which limits its direct applications. Recent progress in this line of interest has focused on developing non-metallic quantum dots, such as carbon dots (CQDs) and Black Phosphorus quantum dots (BP QDs) which showed less toxicity and immunogenicity suitable for real-life applications. Therefore, in the present chapter, we are going to discuss the recent development of bactericidal QDs and various types of surface functionalization illustrated recently to increase biocompatibility.

Antimicrobial photodynamic therapy (aPDT) is a new-age therapeutic technique that by principle, focuses on the eradication of target cells by highly cytotoxic reactive oxygen species (ROS) generated through the activation of a chemical photosensitizer (PS) molecule with visible light of appropriate wavelength. The cytotoxic species can arise via two main mechanisms known as Type I and Type II photoreactions: the former leads to the generation of ROS and the latter to the formation of the singlet oxygen. These highly reactive oxidants can bring about instantaneous oxidation of a great array of biological molecules, causing havoc to the target cell. This technique provides significant advantages over conventional antimicrobial therapies in practice which are now facing the burning threat of growing complete resistance against them. To combat this world-wide health concern, new treatment strategies are the need of the time while ensuring no further rise of resistance against those alternative therapies, and aPDT appears to be highly promising in this aspect by fulfilling all the demands at the same time. It appears not only equally effective at killing both antibiotic-sensitive and multi-resistant bacterial strains, but also highly selective, non-invasive and rapid in action than other antimicrobial agents, and there have been no reports of resistance till date. The success of this phototherapy relies on several factors, including the target cell type, reaction conditions, and the type, molecular structure and cytolocalization of the PS; because its potency depends on the distribution, high reactivity and short lifetime of ROS as well as the PS itself in electronically excited states.