Antibiotics

Since the accidental discovery of penicillin by Alexander Fleming in 1929, there have been several kinds of antibiotics available in the market, effective against a wide variety of bacterial pathogens. These antibiotics have different modes of action, affecting either cell wall synthesis, protein synthesis or nucleic acid synthesis. Although considered magic bullets at one point in time, many of the commonly used antibiotics are now ineffective against certain pathogens. This is due to the development of antibiotic resistance among such pathogens, owing to the indiscriminate usage of antibiotics across different settings. This article attempts to explore the nature of antibiotics, their mode of action, and the phenomenon of antibiotic resistance among bacteria.

What are Antibiotics?

Microorganisms, especially bacteria, cause some deadly infections in humans and other animals. Hence, their control becomes imperative. The term antibiotic means “against life”. In this sense, antibiotics are defined as drugs that inhibit the growth of living organisms, particularly bacteria. Antibiotics are antibacterial chemical substances produced by many strains of fungi and bacteria, in their natural settings, as a defence mechanism. These substances have been exploited to act against the pathogenic bacteria that infect humans and other animals. Such substances are known to either kill or slow down the growth of pathogenic bacteria, therefore holding great medical significance.

Although most antibiotics are derived naturally, many of the antibiotics these days are chemical derivatives of naturally occurring antimicrobial chemicals. For example, Penicillin G has been used to synthesise various other penicillins.

Uses of Antibiotics

Antibiotics are used in a variety of different settings including.

• In hospitals and treatment facilities to treat diseases and prevent bacterial infections after surgeries.

• Usage in food production-livestock is treated to promote growth and disease resistance.

• Crops and trees are treated to prevent the development of bacterial infections.

• Aquaculture.

  Interestingly, almost 60% of the antibiotics manufactured are used in agriculture.

Types of Antibiotics

• Based on their effects on the bacteria, antibiotics may be bactericidal (kill the bacteria) or bacteriostatic (inhibit growth and reproduction).

• An antibiotic may be broad-spectrum or narrow-spectrum, depending on the susceptibility of different groups of bacteria to them. A narrow-spectrum antibiotic is only effective against gram-positive bacteria or gram-negative bacteria. On the other hand, broad-spectrum antibiotics work well against both groups.

• Based on their nature, i.e., natural or synthetic −.

1. Natural Antibiotics	I. Bacterial 1. Streptomyces: Streptomyces, Amphotericin B, Kanamycin, Neomycin, Chloramphenicol 2. Micromonospora: Gentamicin 3. Bacillus: Bacitracin II. Fungal 1. Penicillium: Penicillin-G, Griseofulvin  2. Cephalosporium: Cephalosporins
2. Synthetic Antibiotics	Manufactured under lab settings Examples: Sulfonamides,  Chloramphenicol,  Ciprofloxacin,  Trimethoprim,  Isoniazid,   Dapsone, etc.
3. Semisynthetic Antibiotics	Derived from natural sources, modified by adding chemical groups Examples:  Ampicillin, Methicillin, Carbenicillin, etc, derived from Penicillin-G

• Antibiotics can be grouped based on their mode of action, as follows −.

S.No	Mode of action	Examples of antibiotics
1	Inhibition of cell wall synthesis (disruption of peptidoglycan synthesis)	Penicillins, Cephalosporins, Vancomycin, and their derivatives
2	Disruption of cell membrane (by pore formation in the cell membrane)	Polymyxins, Daptomycin, etc.
3	Inhibition of protein synthesis (by chain termination or total inhibition of synthesis)	Aminoglycosides, Tetracyclines, Macrolides, Chloramphenicol, etc
4	Inhibition of DNA synthesis	Quinolones and Fluoroquinolones, Rifampicin
5	Inhibition of RNA synthesis	Rifampin, Actinomycin
6	Antimetabolites (mostly by targeting folic acid synthesis)	Sulfonamides, Isoniazid, Dapsone, Trimethoprim

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Examples of Antibiotics

Antibiotics are often classified based on their structural composition. On this basis, we have the following examples &inus;.

• 𝛃-lactams− Cephalosporins, Penicillins, etc.

• Aminoglycosides− Streptomycin, Kanamycin, Gentamicin, etc.

• Tetracyclines− Tetracycline, Doxycycline, etc.

• Macrolides− Erythromycin, Azithromycin, etc.

• Quinolones− Nalidixic Acid, Ciprofloxacin, etc.

• Sulfa drugs− Sulfanilamide, Sulfamethoxazole, etc.

• Polypeptides− Vancomycin, Bacitracin, etc.

Role of Antibodies in Antibiotics

Antibodies are proteins produced by the immune system in response to a pathogenic invasion. Antibiotic drugs are known to immunomodulate the host's defences against the pathogen. Immunomodulation refers to the triggering of the immune system of the host, against the pathogen, by the antibiotic. Hence, antibiotics are found to have a positive effect on the activity of antibodies. Immunocompromised patients have shown that the recovery of an individual is dependent on the joint action of antibodies and antibiotics.

Antibiotics can modify the bacterial structure and expose the epitopes of the antigen, thereby easing the action of antibodies. Moreover, antibiotics may help reduce or inhibit the expression of certain virulent genes that would otherwise supress the immune response. Hence, antibiotocs, coupled with antibodies help reduce the inflammation response caused by the immune system. In recent researches, an Antibody-Antibiotic Conjugate (AAC) has shown its action against pathogenic bacteria, being efficient against Staphylococcus aureus infections.

What is Antibiotic Resistance?

Antibiotic resistance refers to the ability of bacteria to survive (resist) the effects of antibiotics used against them. Such bacterial cells that are not killed or affected by an antibiotic are referred to as antibiotic-resistant bacteria. Bacteria are subject to selective pressure exerted by antibiotics present in the environment which promotes the survivability and multiplication of the resistant type species while the susceptible ones are eliminatedAntibiotic resistance refers to the ability of bacteria to survive (resist) the effects of antibiotics used against them. Such bacterial cells that are not killed or affected by an antibiotic are referred to as antibiotic-resistant bacteria. Bacteria are subject to selective pressure exerted by antibiotics present in the environment which promotes the survivability and multiplication of the resistant type species while the susceptible ones are eliminated.

Reasons for antibiotic resistance among bacteria include but are not limited to.

• The indiscriminate usage of antibiotics, including rampant prescriptions and self-diagnoses of the patients.

• Inappropriate prescriptions, such as prescribing antibiotics for viral infections.

• Failure to complete the full course of antibiotics, leads to the survival of resistant forms.

• Non-therapeutic usage of antibiotics in livestock feeds as growth enhancers.

• The horizontal transfer of antibiotic resistance genes among bacteria of the same species and different species.

Antibiotics work by targeting the cell wall synthesis, the protein synthesis, or the DNA replication processes of the bacterial target cell. However, random mutations in the chromosomes of the bacteria and selection pressure can lead to the development of resistance mechanisms. There are four major mechanisms through which antibiotic resistance is conferred to the bacteria.

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• Inactivation of the drug by destruction (e.g., hydrolysis of the 𝛃-lactam ring of penicillins by penicillinases).

• Modification or altered metabolic pathway of the drug target in the bacterial cell (e.g. increased folate production to counter sulfonamide inhibition).

• Prevention of the antimicrobial from reaching the target, via reduced cell permeability or by metabolic bypasses (e.g. Penicillin-G resistance in gram-negative bacteria).

• Expulsion of the antimicrobial agent through efflux pumps (e.g. Tetracycline resistance in E. coli, S. aureus).

These mechanisms are encoded within genes known as antibiotic resistance genes (ARGs). These genes can be transferred from one group of bacteria to another, via horizontal gene transfers. The transfers can also occur between two different species of bacteria. This transfer of resistance genes is instrumental in the widespread occurrence of antibiotic resistance.

Examples of antibiotic-resistant bacteria −

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• Methicillin-Resistant Staphylococcus aureus (MRSA).

• Vancomycin-resistant Enterococcus faecium (VRE).

• Vancomycin-resistant Staphylococcus aureus (VRSA).

• Multi-drug resistant Mycobacterium tuberculosis (MDR-TB).

• Extensively resistant Mycobacterium tuberculosis (XDR-TB), etc.

With time, several multidrug-resistant pathogens have developed. The term "superbug" has been used commonly to refer to such microorganisms. If appropriate countersteps aren’t taken by the consumers and the concerned authorities, by the year 2050, AR infections could cause ~10 million deaths worldwide! This would lead to unprecedented economic losses as well.

Conclusion

• Antibiotics are drugs that exhibit bactericidal or bacteriostatic action against many pathogenic bacteria.

• Antibiotics may be produced either naturally or synthetically, and may be broad-spectrum or narrow-spectrum.

• Antibiotics are used not only for the treatment of pathogenic infections in humans but also as growth promoters in animal husbandry.

• Antibiotics have different modes of action including inhibition od cell wall synthesis, inhibition of cell membrane, inhibition of nucleic acid synthesis, etc.

• Continued injudicious use of antibiotics has led to the development of antibiotic-resistant strains of many pathogenic bacteria, such as the MRSA, VRSA, MDR-TB, etc.

• Mechanisms of antibiotic resistance include efflux pumps, inactivation of the drug, modification of the antibiotic or the target, etc.

FAQs

Q1. What is meant by combination therapy?

Ans. Combination therapy refers to the use of more than one drug or any other form of medication, to treat a particular disease, such as the treatment of a multi-drug resistant pathogen.

Q2. What is the difference between MDR-TB and XDR-TB?

Ans. MDR-TB is the strain of Mycobacterium that resists the first line of anti-tuberculosis drugs, namely, isoniazid and rifampicin. XDR-TB on the other hand resists not only these two drugs but also those that were formulated as the second line of defense, namely fluoroquinolone and injectable drug-like kanamycin, capreomycin, etc.

Q3. What are some side effects of using antibiotics?

Ans. Diarrhea, vomiting, allergies, and rashes are commonly reported side effects of antibiotics.

Q4. How is it that antibiotics don’t harm humans?

Ans. This is because the antibiotics selected for the treatment of humans are selectively toxic. Selective toxicity refers to the ability of antibiotics to harm the pathogen without inflicting damage to the host.

Q5. What are the alternatives to the increasing resistance to antibiotics?

Ans. The use of monoclonal or polyclonal antibodies has been suggested in recent years as an alternative to combat the increasing cases of antibiotic resistance.