Inhibiting the Growth of Pathogens via Antimicrobials

Chemotherapy

When we use any chemical (drug) to treat any disease or condition.

Chemotherapeutic agent

Any drug used to treat any condition or disease.

Antimicrobial agent

A type of chemotherapeutic agent that treats an infectious disease, either by inhibiting or by killing pathogens in the body.

Antibacterial agents

Bacterial diseases are treated with.

Antifungal agents

Fungal diseases are treated with.

Antiprotozoal agents

Protozoal diseases are treated with.

Antiviral agents

Viruses are treated with.

Antibiotics

Substances produced by a microbe that kills or inhibits the growth of other microbes.

Semisynthetic antibiotics

Researchers modified antibiotics to widen their effect on pathogens and reduce side effects.

Amoxicillin

Penicillin has been modified to.

Penicillin

The first antibiotic to be discovered.

Alexander Fleming

Who discovered penicillin.

S.aureus

The fungus Penicillium (a mold) secreted a substance that inhibited growth.

Ideal antimicrobial agent

Killed or inhibited the growth of some pathogens, was stable when stored in solid or liquid form, remained in tissues of the body long enough to be effective, when used correctly killed pathogens before they mutated and became resistant, caused no damage to the host.

Mechanisms of action of antimicrobial agents

1. Inhibition of cell wall synthesis 2. Damage to cell membranes 3. Inhibition of nucleic acid synthesis (either DNA or RNA) 4. Inhibition of protein synthesis 5. Inhibition of enzyme activity.

Bacteriostatic drugs

Inhibit growth of bacteria.

Bactericidal drugs

Kill bacteria.

Narrow-spectrum antibiotics

Some antibiotics only destroy one type of bacteria (e.g., Gram negatives).

Broad-spectrum antibiotics

Some antibiotics destroy a larger group of bacteria (e.g. Gram +/-).

Multidrug therapy

If multiple drugs are applied together.

Synergistic

They work together to produce a greater effect.

Antagonistic

The drugs work against each other.

Antifungals

Work on fungi.

Ergosterol

Antifungals mainly work by binding to cell membranes via ergosterol (found in fungal cell walls) and interfering with ergosterol synthesis.

Antiviral drugs

Generally work by inhibiting viral replication inside cells.

Drug cocktails

Several antiviral drugs that are administered simultaneously to treat HIV infection.

Development of superbugs

Occurs if not all pathogen cells are killed during treatment, leading to mutations that give them resistance.

Superbugs

Microbes (mainly bacteria) that have become resistant to one or more antimicrobial agents.

Examples of bacterial superbugs

Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), multidrug-resistant Mycobacterium tuberculosis (MDRTB), multidrug-resistant strains of Pseudomonas.

Intrinsic resistance

Lack specific target sites for a drug, or the drug cannot get across the cell wall or cell membrane.

Alter drug-binding sites

Bacteria may change the drug-binding site so that the drug can become ineffective.

Alter cell wall or cell membrane

Bacteria can modify these structures when the drug targets the outside of the cell specifically.

Inactivating the drug

Some bacteria develop new enzymes to destroy antibiotics.

Penicillinase enzyme

Destroys penicillin.

MDR transporter or efflux pumps

Pumps in bacterial membranes that can actively remove drugs from the cell.

Drug resistance mutations

Arises from mutations in chromosomes that give rise to new functions, maintained by natural selection.

Genetic info sharing

Those that survive can also share genetic information.

Transduction

Sharing genetic information via viruses.

Transformation

Uptake of naked DNA.

Conjugation

Sharing genetic information via sex pilus and pores.

β-Lactamases

A very important group of enzymes that inactivate penicillin and other similar antibiotics.

β-lactam ring

Every penicillin (and similar molecules) contain a double-ringed structure, with one ring being this.

β-lactamase inhibitor

Special drugs developed by combining a β-lactam antibiotic with this type of inhibitor.

Concerns of antimicrobial use

Include developing allergies, toxicity increase with dosage increase, destruction of normal microbial flora, and overgrowth of other microbes (superinfection).