Microbio: Module 11 - Control of Microbial Diseases

Bacterial cell walls are unique, contain peptidoglycan; great target for medications; often have high therapeutic index

What is the structure of the cell wall synthesis inhibitors?

Inhibit enzymes that catalyze formation of peptide bridges between strands of Peptidoglycan, disrupt cell wall synthesis, weaken cell wall → all lead to cell lysis

Mechanism: Cell Wall Synthesis Inhibitors

Only effective against actively growing cells, usually more effective in Gram+ bacteria

Limitations: Cell Wall Synthesis Inhibitors

Methicillin, Carbapenem, Vancomycin,

Examples: Cell Wall Synthesis Inhibitors

Very narrow (targeting specific gram-positive bacteria) to ultra-broad (targeting a wide array of gram positive, gram negative, and anaerobic bacteria)

Spectrum of Activity: Cell Wall Synthesis Inhibitors

Exploits differences between prokaryotic (70S) and eukaryotic (80S) ribosomes; block translation

Mechanism: Protein Synthesis Inhibitors

Gram + and gram -

Spectrum of Activity: Protein Synthesis Inhibitors

Some toxic due to mitochondria also have 70s ribosomes; aminoglycosides ineffective and macrolides limited activity against anaerobic bacteria

Limitations: Protein Synthesis Inhibitors

Tetracyclines and aminoglycosides

Examples: Protein Synthesis Inhibitors

Block DNA replication (gyrase) and block RNA polymerase (transcription)

Mechanism: Nucleic Acid Synthesis Inhibitors

Both major classes bactericidal and broad spectrum

Spectrum of Activity: Nucleic Acid Synthesis Inhibitors

Development of resistance

Limitations: Nucleic Acid Synthesis Inhibitors

Fluroquinolones and rifamycins

Examples: Nucleic Acid Synthesis Inhibitors

Antimetabolites competitively bind with enzymes (molecular mimicry) rendering them inactive

Mechanism: Metabolic Pathway Interference

Bacteriostatic and broad spectrum

Spectrum of Activity: Metabolic Pathway Interference

Biological compensation, metabolic toxicity, and network redundancy

Limitations: Metabolic Pathway Interference

Sulfa drugs and trimethoprim

Examples: Metabolic Pathway Interference

Damage between bacterial membranes → causes cells to leak, leading to death

Mechanism: Cell Membrane Interference

Narrow

Spectrum of Activity: Cell Membrane Interference

Topical applications only due to toxicity

Limitations: Cell Membrane Interference

Daptomycin and Polymyxin B

Examples: Cell Membrane Interference

Sterilization completely eliminates all forms of microbial life, including highly resistant bacterial spores whereas disinfection only reduces the number of harmful microorganisms to a safe level, but typically leaves some spores and resistant bacteria behind

Explain the difference between disinfection and sterilization.

Disinfection

Killing or inactivating microbes that cause disease

Sterilization

Destroying all live microbes, spores, and viruses

A disinfectant is only used on inanimate objects and surfaces since it is too toxic to the body whereas an antiseptic can be used on living body and tissues

Explain the difference between a disinfectant and antiseptic.

Disinfectant

Can be used on inanimate objects and surfaces but it is too toxic to the body

Antiseptic

Can be used on living body and tissues (ex: wound)

Physical: Heat (sterilization) by incineration, Heat (disinfect) by boiling, and chemical: hydrogen peroxide (disinfect)

Name at least three chemical and physical disinfection/sterilization methods and note whether they disinfect or sterilize objects.

Penicillin became the first antibiotic used in 1941 but didn’t become a prescription drug until mid-1950’s and sulfa drugs were the first “wonder” drugs and were considered antimicrobials, not antibiotics, because they are synthetic; sulfa drugs also saved millions of lives in WWII

Briefly summarize the history of penicillin and sulfa drugs.

Cause greater harm to microbes than their host, Interfere with essential structures or properties common in microbes but not in human cells, and Toxicity is relative and expressed as therapeutic index

What are the characteristics of antimicrobial medications: Selective Toxicity

Bacteriostatic vs. bactericidal

What are the characteristics of antimicrobial medications: Antimicrobial Action

Broad-spectrum vs. narrow spectrum

What are the characteristics of antimicrobial medications: Spectrum of Activity

Antagonistic, Synergistic, and Additive

What are the characteristics of antimicrobial medications: Effects of combinations

Antagonistic

Interfere with each other

Synergistic

One medication enhances another

Additive

Medications neither antagonistic or synergistic

Antimicrobials differ in behavior in body: Blood-brain barrier, pH, Half-life

What are the characteristics of antimicrobial medications: Tissue distribution, metabolism and excretion

Allergic reactions, toxic effects, dysbiosis of normal flora

What are the characteristics of antimicrobial medications: Adverse Effects

Certain bacteria have innate or intrinsic resistance and Bacteria may develop acquired resistance

What are the characteristics of antimicrobial medications: Resistance to antimicrobials

A physician may choose a broad-spectrum antibiotic for its speed, severity, and complexity over a narrow spectrum but a major drawback is that it kills both harmful and helpful bacteria

Explain why a physician may choose a broad-spectrum antibiotic over a narrow spectrum of antibiotics. What is one of the drawbacks of using a broad-spectrum antibiotic?

Because bacteria reproduce rapidly and adapt to survive and resistance spreads faster today due to drug overuse, patients stopping treatments early, agriculture and global travel

Explain why antibiotic resistance is inevitable in bacterial species, but why we are seeing it happening at an increasing rate.

Antibiotics saved millions of lives in WWII and successfully cured bacterial infections that were once deadly but antibiotic resistance is making common infections harder to treat, increases hospitalizations, and makes procedures like surgeries and chemotherapy far riskier

Briefly summarize the impact that antibiotics have on healthcare and the detrimental effects of the rise in antibiotic resistance.

Enzymatic inactivation, Alter antibiotic uptake (membrane pump and decrease membrane permeability), Modify target of antibiotic, and Develop alternate metabolic pathway

Summarize the five mechanisms of antibiotic resistance.

Through transduction where resistance genes can be transferred from one germ to another via phages; Conjugation where resistance genes can be transferred between germs when they connect; and Transformation where resistance genes released from nearby live or dead germs can be picked up directly by another germ

How can bacterial cells acquire new antibiotic resistance capabilities?

Transduction

Resistance genes can be transferred from one germ to another via phages

Conjugation

Resistance genes can be transferred between germs when they connect

Transformation

Resistance genes released from nearby live or dead germs can be picked up directly by another germ

Transduction, conjugation, and transformation

How can bacterial cells acquire new antibiotic resistance capabilities? List the 3 ways

When people misuse antibiotics (like taking them for viral colds or stopping treatment too early), the drugs kill off weak bacteria but leave behind stronger, mutant ones. These survivors multiply without competition and spread their dangerous defense traits to other bacteria, creating “superbug” infections

Explain the process that happens when people misuse antibiotics and how it leads to the spread of resistant bacteria.

Overuse of antibiotics, inappropriate prescribing, and extensive agricultural use

What are the 3 main factors that are driving the rise of antibiotic resistance?

Drives evolution of resistance through purchasing online and lack of regulation

Explain the overuse of antibiotics

Treatment indication, choice of agent, or duration of antibiotic therapy is incorrect in 30-50% of cases; antibiotics aren’t effective against viruses

Explain inappropriate purchasing

80% of antibiotics sold in the US are used in animals to promote growth and prevent infections and 90% of antibiotics given to livestock are exceted then widely dispersed through fertilizer, ground water, and surface runoff

Explain extensive agricultural use

When hardy, drug-resistant bacteria or their genetic codes leave these specialized environments; in agriculture, this can be through animal manure, contaminated crops and soil, food supply or direct contact; in hospitals, this can be through high antibiotic use, poor hand hygiene, contaminated equipment, patient discharge

Summarize how antibiotic resistance can spread to the community setting through agriculture and the healthcare setting.

By stopping germ spread and ensuring drugs are used correctly and this can be done through strict hand hygiene, supporting antibiotic stewardship to avoid unnecessary prescriptions, following infection control protocols, promoting vaccinations, and safely transferring patient data between facilities

What strategies can healthcare workers employ to prevent the spread of antibiotic resistance?

Because bacteria naturally and inevitably evolve to resist new drugs faster than we can discover them

Why can’t we rely on the production of new antibiotics to solve the problem of antibiotic resistance?

Stop germs from getting stronger as they prevent you from getting sick in the first place; they protect the population so germ’s can’t be spread, and they fight an active infection to kill the good and bad germs inside you

Describe the following alternatives to antibiotics that are being developed: Vaccines

Are lab made proteins designed to mimic your body’s natural defenses by attaching only to the harmful bacteria and leaving the good bacteria alone

Describe the following alternatives to antibiotics that are being developed: Antibodies

Natural viruses that specifically hunt and destroy bacteria

Describe the following alternatives to antibiotics that are being developed: Bacteriophages

Transfers healthy stool bacteria from a donor into a patient’s gut; instead of killing all bacteria with drugs, this restores the natural bacteria in your gut

Describe the following alternatives to antibiotics that are being developed: FMT (Fecal Microbiota Transplant)

There have been cases in which individuals dying of multidrug resistant infections made complete recoveries through phage therapy, in one instance involving genetically engineered phages

Describe the following alternatives to antibiotics that are being developed: Other alternative agents

Prevent viral entry, interfere with viral uncoating, interfere with viral nucleic acid synthesis, prevent genome integration and prevent assembly and release of viral particles

What are the targets of antiviral agents?

Prevent Viral Entry (Mechanism of Action)

Interferes with binding of HIV to host cell receptors

Interfere with viral uncoating (Mechanism of Action)

Nucleic acid must separate from protein coat in order for replication to occur

Interfere with viral nucleic acid synthesis (Mechanism of Action)

Non nucleoside polymerase inhibitors inhibit viral polymerases by binding to site other than nucleotide-binding site and non nucleoside reverse transcriptase inhibitors inhibit RT by binding to site other than nucleotide-binding site that is often used with nucleoside analogs to treat HIV infections

Prevent genome integration (Mechanism of action)

Inhibits integrase in HIV and is a new option for treating HIV infections

Prevent assembly and release of viral particles (Mechanism of action)

Inhibits enzymes needed for assembly and release