Challenges of drug resistance

Role of antibiotics in microbes

Eliminating competition

Ecological signaling

What practices lead to antibiotic resistance

Overprescription of antibiotics

Incomplete courses of antibiotics

Overuse in agriculture

Inappropriate use

Environmental contamination

Main bacterial mechanism of resistance to antibiotics

Prevention of entry or expeling

Prevention of binding

Modification or dislodging of antibiotics

Reduced permeability

Mostly utilized by gram-negative, altering or downregulation of porins preventing antibiotic entry

Beta-lactamase

Enzyme that destroys beta-lactam antibiotics

Efflux pumps

Active transport system that pumps out antibiotics before they reach their target

Works on: beta-lactams, tetracyclines, and fluoroquinolones

Target site modification

Bacteria alter the structure of target molecules so antibiotic is unable to bind

What can cause resistance to methicillin and streptomycin

Modification of PBPs and ribosomal proteins

Modifying groups

Addition of group that inactivate the antibiotic

Examples of modifying groups

Acetyltransferases (AAC)

Phosphotransferases (APH)

Nucleotidyltransferases (ANT)

Ribosome protection

Resistance strategy utilized by gram positive bacteria where specialized protective proteins bind to ribosome and dislodge antibiotics; works on erythromycin antibiotics bound near peptidyl transferase site

Vertical gene transfer

Passing of genetic traits from parent to offspring during bacterial replication

Random mutations in the genome lead to resistance and is passed to next generation

Horizontal gene transfer

Exchange of genetic material between unrelated bacteria

Transformation

Transduction

Conjugation

Transformation

Uptake of free DNA from environment

DNA that encodes for resistant mechanisms

Transduction

Bacteriophages transfer DNA between bacteria

DNA that encodes for resistant mechanisms

Conjugation

Direct cell to cell transfer of plasmids

DNA that encodes for resistant mechanisms

Banning of antibiotic growth promoters

Reduction of unnecessary antibiotic use in agriculture

AGP

Antibiotics added to animal feed to promote faster growth

beta-lactamase inhibitors

block resistance enzymes

Efflux pump inhibitors

Stop bacteria from expelling antibiotics

Quorum sensing

Communication system utilized by bacteria to sense population density and coordinate group behavior

Interference with these to prevent bacterial coordination

Anti Persisters and anti-biofilms

Targeting of hard to kill bacteria states

Persisters

Dormant cells that survive antibiotics without being genetically resistant

Biofilm

Protective layers of bacteria that form on surfaces making them more drug resistant

Future directions of drug discovery research

Targeting microbiome

Bacteriophage therapy

Antivirulence strategies

Crispr and gene editing