Development of Antibiotic Resistance Flashcards
- Resistance to _______ - occurring antibiotics developed early in the _______ of microorganisms
- The rapid spread of resistance of some antibiotics is attributed to ______ ____ transfer and selective ______ due to the presence of the antibiotics in the _______
- Antibiotic resistance does not occur due to the ______ of the antibiotic. The antibiotic works as a selection mechanism to suppress _______ bacteria and favor growth of _______ ones
- naturally; evolution
- horizontal gene; pressure; environment;
- action; susceptible; resistant
Origins of Antibiotic Resistant Genes
- Resistance genes evolved ________ widespread use of _______
- Resistance genes may have ________ in microorganisms that produce ________
- Resistance genes may have ______ from common __________ genes
- Resistance can arise from _________ mutation, but at a very low _______
- before; antibiotics
- originated; antibiotics
- evolved; housekeeping
- spontaneous; frequency
Development of Antibiotic Resistance Example
- ___: Gene resistant to penicillin
- Mutation in ____ can also lead to penicillin resistance
- lamB
- PBP
Resistance Mechanisms
- ________ of the cell, the less _______ the cell the ______ number of antibiotics that will be effective against it. Acid-fast (_____ ___) > Gram Negative (_____ _____) > Gram Positive
- Mutation alters the ______ site of the antibiotic
- Acquisition of _____ whose products pumps _______ out of the cell, like a _____- pump
- Acquisition of a _____ whose product blocks ______ of the antibiotic to the _____ site. _________ _______: A protein binds to the _______ so it’s still active but antibiotics can no longer bind, seen with tetracycline
- Acquisition of a gene whose product _____ or _____ the antibiotic
- Permeability; permeable; fewer; mycolic acid; outer membrane
- target
- genes; antibiotic; tetracycline
- gene; binding; target; Ribosome Protection; ribosome
- Modifies; destroys
Multi-Drug Resistance (MDR) Pumps
- Located within the _______ _______ of bacteria
- Example of _______ transport where _______ are brought in
- ______ ____ ___(___) _____ _____: Remove aminoglycosides and fluoroquinolones
- ______ ___ ______(___): Removes chlorhexidine and antiseptics, found in Staphylococcus _______. Specific to Gram _________ bacteria
- _______ ______ _______ (___)_____: Removes antiseptics
- ____-_____-___ ___(__) ______: Can remove multiple drugs and has a protein component extending into the outer membrane. See in _________ coli, and _________ aeruginosa. Specific to Gram _______ bacteria
- ___-_____ _____(___) _____: Can remove multiple drugs by cleaving ATP, seen in _________ lactis. Specific to Gram ________ bacteria
- cytoplasmic membrane
- symport; cations
- Multi Antimicrobial Extrusion (MATE) Protein Family
- Major Facilitator Superfamily (MFS); aureus; Positive
- Small Multidrug Resistance (SMR) Family
- Resistance-nodulation-cell division (RND) Superfamily; Escherichia; Pseudomonas; Negative
- ATP-binding Cassette (ABC) Superfamily; Lactobacillus; Positive
Acquisition of a Gene Whose Product Modifies the Antibiotic
Chloramphenicol Resistance:
-_______ ________: Converts hydroxyl groups to O-acetyl groups inactivating them
Penicillin Resistance:
-__-________/_______(____ gene): Cleaves the β-lactam bond inactivating the antibiotic
- Chloramphenicol Transacetylase
- β-lactamase/Penicillinase (lamB gene)
Many Mechanisms of Tetracycline Resistance
-______ ________: Sensitive cells actively take up tetracycline into the cytoplasm via _____ and ____ pumps
Tetracycline Resistance:
1. _______ in the 30S ribosome subunit
2. Enzymatic ________ of the tetracycline via Destructases
3. Acquisition of a _____ whose product binds to the 30S subunit, results in ________ protection
4. Acquisition of a ____ whose product ____ tetracycline out of the cell, called _____
-All of the genes are located on ______
- Tetracycline Sensitivity; porins; proton
1. Mutations
2. Inactivation
3. gene; ribosome
4. gene; pumps; efflux - plasmid
Rise of β-Lactamases
- In 1990 the appearance of ___-_-Lactamases
- _____ _____ _-_____: Hydrolyze expanded spectrum cephalosporins such as Cefotoxamine
- Now there are over ____ occurring β-lactamases due to overuse
- CTX-M-Lactamases
- Extended Spectrum β-Lactamases
- 900
-___________ pneumoniae have become increasingly resistant to Carbapenem
-Klebsiella
Consequences of Carbapenem-resistant Enterobacteriaceae (CRE)
- Enteric Gram ________ bacteria that lead to intestinal infections and _______
- First reported in ________ Carolina in 2001
- By 2015, CRE have been found in infections in ____ states, and kill _____ of patients who get _________ infections
- ________ was considered to be the drug of last resort
- Feared that ______ will be the new superbug
- Negative; diarrhea
- North; 48; half; intestinal
- Carbapenem
- CRE
How Antibiotic Resistance Genes Spread
- Not typically due to ______ mutations
- Primarily due to the _____ of ________ plasmids and ______ transposons via _____ _______ ______
- ________ is a more limited method, penicillin resistance is via a ______ mobilized by __________ and _______ bacteriophages
- Spontaneous
- transfer; conjugative; conjugative; horizontal gene transfer
- Transduction; Staphylococcus; Salmonella
Consequences of the Uncontrolled Clinical Use of Antibiotics
- CDC believes that _____ million Americans are sickened and _______ killed annually due to unrestricted use of antibiotics
- Roughly ___ million Americans are infected and ________ killed annually by MRSA and other superbugs
- Carbapenem-resistant enterobacteriaceae (CRE) kill almost ______ of hospital patients who have ______ infections
- 2.25; 37,000
- 2; 23,000
- half; bloodstream
Consequences of the Uncontrolled Commercial & Clinical Use of Antibiotics
- _______ is the most commonly used antibiotic used in feed lots
- Feed antibiotics to farm animals to increase their ______
- Bacterial populations become exposed to ____ levels of antibiotics over a relatively _____ period of time
- Tetracycline
- weight
- low; long
Important Events in the Age of Antibiotics
- _____ _____ and ______ ______ Semmelweis advocated hand washing
- Between _____-_____ was the Golden Age for the discovery of antibiotics
- New method to create new antibiotics is through ________
- Rise of the Superbugs after _______, like _____ _____ _____ TB (___-TB) and MRSA
- Joseph Lister; Ignaz Philipp Semmelweis
- 1938-1950
- Modification
- 2000; Extended Drug Resistant
Potential Superdrugs
-________ is thought to be the last useful antibiotic to be used in fighting an infection
_________ 3.0 has been modified in 3 positions:
1. ___________ Group
2. _______ _______ Group, used in hand washing
3. _________ Substitution
-_______: Was discovered in 2015 at Novobiotic Pharmaceuticals in the Gram Negative soil bacteria Eleftheria terrae
- Vancomycin
- Vancomycin
1. Chlorobiphenyl
2. Quaternary Trimethylammonium
3. Methylene - Teixobactin