Microbiology and Antibiotics Overview

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Questions and Answers

What is the role of imipenem in treating infections?

Ineffective against Gram negative rods

Only used for viral infections

Used in treatment of mixed aerobic/anaerobic infections (correct)

Effective against Gram positive bacteria only

Which process significantly improved penicillin production during WWII?

Switching to surface culture methods

Using P.notatum exclusively

Eliminating corn steep liquor from production

Utilizing deep fermentation processes (correct)

Why is the β-lactam ring important for penicillins?

It has no effect on the activity of the antibiotic

It can easily be synthesized in large quantities

It must remain intact for the antibiotic to be effective (correct)

It is responsible for antibiotic resistance

What characterizes NDM-1 positive isolates?

Associated with resistance to multiple antibiotic classes Signup and view all the answers

Which of the following is a stable penicillin due to its structure?

Flucloxacillin Signup and view all the answers

What is one significant feature of the mecA gene?

It codes for an altered penicillin binding protein. Signup and view all the answers

Which antibiotic is noted as the only available oral treatment for MRSA infections?

Linezolid Signup and view all the answers

How does resistance to vancomycin occur in the Van A phenotype of Enterococci?

Through alteration in the ligase activity. Signup and view all the answers

What mechanism limits the effectiveness of vancomycin against bacteria that have developed resistance?

Switching from D-Ala-D-Ala to D-Ala-D-lactate. Signup and view all the answers

Which of the following is a consequence of the presence of PBP-2a in MRSA?

Alteration of antibiotic interactions. Signup and view all the answers

What type of infections is Daptomycin approved to treat as of 2006?

Complicated skin and skin structure infections caused by MRSA Signup and view all the answers

What is the primary role of the Vancomycin-resistant ligase in bacteria?

To synthesize an ester instead of an amide bond. Signup and view all the answers

What contributes to the resistance of MRSA to beta-lactam antibiotics?

Production of penicillin-binding proteins with altered structures. Signup and view all the answers

Which nucleotide does adenine (A) interact with for macrolide binding in bacteria?

A2058 Signup and view all the answers

What is the role of the erm gene in Streptococcus pneumoniae?

Methylates the ribosome to confer resistance Signup and view all the answers

What does the 'short course' treatment for tuberculosis include?

Isoniazid, ethambutol, pyrazinamide, and rifampicin Signup and view all the answers

What is the primary characteristic of mycobacteria compared to other bacterial organisms?

Thicker cell walls Signup and view all the answers

What is a major challenge in treatment for multi-drug resistant tuberculosis (MDR-TB)?

Use of 2nd line drugs that are more toxic and less effective Signup and view all the answers

How does the cell wall of mycobacteria contribute to its resistance?

By being hydrophobic and waxy Signup and view all the answers

During which process can the methylation of A2058 occur in Streptococcus pneumoniae?

Ribosome assembly Signup and view all the answers

What is the primary mechanism through which Directly Observed Therapy (DOT) improves tuberculosis treatment compliance?

Ensures patients take their medications as prescribed Signup and view all the answers

What is essential for the rapid bactericidal activity of daptomycin against Gram positive bacteria?

Calcium ions Signup and view all the answers

What mechanism allows daptomycin to induce cell death in bacteria?

Formation of large pores in the membrane Signup and view all the answers

Which genes are associated with resistance to daptomycin?

mprF and yycG Signup and view all the answers

Why are some strains of Staphylococcus aureus resistant to daptomycin?

Thickened cell walls preventing drug diffusion Signup and view all the answers

What was the original source of the daptomycin strain discovered by Eli Lilly and Co.?

Strain of Streptomyces roseosporus Signup and view all the answers

What is the primary structure type of daptomycin?

Lipopeptide Signup and view all the answers

Which synthetic antibacterial was discovered during the synthesis of chloroquine?

Nalidixic acid Signup and view all the answers

What effect do calcium ions have on daptomycin's interaction with the bacterial cell membrane?

Enhance daptomycin binding Signup and view all the answers

What is the primary action of co-trimoxazole in bacterial treatment?

It acts on two enzymes in the same biosynthetic sequence. Signup and view all the answers

What is the significance of lower doses of drugs in combination therapies like co-trimoxazole?

They reduce the risk of side effects and resistance. Signup and view all the answers

What is the role of transfer RNAs (tRNAs) during translation?

They bind to mRNA codons and carry amino acids. Signup and view all the answers

What are the components of the bacterial ribosome involved in protein synthesis?

30S and 50S subunits. Signup and view all the answers

During the process of translation, what happens to the tRNA after a peptide bond is formed?

It leaves the ribosome through the exit tunnel. Signup and view all the answers

What makes chloramphenicol a unique bacteriostatic agent?

It was initially derived from a bacterium but is synthetically prepared now. Signup and view all the answers

What is the function of the ribosome's P site during translation?

Holding the growing peptide chain. Signup and view all the answers

In protein synthesis, what occurs when the ribosome reaches a stop codon?

The peptide chain is released from the ribosome. Signup and view all the answers

Study Notes

Haemophilus influenzae

Associated with meningitis, bacteremia, pneumonia, and cellulitis.
Imipenem is effective against Gram-negative rods and mixed infections.

Penicillins

Developed by Chain, Florey, Abraham, and Heatley; Nobel Prize awarded in 1945 to Fleming, Chain, and Florey.
WWII saw advancements in penicillin production via deep fermentation, using large fermentation vessels.
Method modifications included using Penicillium chrysogenum and adding corn steep liquor, producing Penicillin G.
Limited range of penicillins due to the incorporation of mono-substituted acetic acids by molds.

β-Lactam Ring

Essential for penicillin function; must remain intact, as any destruction negates effect.
Sensitive to acidic conditions; semi-synthetic variations developed.

Key Penicillins

Flucloxacillin is acid-stable due to electron-withdrawing groups.
Amoxycillin is also acid-stable, containing a bulkier R1 group.

Carbapenemase

Rise in carbapenem-resistant genes (e.g., KPC, OXA, metallo-β-lactamase).
NDM-1 metallo-β-lactamase identified in 2008, spreads globally with multiple resistance traits.

Staphylococcus aureus

Causes skin infections, toxic shock syndrome, pneumonia, and meningitis.
Penicillin-resistant strains recognized since the 1960s; epidemic MRSA emerged in the 1990s.
Resistance mechanisms involve β-lactamase genes (blaZ) and chromosomal mecA, coding for altered PBPs (PBP-2a).
PBP-2a has a reduced affinity for β-lactams and contributes to multi-drug resistance.

Treatment for MRSA

Linezolid is the only oral antibiotic for MRSA infections.

Vancomycin

Targets D-Ala-D-Ala sequences to prevent wall cross-linking.
Vancomycin resistance arises from altered ligase activity, producing D-Ala-D-lactate, decreasing drug affinity.

Daptomycin (Lipopeptide)

Approved in 2003 for complicated skin infections caused by MRSA.
Also approved in 2006 for MRSA bacteraemia and endocarditis.
Binds to pulmonary surfactant, ineffective for pneumonia treatment.
Isolated from Streptomyces roseosporus; calcium ions enhance bactericidal activity.
Mechanism includes pore formation in membranes leading to cell death.

Resistance to Daptomycin

Point mutations in mprF and yycG genes related to phospholipid content and permeability.
Rare cases of daptomycin resistance commonly occur alongside vancomycin resistance.

Quinolone Antibacterials

Nalidixic acid discovered during chloroquine synthesis; represents synthetic antibacterials.
Co-trimoxazole exhibits sequential blocking on two enzymatic pathways to enhance efficacy.

Antibiotics Targeting Protein Synthesis

Multiple agents inhibit protein synthesis by targeting ribosomes.

Transcription and Translation

Transcription converts DNA to mRNA, which exits the nucleus.
Translation involves mRNA binding to ribosomes, facilitating amino acid assembly via tRNA.

Chloramphenicol

Originally derived from Streptomyces venezuelae; now synthetically produced.
Bacteriostatic with a broad spectrum, active form is R,R-isomer.

Resistance to Erythromycin

Resistance mechanisms include ribosomal modifications through erm genes.
Modifications involve dimethylation of A2058, reducing binding of erythromycin.

Tuberculosis (TB) Treatment

Primarily caused by Mycobacterium tuberculosis in pulmonary alveoli.
"Short course" consists of isoniazid, ethambutol, pyrazinamide, and rifampicin followed by rifampicin and isoniazid.
MDR-TB treatment is more toxic and lengthy, significantly increasing costs.

Mycobacteria

Aerobic and characterized by thick, hydrophobic cell walls containing mycolic acids.
Resistant to conventional cell wall synthesis inhibitors.

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Description

Explore important concepts related to Haemophilus influenzae, its infections, and the role of imipenem and penicillins in treatment. Learn about the historical contributions of scientists like Fleming, Chain, and Florey in the development of antibiotics and their production methods during WWII.