Haemophilus Influenzae is a Small Gram Negative Bacillus - Medical Science Assignment Help

Assignment Task:

Task:

Background
Haemophilus influenzae is a small Gram-negative bacillus that is normal flora in the upper respiratory tract but also an important opportunistic pathogen that causes a range of infections including otitis media [Inflammation or infection located in the middle ear] and community-acquired pneumonia. These infections are frequently treated with antibiotics, but this approach is being hampered [v. ???????] by increasing levels of resistance.
In general, a B-lactam antibiotic enters the bacterial cell by passing through the outer membrane where it then binds to a molecule referred to as Penicillin-Binding-Protein 3 (PBP3) and this interrupts cell wall synthesis and inhibits growth. When an organism is resistant to a B-lactam antibiotic, this chain of events is compromised.
H. influenzae has multiple mechanisms of B-lactam resistance that involve different genetic events.The following series of questions are designed to test your understanding of the range of genetic events that can contribute to changes in genotype/phenotype (in this case the phenotype is antibiotic susceptibility/resistance).
Format
Answer with as much details as you can, with adequate reference to the information provided. Include diagrams where possible. Your answers must fit within 3 typed pages (12 point, palatino font with 1.5 line spacing – plus diagrams (diagrams are extra to the 3 pages). Referencing in the Vancouver style.A series of reference publications are provided for you as a starting point, these are NOT exhaustive.
https://pubmed.ncbi.nlm.nih.gov/17428889/ [free full text]https://pubmed.ncbi.nlm.nih.gov/22203122/ [provided as a PDF]https://pubmed.ncbi.nlm.nih.gov/17325223/ [free full text]
The Rubric for this assigment can be found HERE.
Criteria Description High distinction
Criteria 1 Part 1: 30% The genetic mechanisms behind dissemination of the TEM-1 bearing plasmids between strains of H. influenzae. was clearly and concisely explained.
The explanation for the transferences of gene for the B-lactamase between different plasmid types within H. influenzae and from E. coli to H. influenzae was clear and concise.

• All key concepts were discussed and linked throughout the section.
• The information was transformed into a format suitable for a non-discipline specific scientific audience
• Criteria 2 Part 2: 30% The student clearly and concisely explained how the change of amino acid confers ampicillin resistance and the nature of the genetic changes (at the nucleotide level) that have caused the amino acid substitution in the context of B-lactam resistance. All key concepts were discussed and linked throughout the section.
• The information was transformed into a format suitable for a non-discipline specific scientific audience  
• Criterion 3 Part 3: 30% The student clearly and concisely explained the genetic events that may have resulted in different amino acid substitutions in the context of PBP3. This was then expanded upon concisely to explain genetic events that resulted in distinctly different strains of H. influenzae in a certain location that are all resistant to ampicillin, all have the N526K substitution in PBP3 and the same “signature” “other” amino acid substitutions.
• All key concepts were discussed and linked throughout the section.
• The information was transformed into a format suitable for a non-discipline specific scientific audience 
• Criteria 4 Part 4: 10% referencing and structure Used a range of appropriate, current, and relevant references that provided evidence for concepts discussed.
• Referencing in the style of the Journal of Antimicrobial Chemotherapy
• Adhered to all structure guidelines.
• Writing style was clear and concise, adhering to scientific English conventions.
• The student has shown improvement based on feedback from StudiosityPart 1
• In some areas, up to 50% of strains of H. influenzae have a plasmid mediated B-lactamase (called TEM-1) and although in most situations the B-lactamase is on a large “plasmid” (more correctly called an integrative conjugative element “ICE”) it can also be found on a range of very small plasmids. In addition, this same B-lactamase is also widespread in E. coli, where it is located on a range of different plasmids (and these E. coli plasmids do not replicate in H. influenzae). It is known that the TEM-1 B-lactamase was present in strains of E. coli long before it was ever detected in H. influenzae.Please explain the genetic mechanisms behind the widespread dissemination of the TEM-1 bearing plasmids between strains of H. influenzae. Also explain how the gene for the B-lactamase may have been transferred between different plasmid types within H. influenzae and from E. coli to H. influenzae.
• Part 2
• Over the last decade, there has been a very dramatic increase in the prevalence of a different mechanism of B-lactam resistance. These strains have the normal amino acid asparagine (N) at position 526 in the PBP3 replaced with a lysine (K). These strains – referred to as BLNAR (B-lactamase negative ampicillin-resistant) seemed to occur simultaneously in different parts of the world.Please explain how the change of amino acid confers ampicillin resistance and explain the nature of the genetic changes (at the nucleotide level) that have caused the amino acid substitution. 
• Part 3 
• In addition to the N526K amino acid substitution referred to above, there is a range of other amino acid substitutions in PBP3 that may or may not also be present in some strains. These may increase resistance, but they also serve as “signatures” or “identifiers” of a particular PBP3.There have been some reports where distinctly different strains of H. influenzae in a certain location are all resistant to ampicillin, all have the N526K substitution in PBP3 and the same “signature” “other” amino acid substitutions. Please explain the genetic events that might have occurred here.
• Due date is the 12th of September at 8pm.

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