Biofilm formation and antibiotic resistance on alginate beads of Staphylococcus aureus and other health care associated bacterial species
Why this work is in the frame
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Bibliographic record
Abstract
Health Care Associated Infections (HCAIs) are a concern especially in regards to antibiotic resistance and effective treatments. Staphylococcus aureus is often the main focus for eradication and prevention procedures, however, other bacterial species are also problematic. These include Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus epidermidis amongst others. Chronic infections caused by these bacteria are often biofilm related, and include dental caries, otitis media, osteomyelitis, burns & chronic wounds, and device related & prosthetic joint infections. Prosthetic joints and indwelling devices, such as catheters, are a prime environment on which biofilms can develop. This thesis aims to look at biofilms, investigating how they are established, the development of resistance against individual antibiotics and the antibiotic concentrations required to reduce biofilm load. A novel biofilm system – the alginate bead method will be used for these experiments, The alginate bead method was developed by a previous student in the Gallagher Laboratory, due to a need to have a reliable, robust and inexpensive technique to examine formation of biofilms and antibiotic resistance. There are devices and assays available, such as the Calgary Biofilm Device, which are extensively used for these purposes. However, the cost is prohibitive. This thesis found that the development of biofilms occurs much earlier than expected, with stable, fixed formation after just four hours of growth. Depending upon the antibiotic, resistance can develop within the first two hours of growth and thereafter steadily increases. By 24 hours the biofilms are fully resistant to all the tested antibiotics. In mixed species biofilms, the two species act synergistically protecting each other against the antibiotics, resulting in a much higher antibiotic concentration required. Common antibiotics used to treat staphylococcal infections are often combined to enhance their destructive effect and prevent the development of resistance. The effects of these antibiotics, when combined was explored. Biofilm resistance against gentamicin, one of the most common antibiotics used to treat staphylococcal infections develops quickly. However, when combined with other antibiotics gentamicin resistance is delayed. As antibiotic concentrations have to be extremely high in order to have any effect on established biofilms, alternative methods need to be investigated. Any alternative approaches would be employed in conjunction with conventional therapies preventing stable biofilm formation and disrupting established biofilms. Such methods may include sugar metabolites, enzymatic disruption, D-amino acids and activation of the quorum sensing system. The main conclusion which can be taken from this work are that firstly the alginate bead method of a viable, suitable alternative to the Calgary Biofilm Device and supports biofilm formation and testing. Secondly that biofilms form and are resistant to antibiotics much earlier than expected, and extreme concentrations of antibiotics are required to have an effect. Thus the inclusion of alternative methods which disrupt biofilms would be beneficial to clinical practice. However, the alternative methods investigated within this thesis (D-amino acids and sugar metabolites) failed to show any inhibition of biofilms. There are other possible choices which would need to be investigated.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it