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Diabetic foot: microbiology, pathogenesis and glycan studies

Dharod, Meghna (2010) Diabetic foot: microbiology, pathogenesis and glycan studies. PhD thesis, University of Westminster, School of Life Sciences.

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Abstract

Complications of type 2 diabetes mellitus are one of the major causes of morbidity and mortality around the world. Diabetic foot infections remain one of the major complications leading to a leg loss every 3 seconds due to amputations causing mental trauma and distress. In diabetic foot ulcers aerobes, anaerobes and fungus often interact with each other and form biofilms which is difficult to treat, enhancing antimicrobial resistance and lead to a non-healing ulcer. Co-existing peripheral vascular disease and neuropathy exacerbate the problems. In T2DM patients’ minor cuts and wounds, often lead to hard to treat and chronic ulcers which can worsen to gangrene formation which may lead to osteomyelitis compromising the mechanics of the foot. It is necessary to identify the virulence factors of these clinically significant microbes and to identify the resistance patterns regularly to limit the antibiotic usage and target to the specific organisms. A Cohort studies were carried out in India and in the UK to identify the risk factors among the diabetic foot patients along with their microbial aetiology and antibiotic resistance patterns from the tissue and pus samples. This part of the research has shown the presence of mixed cultures mainly from the Indian diabetic foot ulcer specimens with higher percentages of anaerobes than aerobes. Multi-drug resistant organisms were one of the peculiar characteristics of the diabetic foot ulcer profiles of Indian patients. As compared to the Indian patients, UK patients had few resistant organisms and the patients admitted to hospitals in India were at the last stage of foot ulcers whereas in the UK, surveillance and preventative strategies allow early detection and intervention. Currently there is a lack of rapid, robust and an inexpensive diagnostic method for the rapid typing and identification of clinically significant anaerobes. Another part of the research focussed on utilising the glycan-lectin interactions by developing a simple enzyme linked lectin sorbent assay by employing biotinylated lectins to develop to an enzyme linked lectin sorbent assay (ELLA) on whole cells, Proteinase K treated cells and glycolipids of clinically significant aerobes and anaerobes. This study is concluded by utilising the glycan-lectin interactions and to develop a rapid typing method for clinically significant Methicillin resistant and sensitive Staphylococcus aureus and epidermidis species. The rapid identification of anaerobes and typing of Peptostreptococcus species was also by facilitated by the developed ELLA method. Finegoldia magna is one of the most significant anaerobes from soft tissue infections and the Gas Chromatography – mass spectrometry (GC-MS) of the glycolipids of Finegoldia magna on composition analysis using show the presence of sialic acid which could be involved in pathogenesis. This sugar may be one of virulence factor employed by this organism in either attachment to the host or to other organisms.

Item Type:Thesis (PhD)
Research Community:University of Westminster > Life Sciences, School of
ID Code:9552
Deposited On:07 Jul 2011 17:04
Last Modified:07 Jul 2011 17:04

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