In contrast to the host response, the transcriptional response of S. aureus varied significantly between control and diabetic mice. We observed a significant increase in gene induction associated with translation while decreases in amino acid transport as well as genes of unknown function. This does contrast slightly to a study that examined S. aureus expression in diabetic rats in an endocarditis model, whereby amino acid transport genes were upregulated (66), this just may be reflected of the significantly different infection models. Many of the upregulated genes of S. aureus under diabetic conditions were associated with heat shock and cellular stress, an interesting observation given our host expression data, suggestive the infection site …show more content…
The Clp proteases contribute to S. aureus subcutaneous skin infection. A) Hemolytic activity of spent culture supernatants from WT S. aureus and clp mutants. N=12-PBS, 13-WT, 12-clpC, 10-clpP and 6-clpX. WT C57Bl/6J mice were infected subcutaneously with WT S. aureus and clp mutants for 5 days. B) Areas of dermonecrosis over time. Black-WT, blue-clpC, red-clpP and green-clpX. C) Areas of dermonecrosis quantified at day 5. D) Bacterial counts from punch biopsies at day 5. Each point represents a mouse. Lines display median. ****P<0.0001, ***P<0.001, **P<0.01 and *P<0.05 relative to WT control.
Supplementary Figure legends
Supplemental Figure 1. Cytokine production in response to S. aureus skin infection. Multiplex cytokine analysis was performed on clarified material from homogenized skin biopsies. Mice, control and hyperglycemic (STZ-treated) were infected with 2 x 106 cfu of S. aureus for 1 or 6 days. N=3 for PBS uninfected mice, 8 for 1 day infected mice and 12 per group in the 6 day infected. *P<0.05 relative to WT infected.
Supplemental Figure 2. Additional cytokine production in response to S. aureus skin infection. Multiplex cytokine analysis was performed on clarified material from homogenized skin biopsies. Mice, control and hyperglycemic (STZ-treated) were infected with 4 x 106 cfu of S. aureus for 1 or 6 days. N=3 for PBS uninfected mice, 8 for 1 day infected mice and 12 per group in the 6 day infected. *P<0.05 relative to WT
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Effect of glucose exposure on macrophage reactive oxygen species production. Macrophages were grown in normal and high glucose for 2 days before exposure to S. aureus and levels of A) cellular ROS and B) mitochondrial ROS were measured. Each dot represents a biological replicate. Influence of hydrogen peroxide on C) cellular ROS production (N=2) and D) intracellular bacterial killing. N=4. E) Intracellular bacterial killing with superoxide dismutase (sodA) and catalase (katE) mutants of S. aureus. N=3. ****P<0.0001, ***P<0.001 and *P<0.05.
Supplemental Figure 5. Effect of glucose on macrophages glycolytic function. A) Glycolytic stress test performed on a Seahorse analyzer with macrophages treated under normal of hyperglycemic conditions. N=18. Macrophages were incubated with WT or a pyk deficient strain of S. aureus and assessed for B) intracellular survival (N=15) and C) ability to be taken up by the cells (N=3).
Supplemental Figure 6. Influence of glucose on human keratinocyte cell function. The human keratinocyte cells, HaCats or primary keratinocytes were grown under normal (6 mM) or high (50 mM) glucose conditions for 2 days. A) Intracellular survival of S. aureus in a gentamicin protection assay. N=10. B) Survival of S. aureus in extracellular milieu. N=14. C). Gentamicin protection again with primary keratinocytes. N=15. D) Uptake of AF647 labelled S. aureus. N=2 for PBS and 7 for S. aureus. E) Viability of keratinocytes after gentamicin protection
The immunologic events that are happening at the local level during Carlton's acute inflammatory response would be:
The guidelines’ first focus is the definition of sepsis, which makes sense, because there is no way to effectively treat sepsis without an accurate and categorical definition of the term. The guidelines define sepsis as “the presence (probable or documented) of infection together with systemic manifestations of infection”. Such systemic manifestations can include fever, tachypnea, AMS, WBC >12k, among others; these manifestations are listed in full in Table 1 of the guidelines. The definition for severe sepsis builds on to the definition of sepsis, bringing organ dysfunction and tissue hypoperfusion (oliguria, hypotension, elevated lactate) into the picture; full diagnostic criteria is listed in Table 2. The guidelines recommend that all
The immune system is made up of a network of cells, tissues, and organs that work together to protect the body, and it defends the body from “foreign invaders.” Immunity can be divided in two three different defenses, and these are defined as first, second and third lines of defense. The first line of defense for the immune system is the primary defense against pathogens entering the body from the surface in order to prevent the start of disease and infection. Some examples of the first line of defense is the skin, protecting the external boundaries of the body, and the mucous membranes, protecting the internal boundaries of the body. Although the skin and mucous membranes work on the internal and external boundaries, they both release chemicals
In addition to its traditional clinical manifestations, GAS can also cause serious invasive disease such as necrotizing fasciitis, colloquially known as the flesh-eating disease. First broadly reported during the Civil War, when it was known as gangrene, necrotizing fasciitis occurs when an individual’s subcutaneous fat and superficial fascia become rapidly necrotic. Though incidence data is limited, one study estimated that, worldwide, there are approximately 660,000 cases of invasive GAS disease per year, with 97% of those cases occurring in low-income populations (4). Many microorganisms other than GAS have been linked with necrotizing fasciitis, including Staphyloccocus aureus, Escherichica coli, and Klebsiella pneumoniae, and the disease is often caused by a polymicrobial infection. However, the most well known causative agent in necrotizing fasciitis cases is usually Group A streptococci (6). Although risk factors for necrotizing fasciitis include diabetes, old age, and immunosuppression, nearly half of all infections occur i...
Capriotti & Frizzell (2016) explain that sepsis is often seen in those who have a weak immune system. These individuals are at an increased risk of developing sepsis from microorganisms that a healthy immune system would normally fight off (Capriotti et al. 2016). The elderly, infants, and immunosuppressed patients are the most at risk for developing the condition (Capriotti et al. 2016). Sepsis can be caused by any microbe, but is most often caused by bacteria (Capriotti et al. 2016). Since sepsis has such a broad reach and can develop as a secondary infection after an initial injury or illness, Capriotti & Frizzell (2016) further explain the di...
Even though S. aureus is mainly associated with food poisoning, the bacterium can penetrate the skin or other mucous membranes to invade a range of tissues which will cause a variety of infections. Superficial infection of the skin can cause boils, impetigo, styes (infection of the glands or hair follicles of the eyelids), folliculitis, and furnacles. All of these infections are charac...
Necrotizing Fasciitis (flesh eating bacteria ) from an essay by Katrina Tram Duong, edited by S.N. Carson M.D.
Molin, M., Yang, J., Hanzen, S., Toledano, M., Labarre, J. and Nystrom, T. (2011). Life span extension and H2O2 resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. Mol Cell, 43 (5): 823-833. doi:10.1016/j.molcel.2011.07.027.
amount of glucose in the blood. This is because the body’s immune system is activated to
...in sources of energy. When cells cannot absorb sugar, you can become fatigued or feel exhausted” (Healhline), complain of blurred vision” In the short term, high glucose levels can cause a swelling of the lens in the eye. This leads to blurry vision. Getting your blood sugar under control can help correct vision problems. If blood sugar levels remain high for a long time, other eye problems can occur” (HealthLine), experience nocturia “Elevated glucose levels force fluids from your cells. This increases the amount of fluid delivered to the kidneys. This makes you need to urinate more. It may also eventually make you dehydrated” (Healthline), and have sores and cuts that will not heal “Elevated glucose levels may make it harder for your body to heal. Therefore, injuries like cuts and sores stay open longer. This makes them more susceptible to infection” (HealthLine).
Diabetic Ketoacidosis (DKA) is a serious disease with complications that may have fatal results in some cases. DKA is defined as an insulin deficiency that occurs when glucose fails to enter insulin into muscles such as: liver and adipose tissue. When there is an accumulation of ketones, it leads to metabolic acidosis which causes nausea and vomiting, as a result fluid and electrolytes are lost (Gibbs). There are many complications of diabetic ketoacidosis, some of the most prevalent are: Cerebral Edema, Hypoglycemia, and Acute Pancreatitis.
Barkley and Sherman (2013) indicated that protein energy malnutrition can prevent or prolong wound healing. However, studies have shown that up to 93% of malnourished people are living in the community and this continues to be a major clinical and public wound healing problem in the UK (Elia and Russell, 2009). Poor nutrition impacts on both the obese as well as the underweight patients. Over 34% of patients in the UK were found to be at risk of malnourishment in 2010 higher than the prevalence in 2008 (BAPEN) (2010). This is an indication that the population of people who are at potential risk of poor wound healing continue to increase. Nutritional factors thought to contribute to skin breakdown due to protein deficiency. The skin breakdown creates a negative nitrogen balance; anaemia, inhibits the formation of red blood cells; and dehydration, which causes dry, fragile skin. Nutrition plays a role in the prevention and treatment of wounds (Thompson and Furhrman, 2005). Horns et al, 2004 emphasize on fluids adequacy to maintain good skin tone and blood flow to tissues to prevent its breakdown (Horns et al, 2004). However, immune function declines with age, increasing the risk of infections and decreasing skin response to temperature,
Investigate the Effect of pH on Immobilised Yeast Cells on the Breakdown of Hydrogen Peroxide
Oxygen (O) is one of the most important ions present in the body, making up 61% of the body’s mass. It aids in the destruction of harmful bacteria, while preserving the bacteria that is beneficial for the body. Oxygen takes on its role, and transfers the bacteria absorbed into the lungs, to the cells, allowing for cell respiration. Oxygen allows for the replacement of old cells, protection of the new ones, production of energy from the food, and decomposition of other foods (“Oxygen and Human Body,” n.d.). Oxygen is also vital to produce an activity known as metabolism, which is ‘the sum of the physical and chemical processes in an organism by which its material substance is ...
The medical literature on treating wounds with honey has been reviewed recently in specialist wound-care journals, with a focus on the medical evidence (Molan, 1998) and with a focus on the clinical aspects (Molan, 1998). In the numerous reports in the medical literature on the use of honey as a wound dressing the types of wounds on which honey has been successfully used are very varied. Of particular note are the successful uses of honey to treat Fournier's gangrene (Subrahmanyam,1993) a rapidly spreading infection that is usually managed by aggressive surgical removal of infected tissue which are difficult to treat because they are in a position where it is difficult to prevent infection occurring. Also application of honey to wounds especially to chronic wound has been seen to heal faster unlike when some antibiotics are used. (Watts, R; Frehner, E, 2017). However, the therapeutic effects of the honey that have been observed has proven effective on different types