A new approach for the discovery of antibiotics by targeting non-multiplying bacteria: a novel topical antibiotic for staphylococcal infections.

In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market.

The relationship between carotid stiffness and circulating levels of heat shock protein 60 in middle-aged men and women.

Objective: There is growing evidence that the presence of the cell stress protein heat shock protein (HSP) 60 in the circulation is associated with risk of coronary heart disease. In this study, we measured the association between plasma HSP60 and carotid arterial stiffness in middle-aged men and women.

Methods: Six hundred and forty-seven men and women aged 50-72 years and free of cardiovascular disease and medication were tested.

Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors.

The Whitehall Study is a prospective epidemiological study of cardiovascular risk factors in healthy members of the British Civil Service, which has identified psychological distress as a major risk factor for coronary heart disease. The levels of circulating Hsp60 in 860 participants from the Whitehall cohort and 761 individuals diagnosed with diabetes have been measured and related to psychological, biological, and genetic factors. In the Whitehall participants, concentrations of Hsp60 ranged from undetectable to mg/mL levels.

Differential regulation of circulating levels of molecular chaperones in patients undergoing treatment for periodontal disease.

Background: Evidence is emerging that molecular chaperones, in addition to their intracellular protein folding actions, can act as intercellular signaling proteins with an ability to modulate leukocyte function. Recent evidence has also shown that these proteins can exist in the circulation and may be involved in disease pathogenesis. We have used periodontitis and its treatment as a model of inflammation in the human to determine its effects on levels of circulating HSP10, HSP60 and BiP.

In situ immune response in brain and kidney during early relapsing fever borreliosis.

Characterization of the host immune response during initial pathogenesis of relapsing fever neuroborreliosis would be a key to understanding Borrelia persistence and factors driving the inflammatory process. We analyzed immune cells in brain and kidney with the highly invasive B. crocidurae during the first two weeks of murine infection.

Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease.

It is only some forty years since the discovery of the heat shock or cell stress response and just over twenty years since the heat shock/cell stress response was linked to protein misfolding. The plethora of intracellular proteins which promote correct protein folding in the cell, variously termed molecular chaperones, heat shock proteins, or cell stress proteins, have only been identified in the last fifteen years. During this period it has also been discovered that: (i) molecular chaperones are potent immunogens with immunomodulatory activity and (ii) they can be secreted by cells and exhibit intercellular signaling actions.

Association between plasma levels of heat shock protein 60 and cardiovascular disease in patients with diabetes mellitus.

Aims: Evidence is accumulating to support the hypothesis that the release of heat shock protein (Hsp)60 into the circulation is associated with the development of coronary heart disease (CHD). As diabetes is a risk factor for CHD, it was of interest to determine Hsp60 blood levels in a cross-sectional cohort of diabetic patients, some of whom had cardiovascular disease, and relate levels to relevant biochemical markers.

Methods And Results: A total of 855 patients with T1DM or T2DM, recruited as part of the UCL Diabetes and Cardiovascular disease Study (UDACS), were assayed for plasma levels of Hsp60.

Whole-body imaging of sequestration of Plasmodium falciparum in the rat.

The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal.

Interaction between protein subunits of the type IV secretion system of Bartonella henselae.

In this study we used the yeast two-hybrid system to identify interactions between protein subunits of the virB type IV secretion system of Bartonella henselae. We report interactions between inner membrane and periplasmic proteins, the pilus polypeptide, and the core complex and a novel interaction between VirB3 and VirB5.