Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.

The annexins, a family of Ca 2؉ -and lipid-binding proteins, are involved in a range of intracellular processes. Recent findings have implicated annexin A1 in the resealing of plasmalemmal injuries. Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin O. An injury-induced elevation in the intra- 2؉ -sensitivities provide a cell with the means to react promptly to a limited injury in its early stages and, at the same time, to withstand a sustained injury accompanied by the continuous formation of plasmalemmal lesions.The annexins are a family of Ca 2ϩ -binding proteins expressed in most phyla and species (1-4). Twelve annexins are present in vertebrates (A1-A11 and A13) with different splice variants (1). Annexins share a common folding motif, the "annexin core," which harbors the Ca 2ϩ -and membrane-binding sites (2-4). In their Ca 2ϩ -bound form, the annexins translocate from the cytoplasm to the plasma membrane and associate with negatively charged phospholipids (2-4). The N-terminal region precedes the conserved core and is unique for a given member of the annexin family. It mediates interactions with protein ligands and regulates the annexin-membrane association (2-4). Different annexins have been shown to orchestrate a variety of intracellular processes, ranging from the regulation of membrane dynamics to cell migration, proliferation, and apoptosis (2-12). However, the intriguing question why the majority of cells express several annexins, which differ only slightly in their biochemical properties, remains unanswered.Recent findings have implicated annexin A1 in the resealing of plasmalemmal lesions following cell injury (13,14). An injury-induced rise in the local concentration of intracellular Ca 2ϩ (15) is sensed by annexin A1 and triggers its binding to the plasma membrane at the site of the injury (13,14). Subsequently, annexin A1 promotes fusion of the damaged membrane around the pore, forming sealed, lesion-containing structures: large, cytosol-containing blebs (14) or smaller, cytosol-free microvesicles (16). The microvesicles subsequently can be shed by the cell (16, 17).Here, we show that, similar to annexin A1, annexin A6 is directly involved in the repair of plasmalemmal lesions induced by streptolysin O (SLO).2 The shedding of microvesicles appears to be predominant in the elimination of pores by annexin A6-dependent repair. Annexin A6 requires lower [Ca 2ϩ ] i for its plasmalemmal binding and, thus, responds faster to an injury than annexin A1. Correspondingly, a plasmalemmal lesion can be repaired by annexin A6 even without involvement of annexin A1; however, the concerted action of both annexins is instrumental for the efficient repair of multiple, simultaneously occurring plasmalemmal lesions. EXPERIMENTAL PROCEDURESReagents-Monoclonal anti-annexin A6 and anti-annexin A1 antibodies were from BD Biosciences; an antiserum against SLO was from Bioacad...

BackgroundSmuggling of illegal drugs by hiding them inside one’s own body, also called body packing, is a worldwide phenomenon. Cocaine is the most frequently transported drug. Body packing is a potentially lethal practice. The most serious complications of body packing are gastrointestinal obstruction or perforation and drug toxicity due to packet leakage or rupture.Case presentationA 30-year-old confirmed body packer was brought to our emergency department from jail because of agitation and mydriasis. He presented with a high respiratory rate of 40/min but normal oxygen saturation on ambient air, a heart rate of 116 bpm, a blood pressure of 116/68 mmHg and a temperature of 38.0° Celsius. Blood tests were suggestive of infection, urine analysis was positive for cocaine. Abdominal and thoracic computed tomography scans showed pulmonary infiltrates as a possible focus of infection; signs of bowel obstruction or perforation were absent. Given his clinical presentation, we suspected severe infection rather than massive cocaine intoxication to be the main problem. We therefore withheld immediate surgical decontamination. Instead, we started broad-spectrum antibiotic treatment with piperacillin/tazobactam plus clarithromycin for suspected severe community-acquired pneumonia or abdominal sepsis and treated the patient with intravenous midazolam for symptomatic cocaine intoxication. After detection of urinary pneumococcal antigen, the antibacterial regimen was changed to ceftriaxone and vancomycin for pneumococcal pneumonia. In addition, we found human immunodeficiency virus (HIV) type 1 infection as underlying disease. The patient recovered from his acute illness and was discharged after 7 days of treatment with ceftriaxone plus vancomycin. Antiretroviral therapy was started in an outpatient setting.ConclusionsWith this case report, we emphasize the need to look for alternative diagnoses to intoxication and gastrointestinal obstruction in acutely ill body packers with atypical presentation. Special risks, such as underlying HIV infection and potential antimicrobial resistance according to the individual’s geographical origin, should be taken into account while treating these patients.