Abstract: This review focuses on the most recent advances in the application of probiotics as potential therapeutics for the developing world, from the treatment of chronic and acute enteric infections and their associated diarrheal complexes to the development of designer probiotics for controlling HIV and as novel mucosal vaccine delivery vehicles. ... Read more

Abstract: The use of Lactococcus lactis in novel biomedical applications is a fast evolving area of interest. Quite distinct from its traditional use in the dairy industries, L. lactis has emerged as a potential delivery vector for various antigens as well as therapeutic and immunomodulatory proteins. Many recent studies have shown promising results using in vitro or animal models. In addition, the oral administration of human interleukin 10 (hIL-10)-secreting L. lactis for the management and treatment of inflammatory bowel disease (IBD) has been the subject of recent clinical trials. These trials represent the first steps for the use of genetically modified L. lactis in clinical practice. In the present review we discuss some of the recent studies which investigate the use of L. lactis as an in vivo protein delivery system. The concept of biological containment in L. lactis using pyrimidine synthesis knock-out systems is also discussed. Finally we describe recent work evaluating living versus dead L. lactis vectors with particular emphasis on the use of Gram-positive Enhancer Matrix (GEM) particles as a novel delivery system. ... Read more

Abstract: The application of RNA interference-based gene silencing technologies has the potential to treat a variety of illness. Preclinical studies and some early clinical trials have already demonstrated the utility of small interfering RNAs (siRNAs) as a potential novel therapy for the treatment of cancer, viral infections, as well as a wide range of additional diseases. To be effective, an siRNA must be taken up by specific cells, enter the cytoplasm, and be loaded onto the Argonaute protein, the catalytic core of the RNA induced silencing complex (RISC) to direct the cleavage of the homologous transcripts. To meet this need, a variety of novel siRNA delivery strategies have been developed. As our understanding of the molecular mechanisms underlying the RNAi pathway has increased so has the ability to rationally design effective silencing and delivery strategies. This review will examine the latest advances in non-viral delivery of siRNA, with special reference to targeted siRNA delivery to specific target tissues and cell types in vivo in preclinical animal models. ... Read more

Abstract: One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response. ... Read more

Abstract: Chronic infection with the bacterial pathogen Helicobacter pylori is closely linked to the development of gastric cancer. Experimental infection of the laboratory mouse strain C57Bl6 mimics the initiation and progression of the disease in humans. Using this model, we have identified a dual role for CD4⁺ IFN-γ-secreting T-cells in the control of Helicobacter infection as well as in the induction of preneoplastic gastric pathology. High gastric expression of IFN-γ was positively correlated with a low Helicobacter burden, and was essential for vaccine-induced protection; on the other hand, elevated levels of the cytokine also, either directly or indirectly, triggered the transformation of the normal gastric mucosa to atrophic, hyperplastic and metaplastic lesions. Based on similar patterns of gene expression changes induced by IFN-γ in vivo and in cultured gastric epithelial cells, we hypothesize that IFN-γ may act directly on epithelial cells to stimulate their hyperproliferation, and thus to predispose them to elevated mutation rates and an increased risk of malignant transformation. ... Read more

Abstract: As research techniques and biotechnology advance, the risk for potential bioterrorism increases due to the ease of creating or modifying virulent pathogenic microorganisms. In addition, the destruction of natural habitats to a host of animals and microbial species that are normally sequestered in these areas may bring about new diseases to humans. ... Read more

Abstract: Mammals have not only allowed a large community of non-pathogenic bacteria to take up residence in their intestinal system, but they also rely on them for their own benefits and development. Intestinal commensal bacteria stimulated the polyclonal expansion of B lymphocytes that produce a diverse and effective antibody repertoire. ... Read more

Abstract: A lot has been learned since the 2001 mail anthrax attack. Authors analyzed the readiness of science and US government agencies in handling future bioterror attacks and proposed measures that would drastically improve the response efficiency and reduce the damage. ... Read more

“Between 500 and 1,000 microbial species colonize the mammalian colon to a density of approximately 10¹² bacteria per gram of content, comprising in total 100 times more cells than those that make up the host itself,” said Drs. Lanning and Knight in an article published in this issue of the journal. Given the immensity of the bacteria living inside our bodies, it is almost a miracle that they do not cause more trouble than they occasionally do (e.g., diarrhea, enterocolitis, imbalance of intestinal flora, etc.).

On the contrary, the commensal bacterial flora in the gut performs important, unconventional tasks ... Read more

Abstract: Infections acquired in the hospital during visits and hospitalization have happened to 2 million patients and cause 90,000 deaths in the U.S a year -- a staggering number beyond comprehension or common sense. Due to the mobility and persistence of drug-resistant bacterial infections, one hospital's infection control effort, balancing both cost and benefit to that hospital, may not make a significant impact in a large population base, but it would if all hospitals act together. ... Read more