Heidi Contreras

Bio: Heidi Contreras is an academic researcher from City of Hope National Medical Center. The author has contributed to research in topics: Modified vaccinia Ankara & Heme. The author has an hindex of 9, co-authored 17 publications receiving 750 citations. Previous affiliations of Heidi Contreras include Biodesign Institute & Beckman Research Institute.

Three Mycobacterium tuberculosis Rel Toxin-Antitoxin Modules Inhibit Mycobacterial Growth and Are Expressed in Infected Human Macrophages

Abstract: Mycobacterium tuberculosis protein pairs Rv1246c-Rv1247c, Rv2865-Rv2866, and Rv3357-Rv3358, here named RelBE, RelFG, and RelJK, respectively, were identified based on homology to the Escherichia coli RelBE toxin:antitoxin (TA) module. In this study, we have characterized each Rel protein pair and have established that they are functional TA modules. Overexpression of individual M. tuberculosis rel toxin genes relE, relG, and relK induced growth arrest in Mycobacterium smegmatis; a phenotype that was completely reversible by expression of their cognate antitoxin genes, relB, relF, and relJ, respectively. We also provide evidence that RelB and RelE interact directly, both in vitro and in vivo. Analysis of the genetic organization and regulation established that relBE, relFG, and relJK form bicistronic operons that are cotranscribed and autoregulated, in a manner unlike typical TA modules. RelB and RelF act as transcriptional activators, inducing expression of their respective promoters. However, RelBE, RelFG, and RelJK (together) repress expression to basal levels of activity, while RelJ represses promoter activity altogether. Finally, we have determined that all six rel genes are expressed in broth-grown M. tuberculosis, whereas relE, relF, and relK are expressed during infection of human macrophages. This is the first demonstration of M. tuberculosis expressing TA modules in broth culture and during infection of human macrophages.

Dysbiosis and the immune system

Abstract: Throughout the past century, we have seen the emergence of a large number of multifactorial diseases, including inflammatory, autoimmune, metabolic, neoplastic and neurodegenerative diseases, many of which have been recently associated with intestinal dysbiosis - that is, compositional and functional alterations of the gut microbiome. In linking the pathogenesis of common diseases to dysbiosis, the microbiome field is challenged to decipher the mechanisms involved in the de novo generation and the persistence of dysbiotic microbiome configurations, and to differentiate causal host-microbiome associations from secondary microbial changes that accompany disease course. In this Review, we categorize dysbiosis in conceptual terms and provide an overview of immunological associations; the causes and consequences of bacterial dysbiosis, and their involvement in the molecular aetiology of common diseases; and implications for the rational design of new therapeutic approaches. A molecular- level understanding of the origins of dysbiosis, its endogenous and environmental regulatory processes, and its downstream effects may enable us to develop microbiome-targeting therapies for a multitude of common immune-mediated diseases.

Interactions between the microbiota and pathogenic bacteria in the gut

Abstract: The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases.

Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease.

Abstract: The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co-evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.

Microorganisms with claimed probiotic properties: an overview of recent literature.

Abstract: Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Health benefits have mainly been demonstrated for specific probiotic strains of the following genera: Lactobacillus, Bifidobacterium, Saccharomyces, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, Bacillus, Escherichia coli. The human microbiota is getting a lot of attention today and research has already demonstrated that alteration of this microbiota may have far-reaching consequences. One of the possible routes for correcting dysbiosis is by consuming probiotics. The credibility of specific health claims of probiotics and their safety must be established through science-based clinical studies. This overview summarizes the most commonly used probiotic microorganisms and their demonstrated health claims. As probiotic properties have been shown to be strain specific, accurate identification of particular strains is also very important. On the other hand, it is also demonstrated that the use of various probiotics for immunocompromised patients or patients with a leaky gut has also yielded infections, sepsis, fungemia, bacteraemia. Although the vast majority of probiotics that are used today are generally regarded as safe and beneficial for healthy individuals, caution in selecting and monitoring of probiotics for patients is needed and complete consideration of risk-benefit ratio before prescribing is recommended.