Understanding Of Host-microbe Interactions Research Articles

Cultivation of Epithelial-Associated Microbiota by The Immune System

Mounting evidence supports the intuitive idea that many of the factors produced in defense of the epithelial surface, including mucin and secretory IgA, promote the growth of the commensal microbial flora, much the same as plant-derived mucoid substances support the growth of symbiotic microbes in the rhizosphere associated with roots. Thus, the 'defense' of the host epithelial surface often involves support and maintenance of microbial growth, despite an unfortunate tendency to view the immune system as an antagonist to the microbial flora. The perspective that the immune system supports the growth of a symbiotic microbiota has the potential to push forward our understanding of host-microbe interactions and to facilitate the development of new treatments for diseases associated with the microbiota.

Metabolomics: Towards Understanding Host–Microbe Interactions

Metabolomics employs an array of analytical techniques, including high-resolution nuclear magnetic resonance spectroscopy and mass spectrometry, to simultaneously analyze hundreds to thousands of small-molecule metabolites in biological samples. In conjunction with chemoinformatics and bioinformatics tools, metabolomics enables comprehensive characterization of the metabolic phenotypes (metabotypes) of the human, and other mammalian, hosts that have co-evolved with a large number of diverse commensal microbes, especially in the intestinal tract. Correlation of the metabotypes with the microbial profiles derived from culture-independent molecular techniques is increasingly helping to decipher inherent and intimate host-microbe relationships. This integrated, systems biology approach is improving our understanding of the molecular mechanisms underlying multilevel host-microbe interactions, and promises to elucidate the etiologies of human disorders resulting from unfavorable human-microbial associations, including enteric infections.

The grand challenges to cellular and infection microbiology.

Almost one and a half centuries have passed since Robert Koch and Thomas Burrill made the seminal discovery that bacteria are responsible for mammalian and plant diseases. Shortly after, it was found that parasites, fungi, and viruses are also etiological agents of diseases in multi-cellular eukaryotes. As we roam the earth, we realize that we are outnumbered by the microbial community; that each of us has a microbiota which exceeds in numbers our own cells; and that the microbiota are essential components of our development and health. Another milestone was set by Robin Warren and Barry Marshall who discovered that a bacterium is responsible for gastric ulcer and gastric carcinoma, which earned them the 2005 Nobel Prize in Medicine, and changed our views and perspectives of other diseases. It opened the door to the possibility that microorganisms may be responsible for many other diseases of unknown etiology, such as Alzheimer's, gastrointestinal diseases of unknown etiology, and cardiovascular diseases. The past few decades have witnessed a quantum leap in our knowledge of microbe–host interactions. This has been fueled by the discovery of the polymerase chain reaction (PCR), the determination of a large number of genomic sequences, advancements in cell biology and immunology, and the development of various high throughput arrays for transcriptome and proteome analyses. As genomic sequencing has become more feasible, our understanding of pathogenic evolution and patho-adaptation to the host made tremendous strides. It is becoming clear that several of the specialized secretion systems are evolutionarily related to phages, and that phages may be an even more important driving force in the evolution of virulence than previously appreciated. In addition, novel approaches have been utilized to identify a myriad of microbial effectors that are delivered to targets in the host cell by elaborate type III–VII translocation devices leading to modulation of various cellular processes (Holland, 2010). The advances in genetic manipulations of eukaryotic cells, along with the development of various genetically defined animal models, have had and will continue to have tremendous impact on our knowledge of host–microbe interactions. Recent years have witnessed major progress in our understanding of innate immunity to infection, but we need to further expand our understanding of adaptive immunity, which has been lagging. Still, our progress in understanding host–microbe interactions has been nothing less than remarkable. Having said that, it is also quite fascinating how little this has helped in generating new vaccines for various infectious microbes or developing new therapies against multi-drug resistant bacteria. It is also astonishing how few viral infections have effective therapeutic agents or vaccines. This dichotomy clearly indicates that, although our excitement and hyperventilation about the new advances is well justified, we are only grasping the tip of the iceberg of host–microbe interactions, and our combined excitement and denial of this shallow understanding of host–microbe interactions keeps convincing us otherwise! There are numerous questions to be answered, as we dig deeper using the molecular reductionist approach, where the focus has switched from the big picture of the disease to the study of microbe–host interaction at the molecular level. Acknowledging these limitations, the “Grand Challenges” are put forth to encourage coordinated efforts to accomplish high impact goals that we currently think are unachievable. Setting targets for ourselves is essential for our ultimate aspiration of generating knowledge and platforms integrated across many biomedical disciplines that will benefit public health throughout the world. The challenges that Frontiers in Cellular and Infection Microbiology faces are highly interconnected, and overlap with those of many other biomedical disciplines.

Identification of host-induced pathogen genes by differential fluorescence induction reporter systems

The ability to monitor a pathogen's gene expression program in response to the host environment is central to understanding host-microbe interactions. This protocol describes the application of a fluorescence-based promoter trap strategy, termed differential fluorescence induction (DFI), to identify and characterize bacterial genes that are preferentially expressed in infected tissues. In this approach, animals are infected with a library of bacteria expressing random GFP transcriptional gene fusions, and fluorescent bacteria are recovered directly from host tissues using fluorescence-activated cell sorting (FACS). This methodology allows for the identification of bacterial promoters induced in distinct anatomical sites and at different stages of infection. Furthermore, unlike other methodologies, the use of the GFP reporter allows for single cell, temporal and spatial monitoring of pathogen gene expression in infected animals. Library construction, promoter identification and analysis can be done in 4-8 weeks.