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.