Molecular Koch's postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen. Genes that satisfy molecular Koch's postulates are often referred to as virulence factors. The postulates were formulated by the microbiologist Stanley Falkow in 1988 and are based on Koch's postulates. [1]
As per Falkow's original descriptions, the three postulates are: [1]
To apply the molecular Koch's postulates to human diseases, researchers must identify which microbial genes are potentially responsible for symptoms of pathogenicity, often by sequencing the full genome to compare which nucleotides are homologous to the protein-coding genes of other species. Alternatively, scientists can identify which mRNA transcripts are at elevated levels in the diseased organs of infected hosts. Additionally, the tester must identify and verify methods for inactivating and reactivating the gene being studied. [2]
In 1996, Fredricks and Relman proposed seven molecular guidelines for establishing microbial disease causation: [3]
A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells.
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection.
Pathology is the study of disease and injury. The word pathology also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a narrower fashion to refer to processes and tests that fall within the contemporary medical field of "general pathology", an area that includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue and human cell samples. Idiomatically, "a pathology" may also refer to the predicted or actual progression of particular diseases, and the affix pathy is sometimes used to indicate a state of disease in cases of both physical ailment and psychological conditions. A physician practicing pathology is called a pathologist.
Koch's postulates are four criteria designed to establish a causal relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884, based on earlier concepts described by Jakob Henle, and the statements were refined and published by Koch in 1890. Koch applied the postulates to describe the etiology of cholera and tuberculosis, both of which are now ascribed to bacteria. The postulates have been controversially generalized to other diseases. More modern concepts in microbial pathogenesis cannot be examined using Koch's postulates, including viruses and asymptomatic carriers. They have largely been supplanted by other criteria such as the Bradford Hill criteria for infectious disease causality in modern public health and the Molecular Koch's postulates for microbial pathogenesis.
The germ theory of disease is the currently accepted scientific theory for many diseases. It states that microorganisms known as pathogens or "germs" can cause disease. These small organisms, too small to be seen without magnification, invade humans, other animals, and other living hosts. Their growth and reproduction within their hosts can cause disease. "Germ" refers to not just a bacterium but to any type of microorganism, such as protists or fungi, or even non-living pathogens that can cause disease, such as viruses, prions, or viroids. Diseases caused by pathogens are called infectious diseases. Even when a pathogen is the principal cause of a disease, environmental and hereditary factors often influence the severity of the disease, and whether a potential host individual becomes infected when exposed to the pathogen. Pathogens are disease-carrying agents that can pass from one individual to another, both in humans and animals. Infectious diseases are caused by biological agents such as pathogenic microorganisms as well as parasites.
The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.
Botrytis cinerea is a necrotrophic fungus that affects many plant species, although its most notable hosts may be wine grapes. In viticulture, it is commonly known as "botrytis bunch rot"; in horticulture, it is usually called "grey mould" or "gray mold".
Pathophysiology is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the medical discipline that describes conditions typically observed during a disease state, whereas physiology is the biological discipline that describes processes or mechanisms operating within an organism. Pathology describes the abnormal or undesired condition, whereas pathophysiology seeks to explain the functional changes that are occurring within an individual due to a disease or pathologic state.
Stanley "Stan" Falkow was an American microbiologist and a professor of microbiology at Georgetown University, University of Washington, and Stanford University School of Medicine. Falkow is known as the father of the field of molecular microbial pathogenesis. He formulated molecular Koch's postulates, which have guided the study of the microbial determinants of infectious diseases since the late 1980s. Falkow spent over 50 years uncovering molecular mechanisms of how bacteria cause disease and how to disarm them. Falkow also was one of the first scientists to investigate antimicrobial resistance, and presented his research extensively to scientific, government, and lay audiences explaining the spread of resistance from one organism to another, now known as horizontal gene transfer, and the implications of this phenomenon on our ability to combat infections in the future.
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.
Host tropism is the infection specificity of certain pathogens to particular hosts and host tissues. This explains why most pathogens are only capable of infecting a limited range of host organisms.
The Pathogen-Host Interactions database (PHI-base) is a biological database that contains manually curated information on genes experimentally proven to affect the outcome of pathogen-host interactions. The database has been maintained by researchers at Rothamsted Research and external collaborators since 2005. PHI-base has been part of the UK node of ELIXIR, the European life-science infrastructure for biological information, since 2016.
Microbiology is the scientific study of microorganisms, those being of unicellular (single-celled), multicellular, or acellular. Microbiology encompasses numerous sub-disciplines including virology, bacteriology, protistology, mycology, immunology, and parasitology.
Pathogenomics is a field which uses high-throughput screening technology and bioinformatics to study encoded microbe resistance, as well as virulence factors (VFs), which enable a microorganism to infect a host and possibly cause disease. This includes studying genomes of pathogens which cannot be cultured outside of a host. In the past, researchers and medical professionals found it difficult to study and understand pathogenic traits of infectious organisms. With newer technology, pathogen genomes can be identified and sequenced in a much shorter time and at a lower cost, thus improving the ability to diagnose, treat, and even predict and prevent pathogenic infections and disease. It has also allowed researchers to better understand genome evolution events - gene loss, gain, duplication, rearrangement - and how those events impact pathogen resistance and ability to cause disease. This influx of information has created a need for bioinformatics tools and databases to analyze and make the vast amounts of data accessible to researchers, and it has raised ethical questions about the wisdom of reconstructing previously extinct and deadly pathogens in order to better understand virulence.
Cause, also known as etiology and aetiology, is the reason or origination of something.
In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.
Lactococcus garvieae is a known fish pathogen affecting saltwater fish in the Far East, specifically in rainbow trout, Japanese yellowtail, Cobia and grey mullet. This bacteria causes lesions in the vascular endothelium, leading to hemorrhages and petechias at the surface of internal organs. As few as 10 bacterial cells per fish can cause an infection. L. garvieae is isolated in saltwater fish in the Far East and specifically in European rainbow trout.
Clinical metagenomic next-generation sequencing (mNGS) is the comprehensive analysis of microbial and host genetic material in clinical samples from patients by next-generation sequencing. It uses the techniques of metagenomics to identify and characterize the genome of bacteria, fungi, parasites, and viruses without the need for a prior knowledge of a specific pathogen directly from clinical specimens. The capacity to detect all the potential pathogens in a sample makes metagenomic next generation sequencing a potent tool in the diagnosis of infectious disease especially when other more directed assays, such as PCR, fail. Its limitations include clinical utility, laboratory validity, sense and sensitivity, cost and regulatory considerations.
Microbial pathogenesis is a field of microbiology that started at least as early as 1988, with the identification of the triune Falkow's criteria, aka molecular Koch's postulates. In 1996, Fredricks and Relman proposed a seven-point list of "Molecular Guidelines for Establishing Microbial Disease Causation," because of "the discovery of nucleic acids" by Watson and Crick "as the source of genetic information and as the basis for precise characterization of an organism." The subsequent development of the "ability to detect and manipulate these nucleic acid molecules in microorganisms has created a powerful means for identifying previously unknown microbial pathogens and for studying the host-parasite relationship."
Garth David Ehrlich is a molecular biologist, genomic scientist, academic, and author who is most known for his development of the distributed genome hypothesis and bringing the biofilm paradigm to the field of chronic mucosal bacterial diseases. He is a professor of Microbiology and Immunology, and Otolaryngology-Head and Neck Surgery at Drexel University. He is also the founder and executive director of three Research Centers of Excellence: the Center for Genomic Sciences (CGS); the Center for Advanced Microbial Processing (CAMP); and the Center for Surgical Infections and Biofilms. In addition, he serves as the executive director of the Genomics Core Facility and the director of Molecular Pathology within Drexel Medicine Diagnostics and the Sidney Kimmel Cancer Center's Meta-omics Core Facility.