Bringing Koch's postulates to the table in IBD

In this issue of Cell Host & Microbe, Bloom and colleagues elegantly show that commensal Bacteroides species fulfill Koch's postulates for inflammatory bowel disease in a host-genotype-specific way. This study showcases the use of a non-germ-free mouse model to identify specific members of the microbiota involved in disease development.     

A spirit of scientific rigour: Koch's postulates in twentieth-century medicine

This article explores one of a citation classics in medical literature—Koch's postulates. It analyses their creation in the nineteenth century and their popularity in the twentieth century. As a genre of historiography, references to the postulates are anecdotes. In referring to a historical event that never happened, such references serve to remind their audiences of a tradition of experimental medicine that supposedly originated with Robert Koch.     

Koch's postulates and the etiology of AIDS: an historical perspective.

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.     

Molecular Koch's postulates applied to bacterial pathogenicity--a personal recollection 15 years later

Koch's postulates were derived from Robert Koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day. These guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease. They were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a microorganism and a disease.     

The unconventional geminivirus Beet curly top Iran virus: satisfying Koch's postulates and determining vector and host range

Beet curly top Iran virus (BCTIRV) is a geminivirus with unusual genomic organisation, recently reported in Iran, infecting sugarbeet and a few other plant species. Although three BCTIRV sequences have been reported, demonstration that BCTIRV DNA is the causal agent of the disease was missing. A full‐length genomic DNA was obtained from symptomatic leaves of sugarbeet collected in the Sivand area of Iran, and its nucleotide sequence was determined (BCTIRV‐Siv, 2845 nt). To satisfy Koch's postulates, an infectivity assay was developed by inserting a 1.4‐mer of BCTIRV‐Siv DNA in Agrobacterium tumefaciens and using it in agroinoculation experiments. The cloned viral DNA was capable of infecting sugarbeets, reproducing the leaf curling and vein enations observed in the field. These results demonstrate that the single DNA component of BCTIRV is sufficient for infectivity. Host range studies indicated that some economically important crops can be affected, such as spinach, tomato and sweet pepper, as well as important laboratory plants including Nicotiana benthamiana, Arabidopsis thaliana and Jimson weed. Circulifer haematoceps, the dominant leafhopper species present in sugarbeet fields in Iran, was successfully used to transmit the disease. The availability of an infectious clone will facilitate extended host range studies, to determine the potential risks to other crops, as well as genetic studies on this unusual member of the family Geminiviridae.     

Polymicrobial challenges to Koch's postulates: Ecological lessons from the bacterial vaginosis and cystic fibrosis microbiomes

Koch's postulates have shaped our understanding of infectious diseases; however, one of the tangential consequences of them has been the emergence of a predominantly monomicrobial perspective concerning disease aetiology. This orthodoxy has been undermined by the growing recognition that some important infectious diseases have a polymicrobial aetiology. A significant new development in our understanding of polymicrobial infections is the recognition that they represent functional ecosystems and that to understand such systems and the outcome and impact of therapeutic interventions requires an understanding of how these communities arise and develop. Therefore, it is timely to explore what we can learn from other fields. In particular, ecological theory may inform our understanding of how polymicrobial communities assemble their structure and their dynamics over time. Such work may also offer insights into how such communities move from stable to unstable states, as well as the role of invasive pathogens in the progression of the disease. Ecological theory offers a theoretical framework around which testable hypotheses can be developed to clarify the polymicrobial nature and dynamics of such infections in the face of environmental change and therapeutic interventions.     

In vitro cultured Neoparamoeba perurans causes amoebic gill disease in Atlantic salmon and fulfils Koch's postulates

Amoebic gill disease (AGD) in marine farmed Atlantic salmon is of growing concern worldwide and remains a significant health issue for salmon growers in Australia. Until now the aetiological agent, Neoparamoeba perurans, has not been amenable to in vitro culture and therefore Koch's postulates could not be fulfilled. The inability to culture the amoeba has been a limiting factor in the progression of research into AGD and required the maintenance of an on-going laboratory-based infection to supply infective material. Culture methods using malt yeast agar with sea water overlaid and subculturing every 3-4 days have resulted in the establishment of a clonal culture of N. perurans, designated clone 4. Identity of the amoeba was confirmed by PCR. After 70 days in culture clone 4 infected Atlantic salmon, causing AGD, and was re-isolated from the infected fish. Diagnosis was confirmed by histology and the infectious agent identified by PCR and in situ hybridisation using oligonucleotide primers and probes previously developed and specific to N. perurans. This study has fulfilled Koch's postulates for N. perurans as a causative agent of AGD and illustrates its free-living and parasitic nature.     

Sweepoviruses cause disease in sweet potato and related Ipomoea spp.: fulfilling Koch's postulates for a divergent group in the genus begomovirus

Sweet potato (Ipomoea batatas) and related Ipomoea species are frequently infected by monopartite begomoviruses (genus Begomovirus, family Geminiviridae), known as sweepoviruses. Unlike other geminiviruses, the genomes of sweepoviruses have been recalcitrant to rendering infectious clones to date. Thus, Koch's postulates have not been fullfilled for any of the viruses in this group. Three novel species of sweepoviruses have recently been described in Spain: Sweet potato leaf curl Lanzarote virus (SPLCLaV), Sweet potato leaf curl Spain virus (SPLCSV) and Sweet potato leaf curl Canary virus (SPLCCaV). Here we describe the generation of the first infectious clone of an isolate (ES:MAL:BG30:06) of SPLCLaV. The clone consisted of a complete tandem dimeric viral genome in a binary vector. Successful infection by agroinoculation of several species of Ipomoea (including sweet potato) and Nicotiana benthamiana was confirmed by PCR, dot blot and Southern blot hybridization. Symptoms observed in infected plants consisted of leaf curl, yellowing, growth reduction and vein yellowing. Two varieties of sweet potato, 'Beauregard' and 'Promesa', were infected by agroinoculation, and symptoms of leaf curl and interveinal loss of purple colouration were observed, respectively. The virus present in agroinfected plants was readily transmitted by the whitefly Bemisia tabaci to I. setosa plants. The progeny virus population present in agroinfected I. setosa and sweet potato plants was isolated and identity to the original isolate was confirmed by sequencing. Therefore, Koch's postulates were fulfilled for the first time for a sweepovirus.     

Fulfilment of Koch's postulates and preliminary host range results for Septoria lepidii,a fungal pathogen for potential biological control of hoary cress (Lepidium spp.)

Koch's postulates were fulfilled on five geographical accessions of Lepidium draba and preliminary host range tests were conducted with Septoria lepidii Desm. on 42 Brassicaceae species. Host range results showed the fungus specific to Lepidium spp. This fungus is potentially an important biological control agent for weedy species of Lepidium.