Postulat adalah asumsi yang menjadi pangkal dalil yang dianggap benar tanpa perlu

membuktikannya. Postulat juga dapat dianggap sebagai anggapan dasar atau aksioma.
Postulat Koch dikenal juga sebagai postulat Henle’Koch, merupakan 4 kriteria yang
dirumuskan Robert Koch pada tahun 1884 dan diterbitkan di tahun 1890. Postulat Koch
berkembang pada abad ke-19 sebagai panduan umum untuk mengidentifikasi pathogen yang
dapay diisolasi dengan teknik tertentu.
Menurut Bollard (1993), pada tahun 1880, Koch memanfaatkan kemajuan metoda
laboratorium dan menentukan kriteria yang diperlukan untuk membuktikan bahwa mikroba
spesifik merupakan penyebab penyakit tertentu. Kriteria tersebut dikenal sebagai Postulat
Koch. Terdapat 4 kriteria yang dirumuskan, yaitu :

1. Mikroorganisme tertentu selalu ditemukan berasosiasi dengan penyakit yang

ditimbulkan.
2. Mikroorganisme dapat diisolasi dan ditumbuhkan sebagai biakan murni di
laboratorium.
3. Biakan murni tersebut bila diinjeksikan pada tanaman yang sesuai dapat menimbulkan
penyakit.
4. Mikroorganisme tersebut dapat diisolasi kembali dari tanaman yang telah terinfeksi
tersebut.

Keempat kriteria harus terpenuhi untuk menentukan sebab-musabab antara parasit dan
penyakit. Menurut Suada dan Suniti (2014), metode Postulat Koch dapat dilakukan untuk
membuktikan suatu patogen menyebabkan penyakit dengan menerapkan isolasi, inokulasi,
reisolasi, dan identifikasi mikroba yang berasosiasi. Setelah diketahui mikroba sebagai
penyebab maka kemudian mikroba tersebut diidentifikasi secara molekuler.

Postulat Koch dapat digunakan dan diterapkan pada berbagai bidang aplikatif  sesuai dengan
kebutuhannya masing-masing. Postulat Koch dapat diterapkan pada berbagai bidang,
diantaranya bidang mikrobiologi, bidang pertanian, bidang peternakan, dan bidang pangan.
Contoh penerapan postulat koch dalam bidang pertanian yaitu ketika terdapat serangn oleh
patogen pada pertanaman agroforestry, kemudian dalam bidang mikrobiologi dapat
digunakan untuk mengetahui peranan mikroba sebagai penyebab penyakit yang diterangkan
jelas dengan postulat tertentu (Saleh dan Nasir 2003).
In 1890, a German physicianand bacteriologist, Robert Koch set out his criteria for judging
whether a given bacteria is the cause of a given disease. Koch's criteria brought some much-
needed scientific clarity to what was then a very confused field.
Koch's postulates are as follows:

The bacteria must be present in every case of the disease.

The bacteria must be isolated from the host with the disease and grown in pure culture.
The specific disease must be reproduced when a pure culture of the bacteria is inoculated into
a healthy susceptible host.
The bacteria must be recoverable from the experimentally infected host.
However, Koch's postulates have their limitations and so may not always be the last word.
They may not hold if:

The particular bacteria (such as the one that causes leprosy) cannot be "grown in pure
culture" in the laboratory.
There is no animal model of infection with that particular bacteria.

A harmless bacteria may cause disease if:

It has acquired extra virulence factors making it pathogenic.

It gains access to deep tissues via trauma, surgery, an IV line, etc.
It infects an immunocompromised patient.
Not all people infected by a bacteria may develop disease-subclinical infection is usually
more common than clinically obvious infection.
Despite such limitations, Koch's postulates are still a useful benchmark in judging whether
there is a cause-and-effect relationship between a bacteria (or any other type of
microorganism) and a clinical disease.
Koch’s postulates are four criteria designed to establish a causal relationship
between a causative microbe and a disease. The postulates were formulated
by Robert Koch and Friedrich Loeffler in 1884 and refined and published by
Koch in 1890. Koch applied the postulates to establish the etiology of anthrax
and tuberculosis, but they have been generalized to other diseases.

Koch’s postulates were developed in the 19th century as general guidelines to

identify pathogens that could be isolated with the techniques of the day. Even
in Koch’s time, it was recognized that some infectious agents were clearly
responsible for disease even though they did not fulfill all of the postulates.
Attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases in
the late 19th century, at a time when viruses could not be seen or isolated in
culture, may have impeded the early development of the field of virology.
Currently, a number of infectious agents are accepted as the cause of disease
despite their not fulfilling all of Koch’s postulates. Therefore, while Koch’s
postulates retain historical importance and continue to inform the approach to
microbiologic diagnosis, fulfillment of all four postulates is not required to
demonstrate causality.
Koch’s postulates

Koch’s postulates are the following:

1. The microorganism must be found in abundance in all organisms suffering from the
disease, but should not be found in healthy organisms.
2. The microorganism must be isolated from a diseased organism and grown in pure
culture.
3. The cultured microorganism should cause disease when introduced into a healthy
organism.
4. The microorganism must be reisolated from the inoculated, diseased experimental
host and identified as being identical to the original specific causative agent.

Koch’s postulates have also influenced scientists who examine microbial

pathogenesis from a molecular point of view. In the 1980s, a molecular version of
Koch’s postulates was developed to guide the identification of microbial genes
encoding virulence factors.

Key Points
 The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and
refined and published by Koch in 1890.
  Postulate 1: The microorganism must be found in abundance in all organisms
suffering from the disease, but should not be found in healthy organisms.
 Postulate 2: The microorganism must be isolated from a diseased organism and
grown in pure culture.
 Postulate 3: The cultured microorganism should cause disease when introduced into
a healthy organism.
 Postulate 4: The microorganism must be reisolated from the inoculated, diseased
experimental host and identified as being identical to the original specific causative
agent.

Key Terms
 Koch’s postulates: four criteria designed to establish a causal relationship between
a causative microbe and a disease
 postulate: A fundamental element; a basic principle.
Robert Koch (1843-1910) was a German physician who helped establish bacteriology as a
science. Koch made important discoveries in identifying the bacteria that cause anthrax,
cholera, and tuberculosis, at ta time when the understanding of microbes was just emerging
Koch and his colleague, Friederich Loeffler developed a metho to identify a disease-causing
agent. Scientists today follow these basic principles, which we call Koch’s postuates, when
trying to identify the cause of an infectious disease. Koch’s postulates are based on careful
observations and reproducibility.

1st The microbe is present in each case of the disease

Koch developed these postulates while studying anthrax bacteria and tested them on mice. In
this case, the mice were standing in for the farm animals affected by the bacteria that cause
anthrax.
2nd The icrobe can be taken from the infected host and grown independently
Koch isolated and grew the bacteria in flat dishes invented by his colleagues Julius Richard
Petri. The dishes held a growth medium of agar ( a type of algae) and nutriens. Petri dishes
are still used by scientist today.
3rd The disease can be produced by introducing a pure culture of the microbe into a healthy
host
One exception to C is that some individuals may harbor disease-causing microbes and not
show signs of the disease. These are knowns as asymptomatic carriers.
4th The microbe can be isolated and identified from the host infected in step 3
By demonstrating that the anthrax bacteria grown in the culture were identical to the source
bacteria, Koch showed that the bacteria he observed were the cause of anthrax.
For two centuries, Koch’s postulates have set the gold standard for establishing the
microbiological etiology of infection and disease. Genomic sequencing now brings finer
resolution to both bacterial strain variation and the host genetic state that may predispose to
disease. In this issue of the JID, Fitz-Gibbons and colleagues present strain based resolution
of Propionibacterium acnes and its association with the common teenage malady acne
vulgaris. Here I examine how Koch’s postulates were envisioned and incorporate this finer
resolution of both host and microbial states.

Developed in the 19th century, Robert Koch’s postulates are the four criteria designed to
assess whether a microorganism causes a disease. As originally stated, the four criteria are:
(1) The microorganism must be found in diseased but not healthy individuals; (2) The
microorganism must be cultured from the diseased individual; (3) Inoculation of a healthy
individual with the cultured microorganism must recapitulated the disease; and finally (4)
The microorganism must be re-isolated from the inoculated, diseased individual and matched
to the original microorganism.

Koch’s postulates have been critically important in establishing the criteria whereby the
scientific community agrees that a microorganism causes a disease.

Even Koch had to modify or bend the strictest interpretation of the first postulate. Koch
discovered asymptomatic carriers of Vibrio cholera and Salmonella typhi, yielding the
important distinction between asymptomatic clinical colonization and infection. Thus the
field of inquiry into the intricate host-pathogen relationship was born.
Robert Koch (1843–1910) (Fig. 1-16C) was a medical doctor and a bacteriologist. He was the
first to show, in 1876, that anthrax, a disease of sheep and other animals, including humans,
was caused by a bacterium that he called Bacillus anthracis. He subsequently discovered, in
1882, that tuberculosis and, in 1883, that cholera are each caused by a different bacterium,
which led to the general conclusion that each disease is caused by a specific microbe. These
experiments confirmed for the first time the germ theory of disease proposed earlier by Louis
Pasteur.
Before Koch's experiments, and while Koch himself was carrying out the work on the
diseases mentioned earlier, there was confusion and uncertainty about the occurrence and the
cause of each disease. Much of the time when bacteria or fungi were isolated from diseased
or dead human, animal, or plant tissues, the isolated bacteria or fungi were subsequently
shown to be saprophytes, i.e., they coexisted with the microorganism that caused the disease
but could not by themselves cause the disease for which they were being considered. Based
on his experiences, in 1887, Koch set out the four steps or criteria that must be satisfied
before a microorganism isolated from a diseased human, animal, or plant can be considered
as the cause of the disease. These four steps, rules, or criteria are known as “Koch's
postulates.”
1.
The suspected causal agent (bacterium or other microorganism) must be present in
every diseased organism (e.g., a plant) examined.
2.
The suspected causal agent (bacterium, etc.) must be isolated from the diseased host
organism (plant) and grown in pure culture.
3.
When a pure culture of the suspected causal agent is inoculated into a healthy
susceptible host (plant), the host must reproduce the specific disease.
4.
The same causal agent must be recovered again from the experimentally inoculated
and infected host, i.e., the recovered agent must have the same characteristics as the
organism in step 2.
Koch's rules are possible to implement, although not always easy to
carry out, with such pathogens as fungi, bacteria, parasitic higher
plants, nematodes, most viruses and viroids, and the spiroplasmas.
These organisms can be isolated and cultured, or can be purified,
and they can then be introduced into the plant to see if they cause
the disease. With the other pathogens, however, such as some
viruses, phytoplasmas, fastidious phloem-inhabiting
bacteria, protozoa, and even some plant pathogenic fungi that are
obligate parasites of plants (such as the powdery mildew, downy
mildew, and rust fungi), culture or purification of the pathogen is not
yet possible and the pathogen often cannot be reintroduced into the
plant to reproduce the disease. Thus, with these pathogens, Koch's
rules cannot be carried out, and their acceptance as the actual
pathogens of the diseases with which they are associated is more
or less tentative. In most cases, however, the circumstantial
evidence is overwhelming, and it is assumed that further
improvement of techniques of isolation, culture, and inoculation of
pathogens will someday prove that today's assumptions are
justified. However, in the absence of the proof demanded by Koch's
rules and as a result of insufficient information, all plant diseases
caused by phytoplasmas (e.g., aster yellows) and fastidious
vascular bacteria (e.g., Pierce's disease of grape) were for years
thought to be caused by viruses.
Despite the difficulties of carrying out Koch's postulates with some
causal agents, they have been and continue to be applied,
sometimes with certain modifications, in all cases of disease. They
have had and continue to have a tremendous effect in deciding and
in convincing others that a particular microorganism is the cause of
a specific disease. By attempting to carry out Koch's postulates in
all newly discovered diseases, a great deal of work with potential
saprophytes has been avoided, while, at the same time, doubt and
criticism are reduced to a minimum while confidence in and use of
the identification increase greatly and quickly.

Koch's postulates were invaluable at the time they were developed and remain largely valid
for a relatively small number of defined circumstances in which bacteria can be precisely tied
to the cause of a particular clinical syndrome. But in a world in which viruses cause cancer
and noncultivable bacteria can be demonstrated by molecular probes, Koch's postulates are
no longer fit for purpose. What is more, used uncritically they have the potential to mislead.
Their main purpose now is to provide a framework to ensure that scientific rigor is applied
when proposing an organism as the cause of a disease – exactly as Koch intended when he
first conceived them.
Robert Koch's postulates, published in 1890, are a set of criteria that establish whether a
particular organism is the cause of a particular disease. Today, Koch's postulates are taught in
high school and college classrooms as a demonstration of the rigor and legitimacy of clinical
microbiology. To review, the four postulates of Koch are as follows:

–1.
The microorganism must be found in the diseased animal, and not found in healthy animals.

–2.
The microorganism must be extracted and isolated from the diseased animal and
subsequently grown in culture.

–3.
The microorganism must cause disease when introduced to a healthy experimental animal.

–4.
The microorganism must be extracted from the diseased experimental animal and
demonstrated to be the same microorganism that was originally isolated from the first
diseased animal.

Let's go over these four postulates once more, this time explaining how they ignore or
contradict what we now know about infectious diseases.

–1.
The microorganism must be found in the diseased animal, and not found in healthy animals.

As previously discussed, lots of pathogenic organisms are found in healthy animals,

producing disease in only a tiny fraction of the individuals who are infected. For example,
Bartonella species can live in blood without causing disease, producing an asymptomatic
bacteremia in the wide assortment of animals that they may infect. Hence, we can no longer
assume that blood samples from healthy animals are sterile. The mechanism of Bartonella
transmission from animal to animal is not fully understood, but arthropod vectors (ticks,
fleas, and lice) are suspected, as well as scratches and bites from infected animals (e.g., cats
and rats) [1] [Glossary Vector].
–2.
The microorganism must be extracted and isolated from the diseased animal (and grown in
culture).

Many pathogens do not grow in nutrient medium culture. This applies generally to common
Mollicute bacteria, including Erysipelothrix, Mycoplasma, and Ureoplasma. This would also
apply to viruses, none of which grow in cell-free media. Paradoxically, some of the
organisms known to produce bacteremias in human blood grow very poorly in blood cultures,
and this would include the aforementioned Bartonella species and the HACEK organisms [1,
3]. The HACEK organisms are a group of proteobacteria, found in otherwise healthy
individuals, that are known to cause some cases of endocarditis, especially in children, and
which do not grow well in culture. The term HACEK is created from the initials of the
organisms of the group: Haemophilus, particularly Haemophilus parainfluenzae;
Aggregatibacter, including Aggregatibacter actinomycetemcomitans and Aggregatibacter
aphrophilus; Cardiobacterium hominis; Eikenella corrodens; and Kingella, particularly
Kingella kingae.
–3.
The microorganism must cause disease when introduced to a healthy experimental animal.

Again, some of the worst microorganisms will not produce disease in healthy animals. To
confuse matters further, we now have examples of nonliving agents that will produce
transmissible disease in healthy animals (prions).

This third postulate of Koch presumes that each occurrence of an infectious disease has a
particular organism that is “the cause” of the disease. We must return here to our often-
repeated theme that diseases do not have “a cause,” and infectious diseases are no exception
to the rule that pathogenesis is a multistep process. We have already seen that myocardial
infarction results from a multitude of conditions that occur through time. In some cases, the
last event is infectious, wherein a focal bacterial endocarditis precipitates a thrombus that
blocks a narrowed coronary artery. It would be folly to believe that the sequence of events
that lead to a myocardial infarction can be precipitated simply by injecting an organism into
an animal. Later in this chapter, we will see two examples of rare infections for which several
conditions must prevail before a disease emerges [4, 5].
–4.
The microorganism must be extracted from the infected experimental animal and
demonstrated to be the same microorganism that was originally isolated from the original
diseased animal.
Many infections, considered the underlying cause of a disease, are absent from the lesions
that ultimately develop. For example, Group A streptococcus infection is considered to be the
underlying cause of rheumatic fever. The infection is long gone prior to the appearance of the
valvular and endocardial lesions of rheumatic fever. As another example, several species of
human papillomavirus are considered to be the underlying cause of nearly all cases of
squamous carcinoma of the uterine cervix. Morphologic cytopathic effects are visible in the
earliest precancers that precede the development of invasive carcinoma. The cancers, which
may occur years following the early papillomavirus infections, may lack recoverable virus.

Let's look at an example of an infectious disease that violates every one of Koch's postulates.
Whipple disease, previously a disease of unknown etiology, is characterized by organ
infiltration with foamy macrophages (i.e., specialized reticuloendothelial cells that “eat”
bacteria and debris). The organ most often compromised in Whipple disease is the small
intestine, where infiltration of infected macrophages in the lamina propria (i.e., a strip of
loose connective tissue subjacent to the epithelial lining of the small intestine) causes
malabsorption. Whipple disease is rare. It occurs most often in farmers and gardeners who
work with soil.
Whipple disease was first described in 1907 [6], but its cause was unknown until 1992, when
researchers isolated and amplified, from Whipple disease tissues, a 16s ribosomal RNA
sequence that could only have a bacterial origin [7]. Based on molecular features of the
ribosomal RNA molecule, the researchers assigned it to Class Cellulomonadacea, and named
the species Tropheryma whipplei, after the man who first described the disease, George Hoyt
Whipple.

Particularly noteworthy, in the case of Whipple disease, is that Koch's postulates never came
close to being satisfied. For the experimentalist, the most important of Koch's postulates
require the extraction of the organism from a lesion (i.e., from diseased, infected tissue), the
isolation and culture of the organism in the laboratory, and the consistent reproduction of the
lesion in an animal injected with the organism. In the case of Whipple disease, none of these
criteria were satisfied. The consistent identification in Whipple disease tissue of a particular
molecule, characteristic of a particular species of bacteria, was deemed sufficient to establish
the infectious origin of the disease.

In the general scheme of events, bacteria in the human body are eaten by macrophages,
wherein they are degraded. In the case of T. whipplei, only a small population of susceptible
individuals lack the ability to destroy T. whipplei organisms. In susceptible individuals, the
organisms multiply within macrophages. When organisms are released from dying
macrophages, additional macrophages arrive to feed, but this only result in the local
accumulation of macrophages bloated by bacteria. Whipple disease is a good example of a
disease caused by an organism but dependent on a genetic predisposition, expressed as a
defect in innate immunity; specifically, a reduction of macrophages expressing CD11b (also
known as macrophage-1 antigen) [8]. Whipple disease cannot be consistently reproduced in
humans or any other animals, because it can only infect and grow in a small portion of the
human population.
As we learn more and more about the complexity of disease causation, formerly useful
paradigms, such as Koch's postulates, seem burdensome and useless. When we encounter rare
diseases of infectious cause, we might expect to find that the pathogenesis of disease (i.e., the
biological steps that lead to a clinical phenotype) may require several independent causal
events to occur in sequence. In the case of Whipple disease, the infected individual must be
exposed to a soil organism, limiting the disease to farmers and gardeners. The organism,
residing in the soil, must be ingested, perhaps by the inhalation of dust. The organism must
evade degradation by gut macrophages, limiting disease to individuals with a specific type of
defect in cell-mediated immunity, and the individual must have disease that is sufficiently
active to produce clinical symptoms. It is unlikely that we could reproduce a complex
sequence of steps, leading to a disease, by simply inoculating an organism into an
experimental animal [Glossary Underlying cause, Proximate cause, Root cause].

Side-stepping Koch's postulates has become de rigueur in the practice of modern medicine.
For example, the United States has experienced a recent increase in cases of acute flaccid
myelitis, a rare disease of children [9]. Diagnosis is based on a metagenomic analysis (i.e.,
culture-independent sequence searches conducted on an assemblage of microbial gene
sequences in a biologic sample) of DNA obtained from nasopharyngeal swabs. The organism
that is present in most of the examined cases is enterovirus-D68, and this virus is the
presumed causal organism of acute flaccid myelitis, until proven otherwise.

Genotyping species of organisms has become quite easy, but there are many millions of
microorganism species, and it may never be feasible to complete a database of genome
sequences of all living species. Though the number of individual species is too large to
sequence, we can do a fair job at sequencing most of the different genera of living species.
We now have a fairly accurate way of identifying the genus of any organism found within a
tissue sample, by sequencing its ribosomal RNA and comparing the sequence against
references sequences in public databases [10–13]. There are limitations to this technique, but
when we combine our analysis of ribosomal RNA with our accumulated knowledge of
clinical features of the infection, we can often arrive at candidate pathogen [11, 14, 15].
Modern medicine has changed the vocabulary of infection. Familiar terms such as primary
pathogen, opportunistic infection, and immunocompetent patient need to be reexamined in
light of what we have come to know. Even a fundamental concept, such as “the organism
causing the disease” should probably be abandoned in light of the multistep pathogenesis of
all diseases. Because a microorganism may contribute to the pathogenesis of a disease at a
single moment of time, long before the disease becomes clinically manifest, we can expect to
see cases in which screening tests for a putative causal organism will be negative in affected
patients [16]. Koch, in his own time, understood the practical limitations of his postulates.
Maybe it's time to reconsider Koch's postulates in light of the analytic methods now available
that assign a taxonomic class to an infective organism, without isolating or characterizing the
agent [17].