A microbiologist examining cultures under a dissecting microscope.
Medical microbiology, the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases.
In addition, this field of science studies various clinical
applications of microbes for the improvement of health. There are four
kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.
A medical microbiologist studies the characteristics of pathogens, their modes of transmission, mechanisms of infection and growth. Using this information, a treatment can be devised. Medical microbiologists often serve as consultants for physicians,
providing identification of pathogens and suggesting treatment options.
Other tasks may include the identification of potential health risks to
the community or monitoring the evolution of potentially virulent
or resistant strains of microbes, educating the community and assisting
in the design of health practices. They may also assist in preventing
or controlling epidemics and outbreaks of disease.
Not all medical microbiologists study microbial pathology; some study common, non-pathogenic species to determine whether their properties can be used to develop antibiotics or other treatment methods.
Epidemiology, the study of the patterns, causes, and effects of health and disease
conditions in populations, is an important part of medical
microbiology, although the clinical aspect of the field primarily
focuses on the presence and growth of microbial infections in
individuals, their effects on the human body, and the methods of
treating those infections. In this respect the entire field, as an
applied science, can be conceptually subdivided into academic and
clinical sub-specialties, although in reality there is a fluid continuum
between public health microbiology and clinical microbiology, just as the state of the art in clinical laboratories depends on continual improvements in academic medicine and research laboratories.
History
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Anton van Leeuwenhoek was the first to observe microorganisms using a microscope.
In 1676, Anton van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design.
In 1796, Edward Jenner developed a method using cowpox to successfully immunize a child against smallpox. The same principles are used for developing vaccines today.
Following on from this, in 1857 Louis Pasteur also designed vaccines against several diseases such as anthrax, fowl cholera and rabies as well as pasteurization for food preservation.
In 1867 Joseph Lister is considered to be the father of antiseptic surgery. By sterilizing the instruments with diluted carbolic acid and using it to clean wounds, post-operative infections were reduced, making surgery safer for patients.
In the years between 1876 and 1884 Robert Koch provided much insight into infectious diseases. He was one of the first scientists to focus on the isolation of bacteria in pure culture. This gave rise to the germ theory,
a certain microorganism being responsible for a certain disease. He
developed a series of criteria around this that have become known as the
Koch's postulates.
A major milestone in medical microbiology is the Gram stain. In 1884 Hans Christian Gram
developed the method of staining bacteria to make them more visible and
differentiated under a microscope. This technique is widely used today.
In 1910 Paul Ehrlich tested multiple combinations of arsenic based chemicals on infected rabbits with syphilis.
Ehrlich then found that arsphenamine was found effective against
syphilis spirochetes. The arsphenamines was then made available in 1910,
known as Salvarsan.
In 1929 Alexander Fleming developed the most commonly used antibiotic substance both at the time and now: penicillin.
In 1939 Gerhard Domagk found Prontosil red protected mice from pathogenic streptococci and staphylococci without toxicity. Domagk received the Nobel Prize in physiology, or medicine, for the discovery of the sulfa drug.
DNA sequencing, a method developed by Walter Gilbert and Frederick Sanger in 1977, caused a rapid change the development of vaccines, medical treatments and diagnostic methods. Some of these include synthetic insulin which was produced in 1979 using recombinant DNA and the first genetically engineered vaccine was created in 1986 for hepatitis B.
In 1995 a team at The Institute for Genomic Research sequenced the first bacterial genome; Haemophilus influenzae. A few months later, the first eukaryotic genome was completed. This would prove invaluable for diagnostic techniques.
Commonly treated infectious diseases
Bacterial
Viral
Parasitic
Fungal
Causes and transmission of infectious diseases
Infections may be caused by bacteria, viruses, fungi, and parasites.
The pathogen that causes the disease may be exogenous (acquired from an
external source; environmental, animal or other people, e.g. Influenza) or endogenous (from normal flora e.g. Candidiasis).
The site at which a microbe enters the body is referred to as the portal of entry. These include the respiratory tract, gastrointestinal tract, genitourinary tract, skin, and mucous membranes. The portal of entry for a specific microbe is normally dependent on how it travels from its natural habitat to the host.
There are various ways in which disease can be transmitted between individuals.
These include:
- Direct contact - Touching an infected host, including sexual contact
- Indirect contact - Touching a contaminated surface
- Droplet contact - Coughing or sneezing
- Fecal–oral route - Ingesting contaminated food or water sources
- Airborne transmission - Pathogen carrying spores
- Vector transmission - An organism that does not cause disease itself but transmits infection by conveying pathogens from one host to another
- Fomite transmission - An inanimate object or substance capable of carrying infectious germs or parasites
- Environmental - Hospital-acquired infection (Nosocomial infections)
Like other pathogens, viruses use these methods of transmission to
enter the body, but viruses differ in that they must also enter into the
host's actual cells. Once the virus has gained access to the host's
cells, the virus' genetic material (RNA or DNA) must be introduced to the cell.
Replication between viruses is greatly varied and depends on the type
of genes involved in them. Most DNA viruses assemble in the nucleus
while most RNA viruses develop solely in cytoplasm.
The mechanisms for infection, proliferation, and persistence of a
virus in cells of the host are crucial for its survival. For example,
some diseases such as measles
employ a strategy whereby it must spread to a series of hosts. In these
forms of viral infection, the illness is often treated by the body's own immune response, and therefore the virus is required to disperse to new hosts before it is destroyed by immunological resistance or host death. In contrast, some infectious agents such as the Feline leukemia virus,
are able to withstand immune responses and are capable of achieving
long-term residence within an individual host, whilst also retaining the
ability to spread into successive hosts.
Diagnostic tests
Identification of an infectious agent for a minor illness can be as simple as clinical presentation; such as gastrointestinal disease
and skin infections. In order to make an educated estimate as to which
microbe could be causing the disease, epidemiological factors need to
be considered; such as the patient's likelihood of exposure to the
suspected organism and the presence and prevalence of a microbial strain
in a community.
Diagnosis of infectious disease is nearly always initiated by
consulting the patient's medical history and conducting a physical
examination. More detailed identification techniques involve microbial culture, microscopy, biochemical tests and genotyping. Other less common techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent.
Microbial culture
Four nutrient agar plates growing colonies of common Gram negative bacteria.
Microbiological culture
is the primary method used for isolating infectious disease for study
in the laboratory. Tissue or fluid samples are tested for the presence
of a specific pathogen, which is determined by growth in a selective or differential medium.
The 3 main types of media used for testing are:
- Solid culture: A solid surface is created using a mixture of nutrients, salts and agar. A single microbe on an agar plate can then grow into colonies (clones where cells are identical to each other) containing thousands of cells. These are primarily used to culture bacteria and fungi.
- Liquid culture: Cells are grown inside a liquid media. Microbial growth is determined by the time taken for the liquid to form a colloidal suspension. This technique is used for diagnosing parasites and detecting mycobacteria.
- Cell culture: Human or animal cell cultures are infected with the microbe of interest. These cultures are then observed to determine the effect the microbe has on the cells. This technique is used for identifying viruses.
Microscopy
Culture techniques will often use a microscopic examination to help in the identification of the microbe. Instruments such as compound light microscopes
can be used to assess critical aspects of the organism. This can be
performed immediately after the sample is taken from the patient and is
used in conjunction with biochemical staining techniques, allowing for
resolution of cellular features. Electron microscopes and fluorescence microscopes are also used for observing microbes in greater detail for research.
Biochemical tests
Fast and relatively simple biochemical tests can be used to identify infectious agents. For bacterial identification, the use of metabolic or enzymatic characteristics are common due to their ability to ferment carbohydrates in patterns characteristic of their genus and species. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media,
as mentioned above. In order to perform these tests en masse, automated
machines are used. These machines perform multiple biochemical tests
simultaneously, using cards with several wells containing different
dehydrated chemicals. The microbe of interest will react with each
chemical in a specific way, aiding in its identification.
Serological
methods are highly sensitive, specific and often extremely rapid
laboratory tests used to identify different types of microorganisms. The
tests are based upon the ability of an antibody to bind specifically to an antigen.
The antigen (usually a protein or carbohydrate made by an infectious
agent) is bound by the antibody, allowing this type of test to be used
for organisms other than bacteria. This binding then sets off a chain of
events that can be easily and definitively observed, depending on the
test. More complex serological techniques are known as immunoassays.
Using a similar basis as described above, immunoassays can detect or
measure antigens from either infectious agents or the proteins generated
by an infected host in response to the infection.
Polymerase chain reaction
Polymerase chain reaction (PCR) assays are the most commonly used molecular technique to detect and study microbes. As compared to other methods, sequencing and analysis is definitive, reliable, accurate, and fast. Today, quantitative PCR
is the primary technique used, as this method provides faster data
compared to a standard PCR assay. For instance, traditional PCR
techniques require the use of gel electrophoresis to visualize amplified DNA molecules after the reaction has finished. quantitative PCR does not require this, as the detection system uses fluorescence and probes to detect the DNA molecules as they are being amplified. In addition to this, quantitative PCR
also removes the risk of contamination that can occur during standard
PCR procedures (carrying over PCR product into subsequent PCRs).
Another advantage of using PCR to detect and study microbes is that the
DNA sequences of newly discovered infectious microbes or strains can be
compared to those already listed in databases, which in turn helps to
increase understanding of which organism is causing the infectious
disease and thus what possible methods of treatment could be used. This technique is the current standard for detecting viral infections such as AIDS and hepatitis.
Treatments
Once
an infection has been diagnosed and identified, suitable treatment
options must be assessed by the physician and consulting medical
microbiologists. Some infections can be dealt with by the body's own immune system, but more serious infections are treated with antimicrobial drugs. Bacterial infections are treated with antibacterials (often called antibiotics) whereas fungal and viral infections are treated with antifungals and antivirals respectively. A broad class of drugs known as antiparasitics are used to treat parasitic diseases.
Medical microbiologists often make treatment recommendations to the patient's physician based on the strain of microbe and its antibiotic resistances, the site of infection, the potential toxicity of antimicrobial drugs and any drug allergies the patient has.
Antibiotic
resistance tests: bacteria in the culture on the left are sensitive to
the antibiotics contained in the white, paper discs. Bacteria in the
culture on the right are resistant to most of the antibiotics.
In addition to drugs being specific to a certain kind of organism (bacteria, fungi, etc.), some drugs are specific to a certain genus or species
of organism, and will not work on other organisms. Because of this
specificity, medical microbiologists must consider the effectiveness of
certain antimicrobial drugs when making recommendations. Additionally, strains
of an organism may be resistant to a certain drug or class of drug,
even when it is typically effective against the species. These strains,
termed resistant strains, present a serious public health concern of
growing importance to the medical industry as the spread of antibiotic resistance worsens. Antimicrobial resistance is an increasingly problematic issue that leads to millions of deaths every year.
Whilst drug resistance typically involves microbes chemically
inactivating an antimicrobial drug or a cell mechanically stopping the
uptake of a drug, another form of drug resistance can arise from the
formation of biofilms.
Some bacteria are able to form biofilms by adhering to surfaces on
implanted devices such as catheters and prostheses and creating an extracellular matrix for other cells to adhere to.
This provides them with a stable environment from which the bacteria
can disperse and infect other parts of the host. Additionally, the
extracellular matrix and dense outer layer of bacterial cells can
protect the inner bacteria cells from antimicrobial drugs.
Medical microbiology is not only about diagnosing and treating
disease, it also involves the study of beneficial microbes. Microbes
have been shown to be helpful in combating infectious disease and
promoting health. Treatments can be developed from microbes, as
demonstrated by Alexander Fleming's discovery of penicillin as well as the development of new antibiotics from the bacterial genus Streptomyces among many others. Not only are microorganisms a source of antibiotics but some may also act as probiotics to provide health benefits to the host, such as providing better gastrointestinal health or inhibiting pathogens.
