Medical microbiology

Source: Wikipedia, the free encyclopedia.
A microbiologist examining cultures under a dissecting microscope.

Medical microbiology, the large subset of

fungi, parasites and viruses, and one type of infectious protein called prion
.

A medical

physicians
, providing identification of pathogens and suggesting treatment options. Using this information, a treatment can be devised. Other tasks may include the identification of potential health risks to the community or monitoring the evolution of potentially
epidemics
and outbreaks of disease. Not all medical microbiologists study microbial
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

Anton van Leeuwenhoek
was the first to observe microorganisms using a microscope.
Statue of Robert Koch, father of medical bacteriology,[2] at Robert-Koch-Platz (Robert Koch square) in Berlin

In 1676,

Anton van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design.[3]

In 1796,

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.[5]

In 1867

carbolic acid and using it to clean wounds, post-operative infections were reduced, making surgery safer for patients.[6]

In the years between 1876 and 1884

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.[7]

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.[8]

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.[9]

In 1929 Alexander Fleming developed one of the most commonly used antibiotic substances both at the time and now: penicillin.[10]

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.[9]

DNA sequencing, a method developed by Walter Gilbert and Frederick Sanger in 1977,[11] 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

eukaryotic genome was completed. This would prove invaluable for diagnostic techniques.[13]

In 2007, a team at the Danish food company Danisco, were able to identify the purpose of the CRIPR-Cas systems as adaptive immunity to phages. The system was then quickly found to be able to help in genome editing through its ability to generate double strand breaks. A patient with sickle cell disease was the first person to be treated for a genetic disorder with CRISPR in July 2019.[14]

Commonly treated infectious diseases

Bacterial

Viral

Parasitic

Fungal

Causes and transmission of infectious diseases

Infections may be caused by

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).[27]

The site at which a microbe enters the body is referred to as the portal of entry.

mucous membranes.[29] The portal of entry for a specific microbe is normally dependent on how it travels from its natural habitat to the host.[28]

There are various ways in which disease can be transmitted between individuals. These include:[28]

  • 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.[30][31]

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.[32] 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.[33]

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

NMR
) are used to produce images of internal abnormalities resulting from the growth of an infectious agent.

Microbial culture

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:[34]

  • 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
    mycobacteria.[35]
  • 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

Electron microscopes and fluorescence microscopes are also used for observing microbes in greater detail for research.[36] The two main types of electron microscopy are scanning electron microscopy and transmission electron microscopy. Transmission electron microscopy passes electrons through a thin cross-section of the cell of interest, and it then redirects the electrons onto a fluorescent screen. This method is useful for looking at the inside of cells, and the structures within, especially cell walls and membranes. Scanning electron microscopy reads the electrons that are reflected off the surface of the cells. A 3-dimensional image is then made which shows the size and exterior structure of the cells. Both techniques help give more detailed information about the structure of microbes. This makes it useful in many medical fields, such as diagnostics and biopsies of many body parts, hygiene, and virology. They provide critical information about the structure of pathogens, which allow physicians to treat them with more knowledge.[37]

Biochemical tests

Fast and relatively simple

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.

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.[34]

Polymerase chain reaction

.

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

parasitic diseases
.

Medical microbiologists often make treatment recommendations to the patient's physician based on the strain of

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

antibiotic resistance worsens. Antimicrobial resistance is an increasingly problematic issue that leads to millions of deaths every year.[41]

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.[42] 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.[43]

Phage therapy is a technique that was discovered before antibiotics, but fell to the wayside as antibiotics became predominate. It is now being considered as a potential solution to increasing antimicrobial resistance. Bacteriophages, viruses that only infect bacteria, can specifically target the bacteria of interest and inject their genome. This process makes the bacteria halt its own production to make more phages, and this continues until the bacteria lyses itself and releases the phages into the surrounding environment. Phage therapy does not kill microbiota since it is specific, and it can help those with antibiotic allergies. Some drawbacks are that it is a time-intensive process since the specific bacterium needs to be identified. It also does not currently have the body of research supporting its effects and safety that antibiotics do. Bacteria can also eventually become resistant, through systems like CRISPR/Cas9 system. Many clinical trials have been promising though, showing that it could potentially help with the antimicrobial resistance problem. It can also be used in conjunction with antibiotics for a cumulative effect.[44]

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

probiotics to provide health benefits to the host, such as providing better gastrointestinal health or inhibiting pathogens.[46]

References

  1. .
  2. .
  3. .
  4. .
  5. .
  6. .
  7. .
  8. .
  9. ^ .
  10. .
  11. ^ Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors" Proceedings of the National Academy of Sciences 74:5463-5467.
  12. ^ Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A, Bult C, Tomb J, Dougherty B, Merrick J, al. e (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd" Science 269:496-512.
  13. ^ Prescott LM, Harley JP, Klein DA (2005) Microbiology: McGraw-Hill Higher Education.
  14. ^ (Stein 2019) (Barrangou & Horvath 2017)
  15. from the original on 2015-10-28.
  16. .
  17. ^ "Typhoid Fever". World Health Organization. Archived from the original on 2011-11-02. Retrieved 2013-04-25.
  18. ^ a b "World Health Statistics 2012". World Health Organization. Archived from the original on 2013-04-20. Retrieved 2013-04-25.
  19. PMID 22789574
    .
  20. ^ "Hepatitis C". World Health Organization. Archived from the original on 2011-07-12. Retrieved 2013-04-25.
  21. PMID 17327523
    .
  22. .
  23. ^ "Toxoplasmosis". Centers for Disease Control and Prevention. Archived from the original on 2013-04-25. Retrieved 2013-04-25.
  24. ^ "Candidiasis". Centers for Disease Control and Prevention. Archived from the original on 2013-04-19. Retrieved 2013-04-25.
  25. ^ "Histoplasmosis". Centers for Disease Control and Prevention. Archived from the original on 2013-05-03. Retrieved 2013-04-25.
  26. S2CID 20445682
    .
  27. PMID 21413287. Archived from the original
    on 13 June 2016.
  28. ^ .
  29. .
  30. ^ Roberts RJ, "Fish pathology, 3rd Edition", Elsevier Health Sciences, 2001.
  31. PMID 21413311. Archived from the original
    on 11 May 2018.
  32. .
  33. .
  34. ^ .
  35. .
  36. ^ Madigan MT (2009) Brock Biology of Microorganisms: Pearson/Benjamin Cummings.
  37. ^ (Boseck 1982) (Slonczewski & Foster 2017)
  38. ^ .
  39. ^ .
  40. .
  41. ^ WHO (April 2014). "Antimicrobial resistance: global report on surveillance 2014". WHO. Archived from the original on May 15, 2015. Retrieved May 9, 2015.
  42. ^ Vickery K, Hu H, Jacombs AS, Bradshaw DA, Deva AK (2013) A review of bacterial biofilms and their role in device-associated infection. Healthcare Infection .
  43. S2CID 46125592
    .
  44. ^ (Gordillo Altamirano & Barr 2019) (Kortright et al. 2019)
  45. ^ Taguchi T, Yabe M, Odaki H, Shinozaki M, Metsä-Ketelä M, Arai T, Okamoto S, Ichinose K (2013) Biosynthetic Conclusions from the Functional Dissection of Oxygenases for Biosynthesis of Actinorhodin and Related Streptomyces Antibiotics. Chemistry & Biology 20:510-520.
  46. ^ Williams NT (2010) Probiotics. American Journal of Health-System Pharmacy 67:449-458.

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