Introduction to Microbiology

A Brief History of Microbiology

•

Development of microscopy:

• 1590: Hans ( 漢司 ) and Zacharias Janssen ( 詹森 ) (Dutch lens grinders) mounted two lenses in a tube to produce the first compound microscope . • 1660: Robert Hooke ( 虎克 ) (1635-1703) published "Micrographia", containing drawings and detailed observations of biological materials made with the best compound microscope and illumination system of the time .

• 1676: Anton van Leeuwenhoek ( 劉文虎克 ) (1632-1723, Holland) was the first person to observe microorganisms . • 1883: Carl Zeiss ( 蔡斯 ) (German maker of optical instruments) and Ernst Abbe ( 艾比 ) (German physicist, optometrist, entrepreneur, and social reformer ) pioneered developments in microscopy (such as oil immersion lenses ( 油浸 鏡 )and apochromatic ( 複消色差 ) lenses which reduce chromatic aberration[ 色差 ]) which persist until the present day.

• 1931: Ernst Ruska ( 盧思卡 ) (German physicist who won the Nobel Prize in Physics in 1986) constructed the first electron microscope .#

Spontaneous generation controversy

• 1688: Francesco Redi ( 瑞迪 ) (1626-1678) was an Italian physician who refuted the idea of spontaneous generation by showing that rotting meat carefully kept from flies will not spontaneously produce maggots. • 1836: Theodor Schwann ( 許旺 ) (1810-1882) helped develop the cell theory of living organisms, namely that that all living organisms are composed of one or more cells and that the cell is the basic functional unit of living organisms.

• • • • 1861: Louis Pasteur‘s ( 巴斯德 ) (1822 1895) famous experiments with swan necked flasks finally proved that microorganisms do not arise by spontaneous generation.

This eventually led to: Development of sterilization ( 消毒 ) Development of aseptic technique # ( 無菌 )

Proof that microbes cause disease

• 1546: Hieronymus Fracastorius ( 法拉科斯 特 ) (Girolamo Fracastoro) (Italian physician, poet, and scholar in mathematics, geography and astronomy) wrote "On Contagion" ( 接觸傳染 ) ("De contagione et contagiosis morbis et curatione"), the first known discussion of the phenomenon of contagious infection .

• 1835 Agostino Bassi de Lodi ( 羅迪 ) (Italian entomologist) showed that a disease affecting silkworms was caused by a fungus - the first microorganism to be recognized as a contagious agent of animal disease .

• 1847: Ignaz Semmelweiss ( 森梅威斯 ) (1818-1865), a Hungarian physician who decided that doctors in Vienna hospitals were spreading childbed fever while delivering babies. He started forcing doctors under his supervision to wash their hands before touching patients. • 1857: Louis Pasteur ( 巴斯德 ) proposed the “ germ theory ” of disease ( 疾病的病菌學說 ).

• 1867: Joseph Lister ( 李斯特 ) (1827-1912) (British surgeon) introduced antiseptics ( 無菌 ) in surgery. By spraying carbolic acid ( 石炭酸 , phenol, 使細菌細胞的原生質 蛋白發生凝固或變性而殺菌 ) on surgical instruments, wounds and dressings, he reduced surgical mortality due to bacterial infection considerably.

• 1876: Robert Koch ( 寇赫 ) (1843-1910). German bacteriologist was the first to cultivate anthrax ( 炭疽 ) bacteria outside the body using blood serum at body temperature. Building on pasteur‘s “germ theory”, he subsequently published “

Koch’s postulates

” ( 寇赫假說 ) (1884), the critical test for the involvement of a microorganism in a disease:

炭疽病 •形容感染者皮膚上焦黑的損傷病變 •一種人畜共通病 ，炭疽可透過消化道、呼 吸道、皮膚接觸等途徑進入人體 困難、脾臟腫脹等症狀。 ， 人感染 後，則發生皮膚膿疱、咳嗽、吐痰、呼吸 •肺（呼吸）和腸胃炭疽病不治療 致死率達 100% 。 •皮膚炭疽病不加以治療卻仍有20%的致死率， 治療後幾乎不會有危險。

• The agent must be present in every case of the disease. • The agent must be isolated and cultured in vitro. • The disease must be reproduced when a pure culture of the agent is inoculated into a susceptible host. • The agent must be recoverable from the experimentally-infected host.

• This eventually led to: • Development of pure culture ( 純種培養 ) techniques • Stains ( 染色 ), agar ( 洋菜 ), culture media ( 培養基 ), petri dishes ( 培養皿 ) #

Microbial Pathogenesis

•

What does a pathogen have to do?

• Infect (infest) a host • Reproduce (replicate) itself • Ensure that its progeny are transmitted to another host

Mechanisms of Transmission(

傳染

)

• • • •

Aerosols

( 氣溶膠 )- inhalation of droplets, e.g. Rhinoviruses ( 鼻病毒 ), the 'Common Cold Virus' or Adenoviruses ( 腺病毒 ).

Faecal-Oral

( 糞便 )- e.g. Astroviruses ( 星狀病毒 ), Caliciviruses ( 嵌杯樣病毒 ); these viruses cause acute gastroenteritis ( 胃腸炎 ).

Vector-borne

( 媒介 )- e.g. in Arthropods such as mosquitos, ticks ( 壁蝨 ), fleas: Arboviruses ( 蟲 媒病毒 ).

Close personal contact

exchange of bodily fluids: Sex; Blood, e.g. Herpesviruses ( 皰疹病毒 ( 親密接觸 ). # )- especially

• Generally today, the all-encompassing group of “microbes” are divided into viruses ( 病毒 ), bacteria ( 細菌 ), fungi ( 真菌 ), and protozoans ( 原生動物 ).

Viruses

• Viruses are the simplest organisms we are aware of. They are essentially nucleic acid ( 核酸 ) (viruses can have genomes consisting of either DNA or RNA ) wrapped in a protein coat .

• On their own, viruses are incapable of any metabolism, including replication. However, viruses contain proteins on their surface which facilitate binding to and entry into cells of every type imaginable, from bacteria to human cells .

• A single cell may produce anywhere from 10,000 to 50,000 new viruses in as little as 48 hours’ time.

• Diseases caused by viruses include influenza, the common cold, herpes ( 皰疹 ), Ebola, and AIDS.

埃博拉 （

Ebola

） •一群屬於纖維病毒科埃博拉病毒屬下數種 病毒的通用術語，可導致埃博拉病毒出血 熱此病可致人於死，包含數種不同程度的 症狀，包括噁心、嘔吐、腹瀉、膚色改變、 全身痠痛、體內出血、體外出血、發燒等， 具有50%至90%的致死率，致死原因主要為 中風、心肌梗塞、低血容量休克或多發性 器官衰竭。

•此病毒以非洲剛果民主共和國的 埃博拉河命名 （該國舊稱薩伊） •埃博拉是人畜共通病毒，通常藉由體液、黏膜、 皮膚等接觸造成感染。 •至今仍沒有辨認出任何有能力在爆發時存活的動 物宿主，目前認為 果蝠 是病毒可能的原宿主 •因為埃博拉的致命力，加上目前 尚未有任何疫苗 被證實有效，埃博拉被列為生物安全第四級病毒

Flu and Common cold

• The common cold eventually fizzles ( 消退 ), but the flu may be deadly.

• The flu is caused by the influenza virus, a respiratory virus and is preventable with vaccination ( 疫苗 ) . • The common cold is caused by the adenovirus or coronavirus ( 冠狀病毒 ) and there are many, many subsets with a lot of variability.

• Flu causes epidemics and pandemics (covers a much wider geographical area, often worldwide.) with the potential for mortality , whereas the common cold is a nuisance ( 騷擾行為 ) for us. • Both colds and flu usually last the same seven to 10 days, but flu can go three to four weeks ; the flu virus may not still be there, but you have symptoms long after it's left.

Bacteria

• Bacteria are single-celled organisms which populate almost every niche on earth, from the hottest springs and chilliest waters to many spaces on and within the human body. As a group they are extremely diverse in size, shape, motility, nutrient requirements and pathogenicity (ability to cause disease), but share the common trait of lacking a true nucleus (and hence are referred to as “prokaryotic” ， 原核生物 ).

• Though most of the earliest bacteria discovered were pathogens (disease causing organisms), the vast majority of bacteria on earth are harmless , or even helpful, to humans. Many animals rely on gut bacteria to provide nutrients from food, which we are unable to synthesize ourselves (for example,

E. coli

( 大腸菌 ) in the gut produce Vitamin K ).

• Additionally, commensal ( 共生 ) (non pathogenic) bacteria fill niches in our body and use resources that would otherwise be available to other pathogenic microorganisms.

• Diseases caused by bacteria include tuberculosis ( 結核病 ) (

Mycobacterium tuberculosis

), “Black Plague,” ( 黑死病 ) (

Yersinia pestis

), strep throat ( 鏈球菌性 喉炎 ) (

Streptococcus pyogenes

), and syphilis ( 梅毒 ) (

Treponema pallidum

).

Protozoans

• Protozoans are single-celled, eukaryotic ( 真核生物 ) organisms belonging to the kingdom Protista. This means that, like human cells, they have a true nucleus. Most protozoa are motile as well, and are often fairly large for a single-celled organism (generally 1-100 microns in size, although some can be up to 1 millimeter in length).

• Diseases caused by protozoa include: malaria ( 瘧疾 ) (

Plasmodium falciparum

), sleeping sickness (

Trypanosoma cruzi

) ( 非 洲錐蟲病 ), amoebic dysentery (

Entamoeba histolytica

) ( 阿米巴痢疾 ).

Fungi

• Fungi are also eukaryotic, and include organisms such as molds and yeasts . Approximately 100 fungal species (out of ~100,000 known) are pathogenic for man. Yeasts are superficially similar to bacteria, in that they are unicellular and generally divide by simple binary fission (one cell divides into two).

• Molds, on the other hand, generally have complex life cycles during which they pass through both an asexual and a sexual stage. They exist as multicellular organisms during much of this period, and at this point, are far from being “micro” organisms. Nevertheless, because it is often their (microscopic) spores ( 孢子 ) which are responsible for diseases, they remain classed as general “microbes.”

• Diseases caused by fungi include thrush ( 黴菌性口炎,鵝口瘡 ) and yeast infections of candida ( 假絲酵母 ) and thrush in babies, and ringworm ( 金錢癬 )/athlete’s foot (various species).###

immune system

• many of the symptoms of an infectious disease are due to responses of the immune system . Fever, for example, is due to the production of proteins called cytokines ( 細胞因子 ) in response to an infectious agent. Cytokines serve to dilate ( 膨脹 ) the blood vessels, allowing blood cells to seep out of the capillaries and into the tissue. This causes the typical red flush of a fever.

• Fluid also is released from the vessels, causing swelling; and proteins called pyrogens ( 致熱源 ) (“fever-producers”) act on the brain to increase the body’s rate of metabolism, raising its temperature to one incompatible with the growth of many pathogenic agents. Thus, while we see fever as a symptom, it is actually a carefully controlled evolutionary response to dealing with infectious agents.

• The real workhorses of the immune system, however, are the cells collectively referred to as white blood cells . The primary defense is provided by a group of cells termed phagocytes (“eater cell”) ( 吞 噬細胞 ). Their job is to engulf and destroy debris, which includes foreign organisms and proteins.

• The other key warriors of our immune system are the B and T lymphocytes. These cells are critical to immune function. B cells produce and release proteins called antibodies, which circulate in the blood, recognizing and bind to invading pathogens, targeting them for destruction and elimination.

• T cells, on the other hand, recognize host cells that are expressing abnormal proteins; this includes cells infected by viruses or other foreign agents. They then target these cells for killing by phagocytes or other mechanisms.

• As a general rule, B cells (and the antibodies they produce) are most important when dealing with bacterial, protozoa or fungal infections; T cells, on the other hand, are most important when fighting a viral infection.

Last words

• Finally, while the immune system is critically important in fighting disease, it is important to take into consideration simple physical barriers as well. The first and most important is the skin; when unbreached, it provides an excellent first line of defense against offending microorganisms.

• A second line of defense is the mucus layer, which coats most of our internal epithelium (the layer of cells covering all surfaces of the body). This works both to physically trap microorganisms, as well as to kill them due to the presence of antimicrobial substances in the mucus.

• Other barriers include the acidity of the stomach, which kills greater than 99% of all organisms ingested; and ciliated cells (a type of cells which contain a specialized flagellum) which line our lungs, to aid in expelling microorganisms from the body.

• Finally, as mentioned above, commensal ( 共生的 ) organisms cover many spaces on and within our body, using nutrients and taking physical space away from any potential harmful invaders.###