Chapter 30. Examples of Major Microorganisms
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1. Virus
2. Bacteria
3. Archaea
4. Fungi
5. Protists
a. Biological Weapons in Chemical Warfare
b. Countermeasures against Biological Terrorism
c. Effective Disinfectants in Biological Action
1. Virus
● Overview
○ Viruses cannot be classified as Gram-positive or Gram-negative.
○ Gram staining is a concept applicable only to bacteria with peptidoglycan.
○ Types of Viruses
Figure 1. Types of Viruses
● Adenovirus (AdV)
○ 36 kb, dsDNA virus, naked virus
○ Helper-dependent parvovirus
○ Small (18-25 nm) icosahedral capsid
○ DNA structure : ITR - REP - CAP - ITR
○ ITR (inverted terminal repeat) : Unique cis element required for REP·CAP
○ REP : Responsible for replication
○ CAP : Responsible for packaging
○ Adenovirus enters cells through clathrin-mediated endocytosis.
● Coronavirus (CoV) : Member of Nidovirales
○ Characteristics : Enveloped virus
○ Genetic Material : Positive-sense single-stranded RNA
○ Helical symmetry nucleocapsid
○ Mechanism : Infects respiratory system in humans
○ Symptoms : Usually asymptomatic, but can cause severe symptoms at times
○ Classification : Alpha (Group Ⅰ), Beta (Group Ⅱ), Gamma (Group Ⅲ), Delta (Group Ⅳ)
○ Example 1. SARS (Severe Acute Respiratory Syndrome)
○ The virus causing SARS is referred to as SARS-CoV.
○ Occurred in winter 2002 in China.
○ Example 2. MERS (Middle East Respiratory Syndrome)
○ Disease caused by a novel coronavirus (nCoV)
○ Infects only ciliated epithelial cells
○ First appeared in Saudi Arabia in April 2012, believed to be transmitted by camels or bats
○ First case in South Korea in May 2015
○ Declared the end of MERS by WHO on September 17, 2018
○ Example 3. Novel Coronavirus (COVID-19) : Refer below
● Additional Information : Novel Coronavirus (2019-nCoV, COVID-19)
○ Overview
○ Caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)
○ First appeared in Wuhan, China in December 2019
○ As of July 9, 2020, more than 540,000 deaths have occurred
○ Characteristics
○ Enveloped virus
○ Approximately 80-120 nm
○ About 40,000 kDa
○ Components
○ Component 1: Spike (S) protein : Around 100 copies
○ Length of about 20 nm. Subdivided into S1 subunit and S2 subunit
○ 75 spikes on the surface of coronavirus
○ Component 2: Envelope (E) protein : Around 20 copies
○ Component 3: Membrane (M) protein : Around 2000 copies
○ Component 4: Nucleocapsid (N) protein : Around 1000 copies. Protein shell with a coil shape surrounding the genome
○ Helical symmetry nucleocapsid
○ 1-1. S1 subunit : Trimer
○ Performs host cell-specific binding : Kd value of binding with ACE2 is about 15 nM (quite large)
○ S1-NTD and S1-CTD in the S1 subunit are receptor-binding domains
○ S1-CTD : Binds to ACE2, APN (aminopeptidase N), DPP4 (dipeptidyl peptidase 4)
○ 1-2. S2 subunit
○ Connects S1 unit and virus cell membrane
○ 1-3. S1 and S2 subunits of coronavirus are separated by host cell proteases
○ Involvement of cathepsin family and TMPRSS2 (transmembrane protease serine 2)
○ Life Cycle (Hartenian et al., 2020)
○ Phase 1: Binding and viral entry via membrane fusion or endocytosis
○ Phase 2: Translation of polypeptide
○ Phase 3: Autoproteolysis and co-translational cleavage of polypeptide to generate nsps (non-structural proteins)
○ Phase 4: (-sense) Subgenomic transcription and RNA replication
○ Phase 5: (+sense) Subgenomic transcription and RNA replication
○ Phase 6: Translation of subgenomic mRNA into structural and accessory proteins
○ Phase 7: Nucleocapsid buds into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) studded with S, E, and M proteins
○ Phase 8: Formation of virion
○ Phase 9: Exocytosis
○ Genetic Material : Positive-sense single-stranded RNA
○ Genome size : 30 kb
○ Contains 5’ cap and 3’ poly A tail
○ Mechanism : Infects respiratory system in humans
○ Entry into cell : Around 10 minutes
○ Eclipse period : Around 10 hours
○ Burst size : Around 1000 virions
○ Diagnosis
○ Type 1: RT-qPCR
○ High accuracy and sensitivity, commonly used as the gold standard
○ Patents have expired, making it affordable
○ Type 2: Droplet digital PCR
○ Type 3: LAMP-based test
○ Single-stranded viral RNA template is looped before PCR
○ Can be performed at room temperature as denaturation step is not required
○ Type 4: NEAR-based test
○ Uses an enzyme similar to restriction enzymes called nicking endonuclease
○ Fastest diagnosis method: Takes less than 15 minutes for ID NOW product
○ Type 5: COVID-19 immunoassay
○ Type 5-1: Antigen test: Attaches antibodies
○ Type 5-2: Antibody detection: Attaches antigens
○ Type 5-3: Neutralization
○ Disadvantage: Cannot distinguish between SARS-CoV-2 and SARS-CoV
○ Type 6: Recombinase polymerase amplification
○ Type 7: CRISPR-based detection
○ CO-RADs (COVID-19 Reporting and Data System)
○ Category 0: Not interpretable due to technical flaws
○ Category 1: Very low likelihood of infection
○ Category 2: Low likelihood, typical infection but not COVID-19
○ Category 3: Equivocal/unsure, could be COVID-19 or not
○ Category 4: High likelihood, suspected COVID-19
○ Category 5: Very high likelihood, typical COVID-19 symptoms
○ Category 6: Proven through RT-PCR
○ Treatment: The only successful treatment is Remdesivir, but it hasn’t contributed to reducing the death rate significantly
○ Arbidol: Inhibits spike and ACE2 interaction and membrane fusion
○ Bamlanivimab + Etesevimab: Binds to S protein’s RBD
○ Camostat Mesylate: Inhibits TMPRSS2
○ Chloroquine: Inhibits membrane fusion
○ EK1C4/HR2P: Inhibits membrane fusion
○ Dexamethasone: Anti-inflammatory response
○ Favipiravir: Inhibits RNA-dependent RNA polymerase
○ Hydroxychloroquine: Inhibits membrane fusion
○ Lopinavir: Inhibits replicase-transcriptase complex 3CLpro
○ Recombinant ACE2: Binds to COVID-19 instead of ACE2
○ Remdesivir: ATP analogue. Inhibits RNA-dependent RNA polymerase
○ Ribavirin: Inhibits RNA-dependent RNA polymerase
○ Ritonavir: Inhibits replicase-transcriptase complex 3CLpro
○ Sarilumab: Specifically binds to IL-6, inhibiting IL-6 signaling
○ Tocilizumab: Specifically binds to IL-6, inhibiting IL-6 signaling
○ Additional Information: Why AIDS treatment works well against coronavirus
○ The nature of RNA viruses
○ Humans create RNA from DNA, and proteins from RNA. Proteins perform essential biological functions.
○ Virus replication involves inserting DNA with viral genetic information into human DNA.
○ Therefore, RNA viruses always require reverse transcriptase enzymes to create DNA from RNA.
○ AIDS virus and coronavirus
○ Both AIDS virus and coronavirus are ssRNA viruses.
○ It is not difficult to infer that coronavirus can be treated due to AIDS therapy.
○ In 2002, South Korea treated SARS virus, a type of coronavirus, with AIDS therapy.
○ Supplement: Coronavirus and herd immunity
○ Official definition of herd immunity: The proportion of infected individuals needed for herd immunity, given the number of hosts n per individual.
○ For coronavirus, with n around 3, approximately 66.6% of the population needs to be infected.
○ Assuming a 1% fatality rate, the conclusion is that 0.67% of the population would die.
● coxsackievirus
○ 7.1 kb, positive-sense ssRNA virus, naked virus
● Ebola virus
○ negative-sense ssRNA virus
● Hepatitis B virus (HBV)
○ dsDNA virus
○ Associated with liver cancer, increased expression of IGF-2 (insulin-like growth factor)
● Hepatitis C virus (HCV)
○ positive-sense ssRNA virus
● Herpes simplex virus (HSV)
○ 154 kb, dsDNA virus, enveloped virus
○ Associated with lymphoma, Kaposi’s sarcoma, inhibits antigen presentation on MHC I of tumor cells
○ Can cause shingles during weakened immune response
○ Highly similar to varicella-zoster virus (VZV)
○ HSC-1: Most common herpes virus
● Human immunodeficiency virus (HIV)
○ positive-sense ssRNA virus
○ Treatment: Reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors), crixsivan (an HIV protease inhibitor used for AIDS therapy)
● Human T-leukemia virus
○ Causes T-cell lymphoma, excessive cytokine secretion in T-cells
● H1-PV
○ 5 kb, ssDNA virus, naked virus
● Influenza virus
○ negative-sense ssRNA virus
○ Comprises multiple types
● NDV
○ 14 kb, negative-sense ssRNA virus, enveloped virus
● MV
○ 16 kb, negative-sense ssRNA virus, enveloped virus
● Parvovirus
○ Characteristics: ssDNA virus, non-enveloped virus
○ Types: Kilham’s rat virus (KRV or RV), Toolan’s H-1, rat parvovirus (RPV, ROPV, rat orphan parvovirus)
● Poliovirus
○ 7.5 kb, positive-sense ssRNA virus, naked virus
● Reovirus
○ 23 kb, dsRNA virus, naked virus
● Rotavirus
○ dsRNA virus
● Simian virus 40 (SV40)
○ Causes monkey lymphoma, inhibits pRb and p53 via T-antigen
● Vaccinia virus (VACV)
○ 190 kb, dsDNA virus, enveloped virus
● Vesicular stomatitis virus (VSV)
○ 11 kb, negative-sense ssRNA virus, enveloped virus
● Varicella-zoster virus (VZV)
○ Infects 90% of the world’s population, highly contagious
○ Causes chickenpox and shingles
○ Childhood infection leads to chickenpox
○ Persists symptomlessly around nerve ganglia, reactivating as shingles when immunity drops
○ Highly similar to herpes virus
2. Bacteria
● Acetobacter
○ Forms biofilms, facultative anaerobes
● Agrobacterium tumefaciens
○ Carries Ti plasmid
○ Induces tumors called crown gall in plants
● Azotobacter
○ Fixes nitrogen in soil
● Bacillus anthracis
○ Gram-positive
● Bacillus subtilis
○ Gram-positive
● Chlamydophila pneumoniae
○ Causes pneumonia
○ Intracellular pathogen
● Corynebacterium diphtheriae
○ Secretes diphtheria toxin
● Escherichia coli (E. coli)
○ Gram-negative
○ Commensal organism
○ 61 E. coli genomes share 20 genes (Lukjancenko et al. 2010)
○ Type 1: E. coli DH5α
○ Bacteria belonging to risk group 1
○ Derived from K-12 strain, considered safe
○ Genotype: fhuA2 alc(del)U169 phoA glnV44 φ80’ lacZ(del)M15 gyrA96 recA1 relA1 endA1 thi-1 hsdR17
○ Used in gene cloning
● Haemophilus influenzae
○ Causes pneumonia
● Helicobacter pylori
○ Gram-negative
● Legionella pneumophila
○ Causes pneumonia
○ Intracellular pathogen
● Listeria monocytogenes
○ Gram-positive
○ Possesses several flagella, intracellular pathogen
○ Pathogenic to animals and birds
○ Produces pore-forming hemolysin LLO (listeriolysin) known as LLO (listeriolysin)
○ Causes listeriosis
○ Infections by Listeria monocytogenes in humans or animals
○ Mostly septicemia, meningitis, encephalitis
○ Named “monocytogenes” due to increased monocytes upon infection
● Mycobacterium tuberculosis (MTB)
○ Gram-positive
○ Has thin peptidoglycan layer and extensive lipid layer, causing difficulty in staining
● Mycoplasma pneumoniae
○ Lack cell walls
○ Causes pneumonia
● Pseudomonas aeruginosa
○ Produces single-chain exotoxin A with three domains
○ Domain II promotes endosomal escape
● Salmonella enteritidis
○ Causes intestinal infections
● Salmonella typhimurium
○ Among enteric flagellated rods
○ Sensitive to mutagens, commonly used in Ames test
○ Commonly used strains in Ames test
○ Salmonella typhimurium TA98
○ Salmonella typhimurium TA100
○ Salmonella typhimurium TA1535
○ Salmonella typhimurium TA1537
○ Escherichia coli WP2 uvrA (pKM101)
○ Siderophore synthesis
○ Siderophores bind to iron
○ Reaction rate decreases above 37°C
○ Reaction stops at 40.3°C
● Staphylococcus aureus
○ Gram-positive
○ Causes pneumonia
● Streptococcus pneumoniae
○ Gram-positive
○ Cocci-like distribution
○ Causes pneumonia
● Vibrio cholerae
○ Activates CFTR receptor in intestinal epithelial cells, leading to massive Cl- secretion
○ Causes massive water loss through diarrhea (cholera)
○ Cholera toxin’s subunit B is involved in attaching to intestinal epithelium
○ Cholera pandemics primarily caused by O1 serotype
○ Typically spreads through water contaminated by cholera patient’s excretions
○ Gram-negative bacteria with flagella
3. Archaea
● Methanogens
○ Generate methane in energy metabolism
○ Some inhabit the intestines of herbivores like cows
● Thermus aquaticus
○ Thrives in high-temperature hot springs
○ First discovered in the 1960s in Yellowstone National Park
○ Synthesizes Taq polymerase
4. Fungi
● Blastomycosis
○ Distributed in the eastern United States
○ Causes pneumonia
● Coccidioidomycosis
○ Distributed in California and the southwestern United States
○ Causes pneumonia
● Cryptococcus
○ Distributed throughout the United States
○ Causes pneumonia
● Histoplasmosis
○ Distributed in the Ohio and Mississippi River valleys
○ Causes pneumonia
● Pneumocystis jiroveci
○ Causes pneumonia
○ Especially concerning for immunocompromised individuals
● Saccharomyces
○ Yeast that produces the most alcohol during grape juice fermentation
○ Used in wine production
5. Protists
● Naegleria fowleri
○ Inhabit lakes and rivers
○ Can enter the human body and cause meningitis
● Nannochloropsis oculata
○ Accumulates lipids during nitrogen deficiency
● Paramecium caudatum
○ Moves using cilia, exhibits forward and backward motion
● Plasmodium vivax
○ Causes malaria
○ Complex life cycle involving human and mosquito hosts, sexual and asexual reproduction
Figure 2. Life cycle of malaria
○ Possesses 2 sets of 28 chromosomes
Input : 2019.03.17 11:51