The Corona Chapter of Human Life; What We Need to Know about Epidemics and Pandemics

Epidemics and Pandemics
In 1918 and 1919, a very dangerous and deadly Type A Influenza spread throughout the world. Most of the victims were young and healthy adults. In the past, it was believed that 50 million people were killed during this pandemic, but recent studies show that about 100 million people were killed by the disease, which is equivalent to five percent of the world’s population that year. One of the pandemics that started in the 80s and continues to this day is AIDS. There are currently about 38 million people living with AIDS worldwide. About 25 million people have died from the disease so far, and just in 2018, about 770,000 people died from the disease.
The Filoviridae family of viruses includes several deadly and dangerous viruses that cause hemorrhagic fever. Ebola and Marburg viruses are members of this virus family that have caused several epidemics in African countries.
The Coronaviridae virus family includes viruses that commonly cause dangerous respiratory infections. For example, Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as well as Coronavirus disease 2019 (COVID-19) are members of this family that have caused pandemics and epidemics over the years.

Genetics of Viruses
The genetics of human and animal viruses are not yet fully understood. The main reason for this is the lack of cell structure and their specific metabolism. Because their proliferation is completely dependent on and tied to the host cell, it is difficult to examine in detail and its various stages are difficult to follow. On the other hand, viruses are genetically more stable than bacteria, and genetic changes in them are very rare in other human and animal viruses, except for influenza and AIDS viruses, and it is very difficult to obtain new mutants or recombinants. Therefore, their genetic study is not easily possible and its difficulty is reflected in treating viral diseases.

Bilateral Genetic Changes in Viruses
Bilateral changes in the genome of viruses occur when the genome of two active viruses enters a cell at the same time and infects it, and the host cell replicates them both. In such cases, there is a high probability of bilateral genetic mutations between the two viruses, in which part of the nucleic acid of the first virus joins the nucleic acid of the other virus, bringing new genes to the original genes. If part of the nucleic acid of the first virus joins the nucleic acid of the second virus and part of the nucleic acid of the second virus joins the nucleic acid of the first virus, then the genome of each of them loses a part and gains another part.

In general, the following possibilities can be observed in such cases:
Recombination
Recombination is the reciprocal restorative exchange of parts of the genome of two active viruses that have simultaneously entered a cell and infected it. Accidental exchange of part of the genome of two active viruses sometimes increases and decreases virulence, and changes in virus antigens may occur. It results in acquiring new features when the virus has previously lackd it and changes compeltly by acquiring it. Recombination has been reported in smallpox, influenza, and polio viruses, and bacteriophages.

Cross-Activation
The confluence of an active virus genome with an inactive virus genome, which have simultaneously entered the cell and infected it, sometimes leads to cross-exchange of a part of their genome, and both viruses acquire new properties as a result of these changes, resulting in both viruses emerging and activing. For example, to prepare a vaccine against viruses that cannot replicate in certain cells, they can be activated by genetic changes to replicate them in those cells.

Incremental Reactivation
It is when two inactive viruses enter a cell and their inactive nucleic acids repair each other, resulting in an active virus with characteristics of both. This, and the reciprocal genetic enhancement that occurs in this case, raises the possibility of an active and violent virus.

Bilateral Non-Genetic Changes
When two viruses enter a cell at the same time and are reproduced, phenotypic mixing occurs if the genetic information of the first virus (genotype) is replaced in the capsid (phenotype) of the second virus. This gives rise to two new viruses whose phenotype and genotype have been changed by chance. This condition is not stable, if each infects a cell, the newly formed viruses lose the borrowed phenotype and reveal their original phenotype.

Genotype Mixing
Sometimes a cell infection with two different viruses leads to mixing of their genotypes; Therefore, if a virus contains genetically complete information of two different viruses, that is, two different genomes are in its capsid, we are talking about genotype mixing. In such cases, there is also no genetic stability. The result of the first multiplication of that virus will lead to the emergence of two different viruses. This phenomenon has been reported in paramyxoviridae.

Interference
Experience has shown that sometimes cell cultures show a kind of immunity to infection with other viruses after being infected with a virus. Even if another virus penetrates the cell, it does not multiply. This is most likely due to the secretion of cellular interferon or the control and conduction of cell metabolism by the infectious virus and the inability to control and direct the cell by the second virus. The reverse-interference is also possible. In this case, the cells infected with the first virus intensify and increase the proliferation of the second virus. This is probably because the genetic information in the second virus prevents the release of interferon. The reverse-interference is another possibility that by working together with two viruses in preventing the continuation of cell metabolism, the result is in favor of both viruses and makes possible the multiplication stages of both viruses. Sometimes when two defective viruses infect a cell, although neither is possible on its own and is unlikely to multiply, the genetic information of the two viruses can complement each other and multiply by inhibiting and controlling the cell metabolism of both.

Mycobacterium
Mycobacterium is a genus of the Enterobacteriaceae family. The Mycobacterium genus includes important pathogens such as Mycobacterium tuberculosis and Mycobacterium leprae. The Greek prefix “myco” means fungus because the bacterium grows like a fungus on the surface of a liquid culture medium.

Microbiological Features
Mycobacterium are aerobic, immobile bacteria (other than Mycobacterium marinum, which is motile within Macrophages) and aid-fast. They do not produce capsules or endospores. However, a new article in the scientific journal PNAS shows spore production in Mycobacterium marinum and possibly Mycobacterium bovis; But other scientists have challenged and opposed the argument. Mycobacteria are acid-fast bacteria. They have a thick cell wall. The cell wall in Mycobacterium is hydrophobic, waxy, and rich in mycolic acids. The cell wall contains a layer of mycolate and a layer of peptidoglycan, which are joined together by a special type of polysaccharide called Arabinogalactan. The cell wall causes the bacteria to become stubborn and resistant to environmental conditions. Biosynthetic pathways of cell wall components are good targets for new TB drugs. Many species of Mycobacterium grow on simple culture media (containing amino acids and ammonium as a source of nitrogen, glycerol as a source of carbon, and mineral salts). Suitable growth temperatures for different species vary from 20 to more than 50 ° C depending on the species. Some species are very difficult to cultivate (difficult species) and others have very long division times, such as Mycobacterium leprae, which takes 20 days each time to divide. Just compare this time with E.coli split time every 20 minutes! Also, genetic manipulation methods in Mycobacteria are not as advanced as other bacteria. Mycobacteria can be classified according to their growth rate. Those that produce visible colonies with the naked eye within 7 days are called fast-growing, and others are called slow-growing.

Pathogenesis
Mycobacteria can infect the host without any symptoms. For example, millions of people worldwide have asymptomatic Mycobacterium tuberculosis infection.
Tuberculosis infection (or infection with the TB germ) occurs when a person carries the TB bacillus in their body, but the number of bacteria is low and they are dormant. In this case, these dormant bacteria are under the control of the immune system and do not cause disease.
Mycobacterium infections are difficult to treat. The hard wall of bacteria is the cause of this. They are also naturally resistant to some antibodies to cell wall biosynthesis, such as penicillin. Their special cell wall makes them stable for a long time against acids, bases, detergents, antibiotics, immune system and so on. Most mycobacteria are sensitive to the antibiotics Clarithromycin and Rifamycin. The surface and secretory proteins of Mycobacteria, like other bacteria, are involved in their pathogenesis.

Medical Classification
Mycobacteria are divided into several groups according to medical criteria: Mycobacterium tuberculosis complex, which includes Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, and Mycobacterium leprae; And Nontuberculous mycobacteria, or NTMs, which can cause lung diseases such as tuberculosis, lymphadenitis, or skin infections.

Genome
Comparative sequencing of Mycobacteria shows unique proteins in different species of Mycobacteria. Also, 14 proteins have been found only in Mycobacterium and Nocardia species, which indicates a close relationship between the latter two genera.

Mycobacteriophages
There are phages (viruses) that infect mycobacteria. They may be used in the future to treat tuberculosis (phage therapy).

Species
Different species of Mycobacterium can be distinguished using phenotypic tests. In the old classification, appearance characteristics and growth rate were used to classify mycobacteria. The new classification uses the science of classification and phylogenetics for classification. Here are some important species:

Slow-GrowingMycobacterium tuberculosis complex
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium africanum
Mycobacterium microti
Mycobacterium avium complex
Mycobacterium avium subsp. avium
Mycobacterium avium subsp. Paratuberculosis
Mycobacterium avium subsp. Silvaticum
Mycobacterium avium subsp. Hominissuis
Mycobacterium colombiense
Mycobacterium indicus pranii
Mycobacterium gordonae clade
Mycobacterium gordonae
Mycobacterium asiaticum
Mycobacterium kansasii clade
Mycobacterium kansasii
Mycobacterium gastri
Mycobacterium nonchromogenicum clade
Mycobacterium nonchromogenicum
Mycobacterium terrae
Mycolactone-Producing Mycobacterium
Mycobacterium ulcerans
Mycobacterium pseudoshottsii
Mycobacterium simiae clade
Mycobacterium simiae
Mycobacterium genavense

Unclassifiable Species
Mycobacterium leprae
Mycobacterium lepraemurium
Mycobacterium lepromatosis
Mycobacterium marinum
Mycobacterium szulgai
Mycobacterium scrofulaceum
Mycobacterium xenopi

Moderate-Growing Species
Mycobacterium intermedium

Fast-Growing Species
Mycobacterium chelonae clade
Mycobacterium chelonae
Mycobacterium abscessus
Mycobacterium fortuitum clade
Mycobacterium fortuitum
Mycobacterium parafortuitum clade
Mycobacterium parafortuitum
Mycobacterium vaccae clade
Mycobacterium vaccae
Unclassifiable Species:
Mycobacterium flavescens
Mycobacterium phlei
Mycobacterium smegmatis

Spores
Spores are resistant structures in three groups of bacteria: Bacillus, Clostridium, and Sporosarcina. Only these three groups have the ability to produce spores, and spore production is an integral part of the life of these bacteria. Usually, these bacteria tend to produce spores in unfavorable environmental conditions, which make them resistant to unfavorable physical and chemical factors of the environment (heat of 100 degrees, pasteurization heat, heat of tendonization, etc.). In the sporolution phase, an energy source called Polyhydroxybutyrate is used.

Chemical Nature of Spores
4 layers surround the spores, which include from outside to inside:
The outermost layer is exosporium, the second layer is coat spore, the third layer is cortex and the central layer is core. The core contains peptidoglycan and the cytoplasmic membrane, and at the center of the core are the cytoplasm, DNA, and RNA.
Most of the spores are made of calcium and dipicolinic acid, and the presence of these two strengthens the spores. Manganese ions and the amino acid cysteine are also abundant. Cysteine makes spores resistant to X and UV rays. Water, phosphorus and phosphate are also found in very small amounts in the chemical structure of spores. Spore-bearing bacteria are highly regarded in food microbiology, especially in the canning industry. These bacteria cause food poisoning and sometimes produce toxins that cause symptoms such as nausea, diarrhea and vomiting.

Spore-Bearing Bacteria
Bacillus anthracis, central spores
Clostridium tetani, subterminal spores
Clostridium botulinum, subterminal spores
Gas gangrene, subterminal spores