BACTERIOPHAGES

     Bacteriophage, normally called phage, is viruses that infect prokaryote. They are obligate intracellular parasites that are capable of existence as phage particles outside the host cell but can only reproduce inside the cell.

    They consist of a nucleic acid genome surrounded by a protein coat called a capsid.

     Phages possess the ability to infect a prokaryote and redirect the cell to synthesize phage components.

STRUCTURE OF BACTERIOPHAGE:

    • Phage, like viruses, have number of shapes

    • The genome can be DNA or RNA, single stranded or double stranded, circular or linear.

    • Some phage are very small such as E.coli, single-stranded RNA phage, MS2, whose genome contain information for only for proteins, while others are large likeT4 whose genome encodes around 135 different proteins.

PHAGE LIFE CYCLE:

            • A life cycle of phage starts by the adsorption of the phage onto the specific receptor on the bacterial cell surface followed by the penetration of the genetic material into the host.

            • Enzymes encoded by the phage genome are synthesized, which is followed by nucleic acid replication.

      • Finally, phage capsid proteins are made and assembled into a new phage coat, at the same time packaging a copy of the genome.

      • The phage are released, normally by lysis, into the surrounding medium.

LYSOGENIC LIFE CYCLE:

              • Some phage, a typical example being phage λ, instead of starting the lytic cycle on entry into the cell, produce repressor protein that stop the phage replication.

       • The phage enters a state call lysogeny in which genome is replicated at the same time as the host chromosome and is passed from one generation to the next.

       • the phage may be induced from this lysogenic state spontaneously and enter into the lytic cycle.

       • In order to replicate with the host, most lysogeny phage integrate into the chromosome to form a prophage but some like, P1, exist in the cytoplasm in a form similar to plasmids.

   

How Pharmacokinetics works in Pharmaceutical industry?

1. Pharmacokinetics refers to how the body absorbs, distributes, metabolizes, and eliminates drugs. It involves studying how drugs move through the body, how they are processed, and how their concentration changes over time. This information helps in determining the appropriate dosage and dosing intervals for medications.

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3. Pharmacokinetics plays a crucial role in the pharmaceutical industry in several ways:

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5. Drug Development: Pharmacokinetic studies help pharmaceutical companies understand how a drug is absorbed, distributed, metabolized, and excreted in the body. This information aids in designing effective and safe dosing regimens for new drugs.

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7. Dosing Regimen: Pharmacokinetics helps determine the optimal dosage and dosing frequency for a drug. This ensures that the drug achieves therapeutic levels in the body while avoiding toxic concentrations.

8. Bioavailability: Pharmacokinetic studies assess the bioavailability of a drug, which is the fraction of the administered dose that reaches the systemic circulation. This information helps in comparing different formulations of the same drug or different drugs with similar effects.

9. Drug Interactions: Understanding the pharmacokinetics of multiple drugs can reveal potential interactions. This is important to avoid harmful effects or reduced efficacy when multiple drugs are taken together.

10. Special Populations: Pharmacokinetic studies provide insights into how drugs behave in different populations, such as children, the elderly, pregnant women, and patients with specific medical conditions. This helps tailor dosing for these groups.

11. Generic Drug Equivalency: For generic drugs, pharmacokinetic studies demonstrate that the generic version behaves similarly to the brand-name drug in terms of absorption, distribution, and elimination.

12. Therapeutic Drug Monitoring (TDM): In some cases, therapeutic drug monitoring involves measuring drug concentrations in the blood to ensure they are within the therapeutic range. Pharmacokinetics helps determine the appropriate timing for these measurements.

13. Drug Safety: Understanding how a drug is metabolized and eliminated helps identify potential safety concerns, such as the risk of accumulation in specific organs or tissues.

14. Formulation Development: Pharmacokinetics can guide the formulation of drugs, helping manufacturers choose appropriate delivery methods (e.g., tablets, injections, patches) to achieve desired drug concentrations.

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    Formulation of drug

    
    

    
    

16. Regulatory Approval: Pharmacokinetic data are submitted to regulatory agencies to demonstrate the safety and effectiveness of new drugs, supporting their approval for market distribution.

In summary, pharmacokinetics is a fundamental tool that helps pharmaceutical companies develop safe and effective drugs, determine appropriate dosing, and navigate regulatory requirements.

ASSIMILATION OF SULPHUR

ASSIMILATION OF SULPHUR : 

Sulphates taken up by the roots are the major sulfur source for growth, though it has to be reduced to sulphide before it is further metabolized. Root plastids contain all sulphates reduction enzymes, but the reduction of sulfate to sulphide and its subsequent incorporation into cysteine predominantly takes place in the shoot, in the chloroplast.

Sulphates  is taken up by the roots that have high affinity. The formation of cysteine is the direct coupling step between sulfur and nitrogen assimilation in plants. This differs from the process in yeast, where sulfide must be incorporated first in homocysteine then converted in two steps to cysteine

All photosynthetic organisms, sulfate reduction occurs in the plastids, with the notable exception of Euglena gracilis, which locates the sulfate-reducing enzymes in mitochondria . Whereas the reductive steps are localized exclusively in the organelles, ATP sulfurylase is also present in the cytosol. Accordingly, plants and algae possess multiple isoforms of ATP sulfurylase . Very surprisingly, plant ATP sulfurylases have a different evolutionary origin than those from green algae, and they are more similar to their animal counterparts . 

Sulfate uptake and assimilation are tightly regulated according to the plant demands for reduced sulfur. Among other compounds affecting sulfate assimilation, the phytohormones play the most prominent roles. 

YEAST

Yeast

Classification:

Domain        -  Eukaryota
Kingdom      - Fungi
Phylum         - Ascomycota
Subphylum  - Saccharomycotina
Class            - Saccharomycetes
Order            - Saccharomycetales
Family          - Saccharomycetaceae
Genus           - Saccharomyces
Species        - S. cerevisiae (Brewer's/Baker's yeast)

Definition of yeast:

• A yeast is a unicellular fungus which consists of a single nucleus.
• There are about 1500 species most of which are in the phylum Ascomycota and a few being in phylum Basidiomycota
• It can reproduce sexually through spore formation or asexually by budding and transverse division.
• The shape of the yeast is spherical to egg-shaped.
• Yeast cells are larger than bacteria.
• Flagella and cilia are non-existent in yeast.
• Yeast grow as smooth colonies on agar plates much like bacteria.

Saccharomyces cerevisiae:

• S. cerevisiae is a commonly used yeast.
• It is ovum cell shaped.
• It's diameter varies between 5-10 micrometers.
• This yeast can be cultivated easily and quickly.
• It can multiply within 1.5 -2 hours at 30°C.
• The maintenance is cheap and efficient.
• It is used in beer, bread and fermented wine industries. 

Reproduction of Saccharomyces cerevisiae:

S. cerevisiae reproduces at haploid and diploid states.

      As long as nutrients remain plentiful, haploid and diploid cells undergo mitosis to produce haploid and diploid daughter cells, respectively. Each daughter cell leaves a scar on the mother cell as it separates and the daughter cells bud only from unscarred regions of the cell wall. When a mother cell has no more unscarred cell wall remaining, it will no longer be able to reproduce and will die (senesce).

     When nutrients are limited, diploid S. cerevisiae cells undergo meiosis to produce four haploid that remain bound within a common cell wall called the ascus. Upon, the addition of nutrients, two haploid cells of opposite mating types come into contact and fuse to create a diploid. Generally, only cells of opposite mating types can fuse and this process is tightly regulated by the action of pheromones.

Advantages:

1. Yeast grows rapidly, is a common host species and can be easily handled in the laboratory.
2. Its a healthy mix of bacteria in your gut.
3. It can fight pathogens and help to absorb the vitamins and minerals.
4. It supports the nervous system and enhances immunity.
5. It promotes hair, skin and nail health.
6. It keeps your digestive system healthy and working.
7. Yeast extract is an aqueous extract of brewer's yeast
8. Yeast extract is a good source of B vitamins, nitrogen and carbon. 

Diseases :

Candidiasis

According to the CDC, Candidiasis is a yeast infection caused by Candida (a type of yeast). Some species of Candida like Candida albicans can cause infection in people. Candida normally lives inside the body (in places such as the mouth, throat, gut, and vagina) and on skin without causing any problems. 

Sometimes Candida can multiply and cause an infection if the environment inside the vagina changes in a way that encourages its growth. Candidiasis in the vagina is commonly called a “vaginal yeast infection.” Other names for this infection are “vaginal candidiasis,” “vulvovaginal candidiasis,” or “candidal vaginitis.” 

Sometimes, Candida can multiply and cause an infection if the environment inside the mouth, throat, or esophagus changes in a way that encourages fungal growth.

Candidiasis in the mouth and throat is also called thrush or oropharyngeal candidiasis. Candidiasis in the esophagus (the tube that connects the throat to the stomach) is called esophageal candidiasis or Candida esophagitis. Esophageal candidiasis is one of the most common infections in people living with HIV/AIDS.

Antifungal medicines get rid of yeast infections in most people. If you have a weak immune system, treatment might be more difficult.

ASSIMILATION OF PHOSPHORUS

 ASSIMILATION OF PHOSPHORUS 

                    Phosphorus is obtained from inorganic or organic phosphate. They are the component of  nucleic acids (DNA & RNA), phospholipids, ATP, coenzymes like NADP , bone and teeth .

They plays an vital role in the regulation gene transcription, activation of enzymes,maintenance of normal ph in the extracellular fluids, and intracellular energy fluids .Inorganic phosphate is incorporated through the formation of ATP in one of the three ways by (1) photophosphorylation , (2) oxidative phosphorylation , and (3) substrate-level phosphorylation. Glycolysis provides an example of the third process . phosphate is joined with glyceraldehyde 3-phosphate to give 1,3-bisphosphoglycerate , which is further used in ATP synthesis .

      Glyceraldehyde 3-P + Pi +NAD+   --------> 1,3 - biposphoglceratte + NADH + H+

       1,3-bisphosphoglycerate + ADP ---------->3-phosphoglycerate + ATP

 

Inorganic phosphorus is found abundant in the rocks . Through weathering and rain breaks the phosphorus in rocks and it travels in the soil and water . When plants and animals consume phosphorus from soil and freshwater it moves into their cell where inorganic phosphorus is converted into organic phosphorus .When an organisms die or excrete the wastes the bacteria converts organic into inorganic phosphate .

PHOTOSYNTHETIC CO2 FIXATION

PHOTOSYNTHETIC OF CO2 FIXATION:

INTRODUCTION :

CO2 is the  principal carbon source of Autotrophs, and the reduction and incorporation of CO2 requires much energy.

 Photoautotrophs obtain energy by trapping light during the light reactions of photosynthesis, and chemolithoautotrophs derive energy from the oxidation of inorganic electron donors. 

Autotrophic CO2 fixation is crucial to life on Earth because it provides the organic matter on which heterotrophs depend. 

Six different CO2-fixation pathways have been identified in microorganisms.

 Eukaryotic autotrophs and most aerobic bacterial autotrophs use the Calvin-Benson cycle, also called the Calvin cycle. Other pathways are used by some obligatory anaerobic and microaerophilic bacteria and archaea. 

CALVIN-BENSON CYCLE:

OVERVIEW:

• The Calvin cycle refers to the light-independent reactions in photosynthesis that take place in three key steps.

• Although the Calvin Cycle is not directly dependent on light, it is indirectly dependent on light since the necessary energy carriers (ATP and NADPH) are products of light-dependent reactions.

• In fixation, the first stage of the Calvin cycle, light-independent reactions are initiated; CO2 is fixed from an inorganic to an organic molecule.

• In the second stage, ATP and NADPH are used to reduce 3-PGA into G3P; then ATP and NADPH are converted to ADP and NADP+, respectively.

• In the last stage of the Calvin Cycle, RuBP is regenerated, which enables the system to prepare for more CO2 to be fixed.

IN DETAIL:

The Calvin-Benson cycle is also called the reductive pentose phosphate cycle because it is essentially the reverse of the pentose phosphate pathway. 

The reactions of the Calvin-Benson cycle occur in the chloroplast stroma of eukaryotic autotrophs. In cyanobacteria, the cycle is associated with inclusions called carboxysomes. These polyhedral structures contain the enzyme critical to the Calvin-Benson cycle and are the site of CO2 fixation.

The Calvin-Benson cycle is divided into three phases: carboxylation phase, reduction phase, and regeneration phase .

During the carboxylation phase,the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO)catalyzes the addition of CO2 to the 5-carbon molecule ribulose 1,5-bisphosphate (RuBP), forming a 6-carbon intermediate that rap- idly and spontaneously splits into two moles phosphoglycerate glycerate (PGA). PGA is an intermediate of the Embden-Meyerhof pathway (EMP). 

In the reduction phase of the Calvin-Benson cycle, PGA is reduced to glyceraldehyde 3-phosphate by two reactions that reverse two EMP reactions. The EMP reactions differ from the Calvin-Benson cycle reactions in that the Calvin cycle enzyme glyceraldehyde 3-phosphate dehydrogenase uses NADPH rather than NADH .

 Finally, in the regeneration phase, RuBP is reformed, so that the cycle can repeat. In addition, this phase produces carbohydrates such as fructose 6-phosphate and glucose 6-phosphate, which are precursor metabolites .This portion of the cycle is similar to the pentose phosphate pathway and involves transketolase and transaldolase reactions.  

To synthesize fructose 6-phosphate or glucose 6-phosphate from CO2, the cycle must operate six times to yield the desired hexose and reform the six RuBP molecules.

6RuBP + 6CO2 → 12PGA → 6 RuBP + fructose-6-p

The incorporation of one CO2 into organic material requires three ATP and two NADPH. The formation of glucose from CO2 may be summarized by the following equation.

6CO2 + 18 ATP + 12 NADPH + 12H+ + 12H2O → glucose + 18 ADP + 18 Pi + 12 NADP+

                                            The Calvin Benson cycle

 

OTHER CO2 FIXATION PATHWAYS:

TCA CYCLE:

The first alternative CO2-fixation pathway discovered was the reductive TCA cycle, which is used by some autotrophs in the bacterial phyla Aquificae, Proteobacteria, Nitrospirae, and Chlorobi. The reductive TCA cycle is so named because it runs in the reverse direction of the normal, oxidative TCA cycle. 

The Reductive TCA Cycle

OTHERS:

The remaining CO2-fixation pathways are used by members of the bacterial phylum Chloroflexi (3-hydroxypropionate bicycle): The reductive acetyl-CoA pathway  is used by some methanogens; the

3-hydroxypropionate/4-hydroxybutyrate pathway is used by members of the order Sulfolobales; and the dicarboxylate/ 4-hydroxybutyrate cycle was discovered in members of orders Thermoproteales and Desulfurococcales. A seventh pathway has been proposed that links CO2 fixation to dissimilatory phosphite oxidation. This proposal is supported by genomic evidence, but has not yet been established biochemically.

ACTINOMYCETES

ACTINOMYCETES

(Actino means - Ray; Mycetes means - Fungi),  Coined By  :  Harz in 1877

DEFINITION:

               Actinomycetes are unicellular, aerobic and gram-positive bacteria that forms branching hyphae . They normally undergo fragmentation and produce asexual spores. They closely resemble fungi in overall morphology. Most of the actinomycetes are non-motile when motility is present is confined to flagellated spores. 

 

  GENERAL CHARACTERISTICS:

              * Actinomycetes species are  primarily soil inhabitant and widely distributed . Additional they are also a marine habitat . Therefore they are also known as a "Treasure house of the secondary metabolites .

              *  Actinomycetes form colonies that are leathery and many produce pigments and are responsible for the geosmin ( earthy) odor . 

              * The second edition of Bergey's Manual classifies  the actinomycetes and other high G + C gram positive bacteria using 16SrRNA data . 

EXAMPLES OF ACTINOMYCETES: 

     Nocardia 

                 Micromonospora

            Streptomyces

                              Corynebacterium spp

                    Streptomyces spp

    Frankia 

                    Geodermatophilus 

                                              

ADVANTAGES:

             * They play an vital role in degrading an enormous number and variety of organic compounds and are extremely important in the mineralization of organic matter .

             * The aerobic gram-positive actinomycetes belonging to the genus Frankia are bacteria that grows in symbiotic association with the roots of higher non leguminous plants and   fixes atmospheric nitrogen .   

              * They are producers of the most of the antibiotics such as amphotericin, nystatin, chloramphenicol, gentamycin, erythromycin, vancomycin, tetracycline, novobiocin, neomycin, etc.

             * Actinomycetes plays an extremely important in the treatment of cancer, as well as variety of applications in bioremediation .

DISADVANTAGES: 

            * Actinomyces are responsible for actinomycoses, ocular infections, and periodontal disease  in human. The most important pathogen is A.israelii

            *  C.diphtheria is the causative agent of diphtheria in human

            * N.asteriodes is a species of nocardia that cause nocardiosis ,a severe pulmonary infection in human and other animals .

LIFE CYCLE OF ACTINOMYCETES: