MICROBIOLOGY

ANTIVIRAL AGENTS:                                                     Viruses are acellular, intracellular obligatory parasites so the chemotherapeutic agents must enter the host's cell to attack the viruses. Besides, virus don't have complex structure or cell wall & membrane & they are only involved in few physiological activity other than replication. Therefore,there are limited antiviral agents & must antiviral agents interrupt the viral replication.  Amantadine & Zanamivir( prevents attachment of Influenza virus to host cell membrane). Acyclovir & Ganciclovir ( They are incorporated into viral DNA during replication cycle of HSV & CMV). Anti-HIV drugs like Nevirapine( they binds & inhibits reverse transcriptase)  Interferons: They are small glycoproteins cells exposed to interferon develop antiviral properties. ie interference of protein synthesis .  Cited by Kamal Singh Khadka Msc Microbiology, TU                       

ANTIFUNGAL DRUGS:                       3) Amphotericin B:   It is a polyene antifungal drugs often used intravenously for systemic fungal infections. It was originally extracted from Streptomyces nodosus,  a filamentous bacterium. Oral preparations of  amphotericin b is used to treat thrush, these are virtually nontoxic in contrast to typical intravenous therapy doses. It is also commonly used in tissue culture to prevent fungi from contaminating cell cultures. It is antiprotozoal drug also( used to treat parasitic protozoan  infections such as visceral leishmaniasis & primary amoebic meningoencephalitis). Mechanism of Action: As with other polyene antifungals, amphotericin b binds with ergosterol , a component of fungal cell membranes, forming  transmembrane channel that leads to  monovalent ions(Potassium,  hydrogen, chloride, sodium ions) leakage, which is  primary effect for fungal death. The actual mechanism may be complexed & multifaceted. Please visit these

ANTIFUNGAL DRUGS: 2) Griseofulvin :  It is an antifungal drug that is administered orally.  It is used both in animals & in humans, to treat fungal infection of skin & nails . It is produced  by the culture of some strains of Penicillium griseofulvum.  Mechanism: The drugs binds to tubulin ,interfering microtubule function, thus inhibiting mitosis.  It binds to keratin in keratin precursor cells & makes them resistant to fungal infections. It is only when hair or skin is replaced by keratin griseofulvin complex that the drug reaches its site of action. Griseofulvin will then enter the dermatophyte through energy dependent transport processes & bind to fungal microtubules. This alters the processing for mitosis & also underlying information for deposition of fungal cell walls. Please visit these links: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682295.html http://www.mayoclinic.com/health/drug-information/DR600735 http://www.drugs.com/mtm/griseof

ANTIFUNGAL DRUGS :      There are few drugs available for the treatment of fungal diseases. Some of them are; 1) Nystatin :   It  is a polyene antifungal drug used for infection of intestine,vagina, or oral cavity. It is produced by Streptomyces noursei. It is also used for treatment of infection caused by Candida albicians . It alters permeability of cell membrane by combining with fungal sterols.  Please visit these links: http://en.wikipedia.org/wiki/Nystatin http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682758.html http://www.rxlist.com/nystatin-oral-suspension-drug.htm http://www.webmd.com/drugs/mono-8052-NYSTATIN+TABLET+-+ORAL.aspx?drugid=8893&drugname=nystatin+Oral                                  Fig: structure of nystatin                                          Fig: Oral Nystatin USP                                               Fig:Nystatin cream 

4)   INHIBITION OF SPECIFIC ENZYME SYSTEM:       Sulfonamides are synthetic antimicrobial agents that contains sulfonamides group. It targets bacterial metabolic pathways. In bacteria, sulfonamides acts as competitive inhibitor of the enzyme dihydropteroate synthetase(DHPS),an enzyme responsible for folate synthesis. Due to this microorganisms get starved of folate & dies. To know please visit these links: http://en.wikipedia.org/wiki/Sulfonamide_(medicine) http://en.wikipedia.org/wiki/Enzyme_inhibitor http://www.chemeddl.org/alfresco/service/org/chemeddl/ttoc/ttoc_results/?id=22037&num_results=3&guest=true http://www.elmhurst.edu/~chm/vchembook/651enzymeinhibit.html http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Antibiotics/Antibiotics.HTML http://www.elmhurst.edu/~chm/vchembook/653sulfa.html Fig: Enzyme Inhibitors Fig: Mutant HIV protease Enzyme

INHIBITION OF NUCLEIC ACID & PROTEIN SYNTHESIS: 4) Erythromycin :   It is macrolide antibiotic that has an antimicrobial similar spectrum to or slighter wider than penicillin  & often prescribed to those  who have allergy of penicillins.  It is produced by  Streptomyces erythraeus.   It is active against Gram positive, some Gram negative, & pathogenic spirochaetes.  Its mode of action is similar to chloramphenicol . To know more please visit these links: http://en.wikipedia.org/wiki/Erythromycin http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682381.html http://www.webmd.com/drugs/drug-3959-Erythromycin+Oral.aspx?drugid=3959&drugname=Erythromycin+Oral

INHIBITION OF NUCLEIC ACID & PROTEIN SYNTHESIS: 3). Chloramphenicol : Chloramphenicol is considered as pro typical broad spectrum antibiotics alongside tetracycline & is effective against a  wide variety of Gram positive & Gram negative bacteria, most anaerobic microorganisms. Mechanism of Action:                      Chloramphenicol  is a bacteriostatic antibiotic that stops bacterial growth by inhibiting protein synthesis. It prevents protein chain elongation by inhibiting the peptidyl transferase activity of bacterial ribosome. It specifically binds  to A2451& A2452 residues in the 23S r RNA of 50S ribosomal unit, preventing polypeptide formation. It directly interferes substrate binding . To know more please donot bother to visit the following links: http://en.wikipedia.org/wiki/Chloramphenicol http://www.patient.co.uk/medicine/Chloramphenicol-eye-preparations.htm  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC357302/ http://www.drugbank.ca/drugs/DB00446

3)  INHIBITION OF NUCLEIC ACIDS & PROTEIN SYNTHESIS:   2. Tetracycline :  Tetracycline is a broad spectrum antibiotics produced by a mutant strain of Streptomyces  auerofaciens .  It inhibits the protein synthesis ( blocks attachment of aminoacyl tRNA to 30S subunit).  To know about this antibiotics you can visit the following links: http://en.wikipedia.org/wiki/Tetracycline http://en.wikipedia.org/wiki/Tetracycline_antibiotics http://www.drugs.com/tetracycline.html Fig: Tetracycline resistance

3) INHIBITION OF NUCLEIC ACIDS & PROTEIN SYNTHESIS : Streptomycin :  Streptomycin is an antibiotic(antimycobacterial) drug, the first class of drugs called aminoglycosides . It is derived from actinobacterium Streptomyces griseus.  It was first antibiotic remedy for tuberculosis. Streptomycin is a bactericidal antibiotic.    MECHANISM OF ACTION: Streptomycin is a protein synthesis inhibitor.  It binds to small 16S rRNA of 30S subunit of bacteral chromosome, interfering with the binding of formyl -methiontyl t-RNA to 30S subunit .  More on  http://en.wikipedia.org/wiki/Streptomycin . To know more please follow this links: http://www.rxlist.com/streptomycin-drug.htm http://www.webmd.com/drugs/drug-11249-streptomycin+im.aspx?drugid=11249&drugname=streptomycin+im http://livertox.nih.gov/Streptomycin.htm http://www.drugs.com/cdi/streptomycin.html

2). DAMAGE TO CYTOPLASMIC MEMBRANE :                                                              Certain antibiotics produced by Bacillus spp can cause the damage to cytoplasmic membrane & cause leakage from the cytoplasmic membrane of the cell. The antibiotics included are Polymyxins, Gramicidins, Tyrocidine, Polyenes . http://www.ncbi.nlm.nih.gov/pubmed/15508894 http://pathmicro.med.sc.edu/mayer/antibiot.htm http://voices.yahoo.com/antibiotics-four-ways-they-inhibit-microorganisms-2914969.html?cat= Polymyxin:  Polymyxins   are   a ntibiotics ,   with a general structure consisting of a cyclic   peptide   with a long   hydrophobic   tail. They disrupt the structure of the bacterial cell membrane by interacting with its   phospholipids . They are produced by   nonribosomal peptide   synthetase systems in   Gram-positive   bacteria such as   Paenibacillus polymyxa   and are selectively toxic for   Gram-negative   bacteria due to their specificity for the   lipopolysacc

1) INHIBITION OF CELL WALL SYNTHESIS :  Vancomycin : Vancomycin is a glycopeptide antibiotics produced by Streptomyces orientalis & used in prophylaxis & treatment of infections caused by Gram positive bacteria.   Vancomycin was first isolated in 1953 at  Eli Lilly , from a soil sample collected from the interior jungles of  Borneo  by a missionary. It is a naturally occurring antibiotic made by the soil bacterium  Actinobacteria   species  Amycolatopsis orientalis  (formerly designated  Nocardia orientalis ). It is a complex chemical compound and an example of a comparatively rare halo organic natural compound, containing two covalently bonded chlorine atoms.  The compound was industrially produced by fermentation and given the generic name  vancomycin , derived from the term "vanquish." The original indication for vancomycin was for the treatment of  penicillin -resistant  Staphylococcus aureus ,  a use kept alive for many years by the fact that compound ha

1) INHIBITION OF CELL WALL SYNTHESIS :  Cycloserine : It is produced by Streptomyces spp but it is now manufactured by chemical synthesis. It also inhibits cell wall synthesis( inhibition of pentapeptide side chain).  http://en.wikipedia.org/wiki/Cycloserine ,  ww.antimicrobe.org/drugpopup/Cycloserine.htm   http://www.netdoctor.co.uk/infections/medicines/cycloserine.html http://www.medicinenet.com/cycloserine_capsule_oral/article.htm

1) INHIBITION OF CELL WALL SYNTHESIS : Bacitracin :  It is produced by Bacillus subtilis.  Since it is toxic to animal or human cells it cannot be used for systemic chemotherapy. But it is used as skin ointments & is effective against Gram positive bacteria. It also inhibits cell wall synthesis( prevents regeneration of mono phosphate from pyrophosphate). To know visit this link: http://en.wikipedia.org/wiki/Bacitracin, http://www.webmd.com/drugs/drug-14270-bacitracin+top.aspx?drugid=14270&drugname=bacitracin+top, http://www.drugs.com/cdi/bacitracin-ointment.html.                                              Fig: Mode of action   Fig: Bacitracin as Ointment 

1) INHIBITION OF CELL WALL SYNTHESIS: Cephalosporins :  These are class of B-lactam antibiotics originally derived from a marine fungus Cephalosporium acremonium .  They are effective against Gram positive & Gram negative bacteria (Broad spectrum antibiotics).  Classification: The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their  antimicrobial  properties. The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended- spectrum  cephalosporins were classified as second-generation cephalosporins. Each newer generation has significantly greater  Gram-negative  antimicrobial properties than the preceding generation, in most cases with decreased activity against  Gram-positive  organisms. Fourth-generation cephalosporins, however, have true broad-spectrum activity.  Members Description 1 Cefacetrile  (cephacetrile),  Cefadroxil

MODE OF ACTION : 1.) INHIBITION OF CELL WALL SYNTHESIS:                                                                                 Antibiotics such as penicillins, cephalosporins, cycloserine, vancomycin, & bacitracin inhibits the biosynthesis of  Peptidoglycan. Penicillin : They are classes of   beta-lactam antibiotics ( are a broad class of  antibiotics , consisting of all antibiotic agents that contains a  β-lactam  ring in their molecular structures) which acts against Gram positive, some spirochetes & Gram negative diplococci. Penicillin was first discovered by Alexander Fleming in 1928 from Penicillium notatum . All the penicillin have basic structure of B-lactam nucleus & several attached groups. It blocks the cross linking of carbohydrate in peptidoglycan. This causes the formation of weak wall & thus the cell swells & bursts.(  http://en.wikipedia.org/wiki/Beta-lactam_antibiotic   http://en.wikipedia.org/wiki/Beta-lactamase ) Penicill