Antibacterial

To understand antibacterial it is important to first understand bacteria.

** BRIEF OVERVIEW OF BACTERIA: ** ** Definition: ** microscopic organisms of single cell with a protective wall made up from sugars covalently bonded to peptides and associated with lipids. Some bacteria cause diseases while others are beneficial. ** Some types of bacteria: ** // Aerobic bacteria // : infect surface areas like the skin and respiratory tract. // Anaerobic bacteria: // multiply in environments of little or no oxygen such as the bowel.


 * Morphology of bacteria:**
 * ** bacilli ** : rod-shaped
 * ** cocci ** : spherical
 * ** spirilla ** : curved walls

** ANTIBACTERIAL **

IB OBJECTIVES:
 * || ASSESSMENT DETAILS || OBJ. ||
 * D.6.1 || Outline the historical development of penicillins || 2 ||
 * D.6.2 || Explain how penicillins work and discuss the effects of modifying the side-chain || 3 ||
 * D.6.3 || Discuss and explain the importance of patient compliance and the effect of penicillin over-prescription. || 3 ||

** Antibacterial Definition: ** Chemicals used to restrain or prevent the growth and multiplication of bacteria. They are usually used to treat infections (caused by bacteria). Antibacterial are commonly used as a synonym for antibiotics. However, the latter cover a broader spectrum of antimicrobial compounds.

** Use ** (4 mechanisms): 1. By interfering with the enzymes that bacteria use to create normal cell walls and thus affecting the cell wall synthesis of bacteria. This causes the cell to swell and the osmotic pressure leads to the disintegration of the weakened cell wall. 2. By affecting the cell membrane 3. By inhibiting DNA synthesis 4. By inhibiting Protein synthesis.

// Main Classification of Antibacterial compounds: // // ( //// []) //


 * ** Bactericidal ** || ** Bacteriostatic ** || ** Narrow-spectrum ** || ** Broad-spectrum ** ||
 * // Kills the bacteria directly. //

Acts by altering the cell wall formation of bacteria, leading to weak wall and their further disintegration (e.g. Pencicillin) – See Use # 1. || // Kills bacteria indirectly. //

Slows the growth of bacteria, allowing the human body’s immune system to destroy the bacteria. (e.g. tetracyclins) || Kills a small number of species of bacteria. // Very specific: // act on one molecule that is specific to a certain type of bacteria || Kills a wide range of species of bacteria. // Not specific: // act on structures common to many types of bacteria such as the cell wall. ||


 * PENICILLIN **

//__ First record of penicillin growth on bacteria: __// Clodomir Picado Twight (1887-1944 ; Costa Rica) //__ Discovery Attributed to: __//__ Alexander __ Fleming (1881-1995 ; Scottland) //__ Discovery and Development: __// The Bacteriologist Fleming was working with cultures of Staphylococcus aureus trying to find a way to kill bacteria’s that infected wounds. During the holidays he accidentally left a Petri dish containing one of these cultures open. When he returned, he discovered that the mould (Penicillium notatum) that was growing on the bacterium was restraining its growth. He then deduced that this mould creates an efficient antibacterial compound (Penicillin). Howard Florey (1898-1968 ; Australia) and Ernst Chain (1906-1979 ; Germany) pursued Fleming’s discovery. They were able to isolate and purify penicillin. They used it for the first time in 1941 on a policeman who was dying of blood poisoning. In the 1950’s the chemical structure of penicillin was determined.
 * History: **

Like any other bactericidal antibiotic, Penicillin interferes with the enzymes necessary for bacteria to create normal cell walls. This creates weak walls which lead to the disintegration of bacteria due to osmotic pressure (See Use # 1)
 * How Penicillin works: **
 * // Note: //** Effective against Gram-positive organisms. Lack of action against most Gram-negative organisms.

There are different types of Penicillin. However, they all share a main structure called the beta-lactam ring which is a functional ground made up from four-member ring containing a nitrogen atom.
 * Penicillin Basic Structure: **
 * // Note: //** The Beta-lactam ring causes an antibiotic to be bactericidal (destroy the bacteria’s cell wall). Antibacterial substances containing this compound are most commonly used.

The picture above shows two types of Penicillin. They both contain the beta-lactam ring (highlighted in red).

** Classification of Penicillins ** ([])

There are 4 classes of penicillins, based upon their ability to kill various types of bacteria:
 * ** Natural Penicillins ** (Penicillin G, Procaine, Penicillin G, Penicillin V, Benzathine). The natural penicillins were the first agents in the penicillin family to be introduced for clinical use. The natural penicillins are based on the original penicillin-G structure. They are effective against gram-positive strains of streptococci, staphylococci, and some gram-negative bacteria such as meningococcus.

The structure of Penicillin G is shown in the picture above.
 * ** Penicillinase-Resistant Penicillins ** (Cloxacillin, Dicloxacillin) The penicillinase-resistant penicillins have a more narrow spectrum of activity than the natural penicillins. Their antimicrobial efficacy is aimed directly against penicillinase-producing bacteria.


 * ** Aminopenicillins ** (Ampicillin, Amoxicillin, Bacampicillin). The aminopenicillins were the first penicillins discovered to be active against gram-negative bacteria (such as E. coli and H. influenzae).

http://ezinearticles.com/?Penicillin-Antibiotics-Classification---Uses-and-Side-Effects&id=401820
 * ** Extended Spectrum Penicillins ** (sometimes called anti-pseudomonal penicillins)

The side chains of Penicillin (those attached to the beta-lactam ring) may be altered in order to produce Penicillin compounds that are effective against specific types of bacteria. Mainly Pencillin is altered to work against the penicillinase enzyme (a type of Beta lactamase enzyme that bacteria produce to resist beta-lactam anitbiotics) Over time, Penicillin has been used indiscriminately. It has been overprescribed and used in animal feedstock (food provided to animals). This in turn has allowed several bacteria to mature and become extremely resistance to penicillin (e.g. Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis).
 * Modifications of Penicillin **

1. Penicillin G was the first antibiotic used to fight infections. The structure of this antibiotic is as follows: (a) Determine the molecular formula of penicillin G. (b) State **two** reasons for modifying the side chain in penicillin G  (c) Explain the difference between broad-spectrum and narrow-spectrum antibiotics. (d) Describe the mode of action of penicillin in preventing the growth of bacteria. (e) Discuss **two** effects of the over-prescription of penicillin to humans.
 * PRACTICE IB QUESTIONS **


 * TWO DISTINCT CLASSIFICATION OF BACTERIA:
 * 1. Gram-negative bacteria** are [|bacteria] that do not retain [|crystal violet] dye in the [|Gram staining] protocol.[|[][|1][|]] In a Gram stain test, a [|counterstain] (commonly [|safranin]) is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color. The test itself is useful in classifying two distinct types of bacteria based on the structural differences of their [|cell walls]. [|Gram-positive bacteria] will retain the crystal violet dye when washed in a decolorizing solution.


 * 2. Gram-positive** [|bacteria] are those that are stained dark blue or violet by [|Gram staining]. This is in contrast to [|Gram-negative bacteria], which cannot retain the crystal violet stain, instead taking up the [|counterstain] ([|safranin] or [|fuchsine]) and appearing red or pink. Gram-positive organisms are able to retain the crystal violet stain because of the high amount of [|peptidoglycan] in the [|cell wall]. Gram-positive cell walls typically lack the outer membrane found in [|Gram-negative bacteria].

Sources: http://en.wikipedia.org/wiki/Gram-negative_bacteria http://en.wikipedia.org/wiki/Gram-positive_bacteria