Question

Penicillin-resistant strains of Neisseria gonorrhoeae produce a plasmid-coded β-lactamase, which degrades penicillin.

What are the structural and metabolic changes that they may render this organism resistant to other antimicrobial drugs. (10)

2.2 Discuss the difficulties faced by the researchers in developing an effective vaccine against Neisseria gonorrhoeae. (5)

Answer 1

First of all, Neisseria gonorrhoeae is a gram negative diplococcus, which have the ability to live on or create colonies on the epithelial layer of our skin. It is a sexually transmitted disease (STD) and can affects urethra, cervix in females, pharynx, rectum and can cause conjuctivities as well.

As we all know, every foreign material which enters our body, is identified by our immune system and is characterized as friendly or non-friendly. The ones which are not friendly are tagged and antibodies are produced against them and made sure that they are destroyed and thrownout of our body.

How our body finds out if the material is friendly or non-friendly is a whole new topic which I will not discuss here, but just for understanding, the immune system recognizes the outer layer of every material. In our case here, the bacteria's outer layer which consists of various kinds of proteins are used to identify and tag. Also create a memory of that particular outer coating so that in case the similar bacteria entered our body next time our body immediately responds to it without doing a reasearch to find out what antibodies are necessary to destroy the bacterial cell.

On the contrary, the genetic make up of every organism decides its features. The proteins present on the outer coating of and bacterial cell is due to its genetic make up. This also contributes the pore size of the outer layer of the bacterial cell, which allows various components from external environment to pass inside the cell. The researchers take into considerations of this genetic make up, find out the porosity and the sites or structures on the bacterial cell which can be attacked so as to destroy them. Based on this knowledge, the pharma drugs are designed specifically to act on various kinds of bacterias and viruses as well.

In a similar fashion, the bacterial proteins have the property of identifying the drug and deactivating it.

In case of and not limited to N. gonorrhoeae, the bacterial genome has the property of going under mutations. These mutations allow the formation of new structural and functional proteins which are different than previous. i.e. now they have a different conformation, a different kind of active site and other properties like the changed porosity of the membrane. This leads to failure of the past designed drugs, which is known as drug resistance by bacteria.

Penicillin has the property of binding to a bacterial protein which is repsonisble to bind to peptides and create a bacterial wall. Penicillin attaches the active site of this protein which leads to unavailability of site where a peptide can bind and form a layer, which leads to non formation of the layer and thus destroying the cell.

Other similar drugs, e.g. cephalosporins, cephamycins etc are characterized as β-lactam antibiotics. They have a closed four-atom ring (formed of C,N) known as β-lactam ringwhich is the active site of the drug.

The plasmid-coded β-lactamase, produced by plasmid present in the bacterial cell, have the property of breaking this ring by hydrolysis and thus making the drug ineffective. As mentioned above, the mutations lead to changes in structural properties of a protein, in this case β-lactamase, which leads to ineffectiveness of a drug which previously destroyed the cell.

The other reason mentioned earlier, the porosity of the membrane also leads to lowering down the efficiency of the drug, since the amount of drug passed inside the bacterial cell, reduces or is not at all selected to be passed inside the cell making it ineffective.