Question

	a) Describe two different mechanisms by which bacteria can simultaneously acquire resistance to multiple antibiotics of different classes.

b) New point-of-care molecular tests are appearing that will rapidly distinguish between bacterial and viral infections, and in most cases identify the strain if it is bacterial. How will these tests improve antibiotic stewardship? (give an example if you can think of one)

d)  Metronidazole acts by making breaks in DNA strands. DNA breaks are mutagenic, and most mutagens are potential carcinogens. Why then is metronidazole not considered too toxic for use in humans? (explain)

Answer 1

Ans: a) There are many mechanisms to develop multiple antibiotic resistance by a given bacteria. Drug modification or inactivation: Based on the drug exposure by bacteria bacteria produce altered enzymes to add or delete some of the functional groups on the drug molecule either in periplasmic space or in cytoplasm and rendering the multiple drugs ineefective.

Drug efflux: Based on the antiobiotic signal or substrate signal bacteria can alter the porin channel by adding or delating some functional groups there by making porins highly effecient in pumping out or effluxing multiple antibiotics simultaniously. Here drug is active but it cannot reach the intended target and will be pumped out immediately.

b) Rapid chip antibody based or PCR based point-of-care molecular tests reducing the time by detecting molecular markers specific to bacterial and viral infections and also reducing the antibiotic burden on the patients. If the infection is from particular bacterial we can administer single antibiotic suitable for that bacteria instead of administering multiple antibiotics and antivirals purely by guess work.

For example a patient arrives with long term complaints like abdominal pain, nausia, intermittent frequent fevers, loss of appetite, frequent bloating and burping, weight loss etc. His stool sample extract can be tested within hours using specific antibodies for Helicobacter pylori infection or within hours PCR can be performed to find DNA markers. If he is positive for the tests he can be immediately administered with a single drug like metronidazole which is effective for anaerobic bacteria like H. Pylori.

d). Metronidazole (MTZ) is an antibiotic used both for bacteria and protozoal infections MTZ is highly active under anaerobic and reducing environment hence can kill effectively anaerobic organisms. It is activated when reduced through electron donation from ferredoxin or flavodoxin that were themselves reduced by the pyruvate- ferredoxin oxidoreductase (POR) possibly forming an hydroxylamine (occurs under strongly reducing conditions) Activated MTZ is thought to interact directly with DNA and the resultant complex can no longer function as an effective primer for DNA and RNA polymerases. Usually human have oxidative type of metabolism and our cells cannot operate under hypoxic conditions, where as bacteria in wounds or in the biofilms have hypoxic conditions (let’s say can survive as facultative) hence this drug can be effective against the anaerobic organisms or anaerobic reducing conditions. Most of the drugs acts based on the residence time, here MTZ half life is found to be 8 hours in 8 hours it can kill most of the bacteria under anaerobic conditions and not affecting the human cells. Hence metronidazole not considered too toxic for use in humans.