Exploring Bacteriocidal & Bacteriostatic Agents

[sameeralord]

Hello everyone,

Bacteriocidal- Example quinolones who inhibit DNA synthesis
Bacteriostatic- like aminoglycosides which inhibit protein synthesis

Now my question is bacteriocidal means bacteria must be killed, now if DNA synthesis is inhibited, the bacteria won't be able to replicate and create proteins. Ok the lack of protein would kill the bacteria.

Now bacteriostatic means prevention of bacterial growth. How can inhibiting protein synthesis not kill the bacteria, and how does it prevent bacterial replication.

Also what category does beta lactamases which inhibit cell wall syntheis fall into.

Thanks

 

[Curious3141]

Hello everyone,

Bacteriocidal- Example quinolones who inhibit DNA synthesis
Bacteriostatic- like aminoglycosides which inhibit protein synthesis

Now my question is bacteriocidal means bacteria must be killed, now if DNA synthesis is inhibited, the bacteria won't be able to replicate and create proteins. Ok the lack of protein would kill the bacteria.

Now bacteriostatic means prevention of bacterial growth. How can inhibiting protein synthesis not kill the bacteria, and how does it prevent bacterial replication.

Also what category does beta lactamases which inhibit cell wall syntheis fall into.

Thanks

Hi Sameera,

The fundamental difference between bactericidal antibiotics and bacteriostatic ones is that, with the former, the bacteria cannot continue to divide even when the drug is removed (they are now considered non-viable or "dead"). In contrast, with the latter, the bacteria don't divide while the drug concentration is high, but recover when the drug is removed, and continue to multiply as before.

In general, it's not so simple to decide if a given antibiotic is going to be bactericidal (that's the right spelling by the way) or bacteriostatic. Often, an in-vitro criterion is used, e.g. >99.9% killing of a defined bacterial inoculum in a defined time frame (often 24 hours) means the drug is bactericidal for those bacteria. Anything less is bacteriostatic. (Studies like these are called killing kinetics studies).

However, this is a fairly arbitrary criterion. Some drugs may be bactericidal to some bacterial genera, but only bacteriostatic to others. Some drugs may be classified as bacteriostatic, but may fulfill the bactericidal criterion at higher doses.

And the distinction may not be that relevant in the clinical context either. Generally, it's only considered "very important" to use bactericidal drugs in preference to bacteriostatic drugs when either a) it's a life-threatening infection, such as bacterial endocarditis or meningitis or b) the patient is very severely immunocompromised e.g. has very low numbers of a particular type of white blood cells (a condition called neutropenia) and likely won't be able to clear the infection without the "extra help". In these cases, bactericidal antibiotics are preferred. But in otherwise healthy people with less severe infections, bacteriostatic antibiotics are fine if there are other conditions favouring them (cost, ease of dosing, less toxicity (side effects)).

Going back to your question as to how a DNA replication inhibitor (the quinolone class) can be bactericidal, well, DNA replication is a critical point in the life-cycle of any organism (prokaryotic like bacteria or eukaryotic like us). A cell generally "commits" itself to cell division (which includes DNA replication as a critical component) and it can't reverse this "decision". If in the midst of replication, it "discovers" there's a spanner in the works (the quinolone inhibiting DNA gyrase and topoisomerase IV, which are indispensable enzymes governing DNA replication), then it "seizes" in the middle of cell division and basically becomes non-viable (dead). Remember that when it comes to bacteria, the permanent incapacitation of their ability to divide is considered death.

Protein synthesis is also an important cellular activity, but shutting it off for a while probably won't impair the organism permanently, especially if the proteins can last for some time and/or there are other metabolic pathways the organism can fall back upon. You must also remember that this is not an "all/none" thing - even with inhibition, some protein synthesis may still be able to continue in the background, albeit at a low level but sufficient to sustain bacterial life. When the block is removed (e.g by the drug being eluted out in-vitro, or metabolised by the human body in-vivo, the bacteria can resume "business as usual").

Beta-lactams like penicillins are almost always considered bactericidal. This is because they act on the cell wall of bacteria, which is the most important barrier against the "outside world". Without a functioning cell wall, the bacteria become vulnerable, and change into forms known as spheroplasts, which are osmotically fragile (they can easily take in water, swell and burst).

Hope this answers most of your questions.

 

[Ygggdrasil]

You may find the following paper to be useful: Kohanski et al. 2007. A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics Cell, 130: 797. http://dx.doi.org/10.1016/j.cell.2007.06.049

Abstract:
Antibiotic mode-of-action classification is based upon drug-target interaction and whether the resultant inhibition of cellular function is lethal to bacteria. Here we show that the three major classes of bactericidal antibiotics, regardless of drug-target interaction, stimulate the production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death. We also show, in contrast, that bacteriostatic drugs do not produce hydroxyl radicals. We demonstrate that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product of an oxidative damage cellular death pathway involving the tricarboxylic acid cycle, a transient depletion of NADH, destabilization of iron-sulfur clusters, and stimulation of the Fenton reaction. Our results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.

 

[sameeralord]

Thanks for both answers

@Curious3141- Your answer was very good. I understood the bactericidal part now but I still have a question about bacteriostatic drugs. Now definition of bacteriostatic means inhibit bacterial reproduction. I can see your point of it been reversible. Now my question is even though protein synthesis is inhibited, the bacteria can still replicate and divide using DNA replication, they won't be able to cause damage but they will still increase. So isn't this contradictory with the definition. Also you said with bactericial when the drug is removed, bacteria cannot divide. Eg if some bacteria survived quinolone attack won't they be able to replicate after drug is removed. Thanks!

 

[Curious3141]

Thanks for both answers

@Curious3141- Your answer was very good. I understood the bactericidal part now but I still have a question about bacteriostatic drugs. Now definition of bacteriostatic means inhibit bacterial reproduction. I can see your point of it been reversible. Now my question is even though protein synthesis is inhibited, the bacteria can still replicate and divide using DNA replication, they won't be able to cause damage but they will still increase. So isn't this contradictory with the definition.

No, because cell division does involve protein synthesis as well. Various enzyme and structural proteins have to be synthesised to drive the cell through the cycle and make enough material to populate the two daughter cells. You stop protein synthesis, you stop cell division, even if DNA replication is still able to proceed (and even DNA replication also needs proteins to proceed - remember that all the enzymes involved are proteins!).

Also you said with bactericial when the drug is removed, bacteria cannot divide. Eg if some bacteria survived quinolone attack won't they be able to replicate after drug is removed. Thanks!

The definition of bacterial killing is permanently removing their ability to divide. By that definition, the only bacteria that can "survive" a quinolone attack are those that are exposed to a sub-effective concentration (or for insufficient time), and those that have developed resistance mechanisms (or are intrinsically resistant) to the antibiotic. If a fully susceptible (no resistance mechanism) bacterium is exposed to an adequate concentration of the antibiotic for enough time, it has a very low chance of survival (<0.1%). Note that I didn't say zero, because almost nothing is an absolute in biology, and the definition of bactericidal agent uses >99.9% killing over 24 hours as the criterion.

The point is that the key difference between -cidal and -static drugs is that when you expose bacteria to both drugs and then elute them out, most bacteria cannot recover from the former, while most bacteria can recover from the latter.

 

[sameeralord]

Thanks I get it now.

 

[miosim]

... if DNA synthesis is inhibited, the bacteria won't be able to replicate and create proteins. Ok the lack of protein would kill the bacteria.

I am not sure how inhibition of DNA replication causes inhibition of protein vital for a bacterial cell survival

Hi Sameera,
... Going back to your question as to how a DNA replication inhibitor (the quinolone class) can be bactericidal, well, DNA replication is a critical point in the life-cycle of any organism (prokaryotic like bacteria or eukaryotic like us). A cell generally "commits" itself to cell division (which includes DNA replication as a critical component) and it can't reverse this "decision". If in the midst of replication, it "discovers" there's a spanner in the works (the quinolone inhibiting DNA gyrase and topoisomerase IV, which are indispensable enzymes governing DNA replication), then it "seizes" in the middle of cell division and basically becomes non-viable (dead). Remember that when it comes to bacteria, the permanent incapacitation of their ability to divide is considered death...

For a while I have been looking for an answer to whether inhibition of chromosome replication should cause cell death. Indeed DNA replication is a critical point in the life-cycle, probably because all processes in cells are interconected so inhibition of chromosome replication may cause cell death. However does it mean that propagation is critical for the survival of an individual cell.
What do we know about this connection?
Thanks.

 

[vbaulin]

For physicists may be interesting to know that there exist purely physical mechanisms of killing bacteria. For example, hydrophobic cicada wing surface has bactericidal properties:

These surfaces are not particularly efficient in repelling bacteria, but can kill bacteria by mechanical rupture of the cell wall due to adsorbtion on the array of pillars on the surface of cicada wings.

See details at http://softmat.net/2012/05/22/anti-microbial-materials/