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This is multipart series on antibiotic resistance in bacteria.

Check out the previous bits:

1. A primer on antibiotic resistance

2. Natural vs. synthetic drugs

Eventually, we’ll reach the ways in which bacteria develop antibiotic resistance, but before we get there, we’ll spend a little more time on antibiotics themselves.

What have we learned so far?

1. Antibiotics are natural products, made by bacteria and some fungi.
We have also learned about the difference between antibiotics and synthetic drugs. There isn’t always a clear distinction since chemical groups can be added to antibiotics, making them partly synthetic and partly natural.

2. Antibiotics are a chemically diverse group of compounds.
Antibiotics are not DNA. Neither are they proteins, although some antibiotics contain amino acids, which are the building blocks of proteins. In a way, antibiotics are kind of luxury molecules, since they aren’t essential for life. Bacteria don’t even make them until the population reaches a certain density and phase of growth.

Even though we can describe all antibiotics with a single word, there is no single description that does justice to these fascinating compounds.

We can group antibiotics into classes, either by chemical similarity – peptide antibiotics all contain amino acids held together by peptide bonds, ß-lactams all have a ß lactam ring – by the range of organisms they can kill – broad spectrum antibiotics kill a wide variety of bacteria, where narrow spectrum antibiotics have more specific targets; or by the metabolic pathway that they target.

Perhaps the easiest way to categorize antibiotics is by the organisms that produce them. Even there, antibiotics defy easy groupings. The majority are made by denizens of the dirt, but both fungi and bacteria get into the act.

But what do antibiotics do? How do they fulfill their role as agents of warfare?

They do kill bacteria – but how? In a bacterial population, do all members get killed?

Unfortunately, no, many antibiotics work by preventing bacterial growth. This means that most antibiotics only kill growing bacteria.

They keep bacteria from getting bigger?

No.

When we talk about animals, plants, or people growing, we’re really describing individual organisms getting larger. But, when we talk about bacterial growth, we’re referring to the size of a bacterial population and not just the size of a cell.

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In order for bacteria to grow, then, they need to make all the parts necessary for building new bacterial cells. DNA must be copied. New RNA, ribosomes, and proteins must be made. Cell walls must be built. Membranes have to be synthesized. And, then, of course the cells must divide.

Many, if not most, antibiotics act by inhibiting the events necessary for bacterial growth. Some inhibit DNA replication, some, transcription, some antibiotics prevent bacteria from making proteins, some prevent the synthesis of cell walls, and so on. In general, antibiotics keep bacteria from building the parts that are needed for growth.

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There are some antibiotics that act by attacking plasma membranes. Most antibiotics, though, work by holding bacterial populations in check until the immune system can take over.

This also brings us, to our first mechanism of antibiotic resistance. Persistance is resistance.

If bacteria need to grow in order to be killed by antibiotics, then bacteria, can escape from antibiotics, by NOT growing or by growing very slowly.

This phenomenon has been observed with biofilms (colonies of bacteria living on a surface) (1), E. coli in urinary tract infections (2), and most notably in the slow growing bacteria, that cause tuberculosis, Mycobacterium tuberculosis, and leprosy, Mycobacterium leprae (3).

It seems funny to think that not growing can be a mechanism for survival. But if you’re a bacteria, and you can hang around long enough in an inactive, non-growing state, enventually your human host will stop taking antibiotics, they will disappear from your environment and you can go back to growing.


References
:

1. P.S. Stewart 2002. “Mechanisms of antibiotic resistance in bacterial biofilms.” Int J Med Microbiol. 292(2):107-13.

2. Trlzsch K, Hoffmann H, Keller C, Schubert S, Bader L, Heesemann J, Roggenkamp A. 2003. “Highly Resistant Metabolically Deficient Dwarf Mutant of Escherichia coli Is the Cause of a Chronic Urinary Tract Infection.” J Clin Microbiol. 41(12): 5689-5694.

3. Gomez JE, McKinney JD. 2004. Tuberculosis (Edinb). 84(1-2):29-44.

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Comments

  1. #1 chezjake
    December 30, 2006

    Now that so much more of the biochemistry of antibiotic action is known, things seem to be much more complex. Back in the old days (1960-1970) when I worked for big pharma, antibiotics were termed to be either “bacteriocidal” — those that actually killed susceptible bacteria — or “bacteriostatic” — those that prevented them from reproducing, like the tetracyclines.

  2. #2 KevinC
    December 31, 2006

    Sandra,

    For natural sources of antibiotics you say;

    “The majority are made by denizens of the dirt, but
    both fungi and bacteria get into the act.”

    What other dirt denizens other than fungi and bacteria get into the act? And don’t we get some from plants as well (I should know that but don’t)?

  3. #3 Sandra Porter
    January 2, 2007

    I guess i shouldn’t have been so specific about dirt. It seems that molecules with bacterial-killing activity are made by many things inluding plants, moths, and people.

  4. #4 Organic Chemistry
    February 22, 2007

    this is an interesting discussion. In my opinion, the best antibiotics will come from synthetically-created antibiotic derivatives that are more resistant to degradation.

  5. #5 Sandra Porter
    February 22, 2007

    I think that’s absolutely true. In order for bacteria can make an antibiotic, they must also posess a means for antibiotic resistance.

  6. #6 Erin
    December 9, 2009

    I’m doing a project for school. I’m taking biology and chemistry, and to meet a standard for this project on a virus I would like to include something about enzymes. Do antibiotics attack the enzymes of the bacteria?

  7. #7 Sandra Porter
    December 9, 2009

    Hi Erin,

    Different antibiotics inhibit growth in different ways. Some antibiotics, like penicillin, work by blocking the enzymes that build cell walls. Other antibiotics work by blocking the ability of ribosomes to make proteins. And, other antibiotics prevent cells from making or repairing DNA.

  8. #8 Rebecca
    April 27, 2010

    Are there ever times where antibiotics can’t block the enzymes (reason as to why a zone of inhibition may not be present)?

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