I understand bacteria have become resistant to antibiotics due to selection pressures, but how do resistant bacteria process antibiotics when exposed to it, compared to non-resistant bacteria. Also, what research is being conducted to combat bacteria resistant to antibiotics?

  • $\begingroup$ I suggested an edit for the title, the original one sounds like all bacteria are antibiotic-resistant. $\endgroup$ – nico Jan 7 '12 at 10:46
  • $\begingroup$ Similar questions could be asked for resistance in insects, "weeds", fungi... $\endgroup$ – user132 Jan 8 '12 at 1:42
  • $\begingroup$ @J.M. + cancer as well $\endgroup$ – jp89 Jan 8 '12 at 2:07

Bacteria usually gain resistance mechanisms through horizontal gene transfer (such as conjugation and phage infection). The four main mechanisms in which bacteria elude antibiotics are:

  1. Drug Inactivation: For example, E. coli can produce beta-lactamase that inactivate many lactam based antibiotics such as penicillin.
  2. Alteration of Target Site: Mutations in genes encoding for target sites can reduce drug binding affinity. Example: Random mutations in DNA gyrase and topoisomerase IV reduces binding affinity to fluoroquinolone.
  3. Alteration of Metabolic Pathways: Many drugs target certain parts of metabolic pathways by inactivating enzymes or sequestering substrates. Bacteria can use alternative metabolic pathways or find ways to uptake the necessary nutrients from the environment.
  4. Reduced drug accumulation: Caused by reduced drug permeability or the ability of the bacteria to transport drugs out of the cell (for example, tetA encodes for a tetracycline efflux transporter). They can gain these abilities through conjugation, phage infection (transduction), or uptake of environmental DNA (transformation).

Wikipedia has a pretty extensive and comprehensive article on antibiotic resistance. There's also a good list of references. http://en.wikipedia.org/wiki/Antibiotic_resistance


Also, what research is being conducted to combat bacteria resistant to antibiotics?

You've gotten some decent answers for how antibiotic resistance arises, so I thought I'd touch on this a bit. There's three major thrusts to anti-resistance research:

  1. Finding new targets and mechanisms. Essentially, creating new antibiotics that are subtly different enough that they slip past existing resistance mechanisms (usually by tacking a more elaborate side-group onto an existing antibiotic) or an entirely new class that targets a different mechanism to disrupt bacteria. This is essentially a drug development task, and is hard.
  2. Antimicrobial stewardship. This is largely clinical research examining how we use are existing antibiotics. Can we alter the duration/deployment/etc. of a course of antibiotics to minimize the chance of resistance. Can we minimize the number of times we use antibiotics inappropriately, giving rise to resistance with no gain to the patient?
  3. Alternate antimicrobial techniques. Can we use non-antibiotic techniques to prevent bacterial infections in the first place, or treat them when they occur? Antimicrobial surfaces, like copper or silver impregnated surfaces, improved surface cleaning, etc.
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    $\begingroup$ Another one for antimicrobial stewardship: it is somewhat interesting that some of the antibiotics used in animals have some similarity with antibiotics used in humans. There is a concern that animal pathogens that gain resistance to feed antibiotics can pass their resistance factors to human pathogens that haven't had the time to develop their own resistance factors. One offhand example I have is quinupristin/dalfopristin (one of the antibiotics tried when vancomycin can't cut it), which has structural similarity to the virginiamycins in animal feeds... $\endgroup$ – user132 Jan 8 '12 at 1:40

The lead question you have answered yourself: bacteria become resistant because of the selection pressure caused by the antibiotic's effective suppression of the original non-resistant bacteria. Those variants which resist the suppression are selected for as a natural consequence.

How do resistant bacteria process antibiotics? It depends on the details of the particular antibiotic, and perhaps the kind of resistance.

Take the case of penicillin and related antibiotics, like amoxicillin. These antibiotics act by inhibiting the formation of a layer of the cell wall which is essential for many kinds of bacteria. This prevents multiplication of the bacteria and contributes to their distruction. Wikipedia gives some details on the action of these β-lactam antibiotics.

Bacterial resistance to drugs like penicillin usually takes the form of the bacteria producing an enzyme (called β-lactamase) which breaks apart a ring in the drug molecule, disabling it and thus removing its effect on cell wall synthesis.

This resistance has become common because of the widespread use of penicillin-like drugs and because of transfer of the gene for it between bacteria species as by plasmids.

Researchers managed in the 70s to discover and develop an auxilliary weapon in this war. This was clavulanic acid, which has a structure partly similar to the penicillins and like them is attacked by the bacterial β-lactamase enzyme. Unlike the penicilins though, it forms a permanent bond with the enzyme molecule, disabling its activity. This has led to currently effective drugs like Augmentin which include in the same pill both amoxicillin and its protector, clavulanic acid.

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    $\begingroup$ The other route taken, of course, was to find β-lactams that are not degraded by enzymes that affect penicillins and cephalosporins. Two of these β-lactam classes are the carbapenems (e.g. imipenem, meropenem) and monobactams (e.g. aztreonam, tigemonam) $\endgroup$ – user132 Jan 7 '12 at 11:56
  • $\begingroup$ @J.M. and the route taken by bacteria is to evolve/select for beta-lactamases that have activity against carbapenems, like some of the lesser-prevalent (at present) class-D enzymes, thus ensuring a continuing source of funding for our lab. $\endgroup$ – Nick T Jan 8 '12 at 1:09
  • $\begingroup$ @Nick: Right. War never really ends, no? :( $\endgroup$ – user132 Jan 8 '12 at 1:40
  • $\begingroup$ @J.M. you're eluding to how calling it a "war" is a bit of a lie; reminds me of a guy on TotN talking about the "war on cancer" $\endgroup$ – Nick T Jan 8 '12 at 1:43
  • $\begingroup$ @Nick, sure, but you have to admit that coping with infectious diseases was treated like a "war" for the past few decades, what with the escalation of "improved" antibiotics. Would we have had to use glycopeptides like vancomycin if β-lactams were sufficient to keep the bacteria down? $\endgroup$ – user132 Jan 8 '12 at 1:48

Most resistance is acquired by horizontal transfer by various means

Conjugation is the sexual transfer

Transduction is transfer by viruses that integrate into the genome then when they are activated, they carry bits of the genome attached to their own to a new host

Transformation is the uptake of naked plasmid DNA into a new host

Transfection is similar to transduction and is viral mediated

And of course you have acquired which results from point mutations that alter the cells ability to be harmed by an agent, simple changes like change of the cellular membrane or receptor sites

  • $\begingroup$ thanks for your answer and efforts in the community... we always appreciate references to back up the information stated in answers as well as questions... do you thin you could add some links to help others follow your answer (I know some of this may be common knowledge to you, but citations and other sources - even webpages - are better than nothing). Also, you may want to check out the help site on "how to write a good answer" biology.stackexchange.com/help/how-to-answer $\endgroup$ – Vance L Albaugh Jul 9 '16 at 22:12

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