Bacterial Antibiotic Resistence: Example Of Evolution ?

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Introduction      

BACTERIAL VARIATION

Any change in the genotype of a bacterium or its phenotype is known as variation. Genotypic variation can occur as a result of changes in the genes by way of mutation, loss or acquisition of new genetic elements.
These variations are heritable. Phenotypic variations are seen temporarily when bacteria are grown under certain environmental conditions. These variations are not heritable.

Heritable variations: 
Mutation:
A gene will mutate spontaneously, about once in a hundred million cell divisions. Such bacteria are called mutants. Most of these mutants die, but a when a mutant can adapt itself to the environment more readily; it may emerge as a new variant. Chromosomal mutations may lead to Emergence of drug resistance in bacteria. Examples include methicillin resistance in Staphylococcus aureus, Multi-drug resistance in Mycobacterium tuberculosis.

Mechanisms of horizontal gene transfer (HGT) in bacteria
Transformation:
Some bacteria have ability to uptake naked DNA fragment from the surrounding environment. When such a DNA confers new property to the bacterium, it is termed transformation. Change from R form of Streptococcus pneumoniae to S form as demonstrated by Griffith is due to transformation.

Conjugation:
Transfer of genetic material (usually plasmids) from one bacterium to another through the mediation of sex pili. Any property that is coded on a transmissible plasmid can be transferred to a recipient bacterium. Properties such drug resistance mediated by beta-lactamases, bacteriocin production etc can be transferred by conjugation.

Transduction:

Transfer of genetic material through mediation of bacteriophage is known as transduction. Only those strains of Corynebacterium diphtheriae that are infected by a beta phage are toxigenic. Change in O antigen in Salmonella (S. anatum->S. newington-> S.minneapolis) is because of lysogenic phage.

Transposition:
Variations in the flagellar antigens in Salmonella are due to transposons. Similar gene rearrangements may result in antigenic variations, as in Neisseria gonorrhoeae and Borrelia recurrentis. 

Non-heritable variations: 
A variation in the phenotype of a microorganism, where the genetic constitution remains unchanged is a non-heritable variation. Such variations are seen due to a change in environmental conditions and such variations are neither permanent nor heritable. They may revert back to normal state when the conditions are restored.
Some examples are:

• Loss of flagella in S.typhi when grown in phenol agar (H-O variation)
• Pleomorphism (variation in shape) in old cultures
• Lack of pigment production by S.aureus in anaerobic conditions
• Formation of spheroplasts and protoplasts
• V-W variation in Salmonella typhi that is characterized by loss of Vi antigen
• S-R variation in Salmonella typhi that is characterized by loss of O antigen and change in colony morphology to rough type.
• Production of flagella in Listeria monocytogenes occurs at temperature less than 20^oC

  Last edited in June 2006 http://www.microrao.com/micronotes/variation.htm

http://textbookofbacteriology.net/resantimicrobial_3.html

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Mechanism of resistance:

        
        1. Antibiotic,   2. Bacteria unable to resist the antibiotic,   3.Bacterium that are not sensitive to the antibiotic,   4. Bacterium that escaped,   5. Dead bacterium,   6. Bacterium with improved resistance,   7. A rather resistant bacterial group

http://www.biomedcentral.com/1741-7007/8/123

Table  Mechanisms of resistance

Adapted from Opal SM, Medeiros AA. Molecular mechanisms of antibiotic resistance in
bacteria. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and
Practice of Infectious Diseases, 6th ed. Philadelphia, PA; Elsievier
Churchill, Livingstone Inc. 2005;(1):253-270.
¹GNRs — Gram-negative rods ²ESBLs — extended-spectrum-β-lactamases ³GPC — Gram-positive cocci
⁴PBP — penicillin-binding protein ⁵DHPS — dihydropteroate synthesis ⁶DHFR — dihydrofolate reductase

http://www2.mlo-online.com/features/201105/cover-story/the-anarchy-of-antibiotic-resistance-the-mechanisms-of-bacterial-resistance.aspx

 

Mechanisms of antibiotic resistance in Staphylococcus aureus

• enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes),
• alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains),
• trapping of the antibiotic (for vancomycin and possibly daptomycin)
• efflux pumps (fluoroquinolones and tetracycline).

Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection.

http://www.ncbi.nlm.nih.gov/pubmed/17661706

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Natural occurance

There is evidence that naturally occurring antibiotic resistance is common. The genes that confer this resistance are known as the environmental resistome. These genes may be transferred from non-disease-causing bacteria to those that do cause disease, leading to clinically significant antibiotic resistance.

• In 1952 an experiment conducted by Joshua and Esther Lederberg showed that penicillin-resistant bacteria existed before penicillin treatment. While experimenting at the University of Wisconsin-Madison, Joshua Lederberg and his graduate student Norton Zinder also demonstrated preexistent bacterial resistance to streptomycin.
• In 1962, the presence of penicillinase was detected in dormant Bacillus licheniformis endospores, revived from dried soil on the roots of plants, preserved since 1689 in the British Museum.
• Six strains of Clostridium, found in the bowels of William Braine and John Hartnell (members of Franklin Expedition) showed resistance to cefoxitin and clindamycin. It was suggested that penicillinase may have emerged as a defense mechanism for the bacteria in their habitats, as in the case of penicillinase-rich Staphylococcus aureus, living with penicillin-producing Trichophyton. This, however, was deemed circumstantial. Search for a penicillinase ancestor has focused on the class of proteins that must be a priori capable of specific combination with penicillin. The resistance to cefoxitin and clindamycin in turn was speculatively attributed to Braine's and Hartnell's contact with microorganisms that naturally produce them or to random mutation in the chromosomes of Clostridium strains.

Nonetheless there is an evidence that heavy metals and some pollutants may select for antibiotic-resistant bacteria, generating a constant source of them in small numbers.

http://en.wikipedia.org/wiki/Antibiotic_resistance#Natural_occurrence

 

Dr. Daniel Criswell ( Ph.D. in Molecular Biology) wrote in The "Evolution" of Antibiotic Resistance:

 

"Penicillin is an antibiotic produced by the common bread mold Penicillium that was discovered accidentally in 1929 by the British microbiologist, Alexander Fleming. By the 1940s, penicillin was available for medical use and was successfully used to to treat a wide range of infections. In 1967 the first penicillin-resistant Streptococcus pneumoniae was observed in Australia.

Since then, many more antibiotics isolated from fungi (molds) and bacteria have been used to treat a wide range of human and animal infections.

One group of bacteria, the Streptomyces, produces most of the medically important antibiotics.Streptomyces release antibiotics into the soil in a sort of "biochemical warfare" scenario to eliminate competing organisms from their environment. These antibiotics are small molecules that attack different parts of an organism's cellular machinery. Streptomyces-produced quinolone and coumarin antibiotics, such as novobiocin, interfere with a protein called gyrase that assists in the normal separation of double-stranded DNA during replication of DNA or transcription of messenger RNA. Failure of DNA to properly separate during these processes results in a bacterium not being able to divide normally or produce functional proteins. Ribosomes, the structures where protein synthesis is catalyzed, are the targets of many other Streptomyces antibiotics such as spectinomycin, tetracycline, and streptomycin. Spectinomycin and tetracycline prevent proteins from being assembled by the cell and streptomycin induces the assembly of the wrong amino acids into the translated protein. Without proteins, which are necessary for normal cell function, the cell dies. The slight differences between human ribosomes which are not bound by these antibiotics and bacterial ribosomes make this type of antibiotic ideal for treating many illnesses.

Other antibiotics, such as penicillin, block the assembly of the bacterial cell wall causing it to weaken and burst. Penicillin is an effective antibiotic for human diseases because it interferes with a biological component in bacteria (cell wall) not found in human cells.

The production of antibiotics by these organisms provides them with a competitive advantage over non-resistant bacteria in their environment. Just as large organisms such as plants and animals must compete for living space, food, and water, these microbes use antibiotics to eliminate competition with other microbes for these same resources.

However, not all bacteria are defenseless against the antibiotic producers. Many possess genes that encode proteins to neutralize the affects of antibiotics and prevent attacks on their cell machinery.
Efflux pumps, located in the cell membrane, are one method of protection that many bacteria use against the influx of antibiotics. The offensive antibiotic is pumped out of a cell that possesses these pumps before the antibiotic can cause harm to the cellular machinery. Although many efflux pumps may be specific for the substrate they pump out of the cell, they are not uncommon. Ribosomal protection proteins (RPP) are another source of resistance bacteria use to protect themselves from antibiotics. These proteins protect ribosomes by binding them and changing their shape or conformation. The change in the ribosome shape prevents an antibiotic from binding and interfering with protein synthesis. The RPP-bound ribosomes are able to function normally during protein synthesis, an important feature of this method of antibiotic resistance. Some bacteria produce enzymes that neutralize antibiotics by adding acetyl (COCH3) or phosphate (PO32-) groups to a specific site on the antibiotic.This modification reduces the ability of the antibiotic to bind to ribosomes, rendering it harmless to the cell.

Interestingly, all three types of antibiotic-resistant genes that produce efflux pumps, ribosomal protection proteins, and modifying enzymes are found in Streptomyces species, the producers of many antibiotics. It appears this is the method Streptomyces uses to protect itself from its own antibiotics.

 

Is it possible to transfer these resistance genes to other bacteria?

A unique bacterial characteristic that has not been demonstrated in plant and animal cells is the ability to transfer genes from one bacterium to another, a process called lateral gene transfer.

Ironically, several antibiotic resistance genes found in other pathogenic bacteria are very similar in DNA sequence to the genes found in Streptomyces species.(Benveniste, R., and J. Davies, 1973. Aminoglycoside antibiotic-inactivation enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proceedings of the National Academy of Sciences USA 172:3628-3632) The efflux pumps that Streptomyces use to pump out antibiotics to eliminate their competitors are likely the same pumps that other species of bacteria are now using to pump out the offensive antibiotic delivered from Streptomyces! The antibiotic-resistant bacteria likely have acquired the genes for these efflux pumps through lateral gene transfer.

The presence of ribosomal protection proteins and antibiotic modifying enzymes in resistant bacteria has also likely originated from Streptomyces or some other antibiotic-producing microbe.(Chopra, I., and M. Roberts, 2001. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiology and Molecular Biology Reviews 65(2):232-260. )

This allows a species of bacteria to possess enough genetic variability to adapt to a changing environment and to compete with its neighbors. (This method of defense is very similar to the genetic variability of mammalian antibody-producing B lymphocytes) The bacterium that acquires the antibiotic resistance genes still has the physical and metabolic qualities that distinguish it from other bacteria kinds and associates it with its own kind of bacteria. The observed increase in the frequency of antibiotic-resistant bacteria has resulted from the increased use of antibiotics in medicine and agriculture, resulting in the reduction of organisms that do not possess antibiotic resistance genes."

 

"But, horizontal transfer merely involves the transfer of resistance genes already present in the bacterial world.
While horizontal acquisition of resistant genes is “beneficial” to those bacteria exposed to a given antibiotic, such gene transfer does not account for the origin or the diverse variety of these genes.  As such, it fails to provide a genetic mechanism for the origin of any antibiotic resistance genes in the biological world.  Evolution, through the process of common “descent with modification,” predicts it can account for the origin and diversity of life on earth; however, the mere shuffling of pre-existing genes between organisms via gene transfer does not provide the necessary genetic mechanism to satisfy this prediction.  Nor can it readily account for the simultaneous development of both the antibiotic biosynthesis and resistance genes—an evolutionary enigma (Penrose, 1998).  Thus, horizontal transfer of resistant genes cannot be offered as an appropriate example of “evolution in a Petri dish.”(Kevin Anderson, Ph.D, microbiology)

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Mutations

Mutations, defined as any changes in the DNA sequence (Snyder and Champness, 2003), provide the only known genetic mechanism for producing new genetic activity and function in the biological world.  In light of this, only mutations have the potential to provide evolution a mechanism that accounts for the origin of antibiotic resistance.  Thus, only that resistance resulting from a mutation is a potential example of “evolution in action” (i.e., common “descent with modification”).

 

In the presence of a particular antibiotic (or other antimicrobial), any mutation that protects the bacterium from the lethality of that compound clearly has a “beneficial” phenotype.  Natural selection will strongly and somewhat precisely select for those resistant mutants, which fits within the framework of an adaptive response.  But, molecular analysis of such mutations reveals a large inconsistency between the true nature of the mutation and the requirements for the theory of evolution (Table I).

Bacterial resistance to the antibiotic, rifampin, can result from a commonly occurring spontaneous mutation.  Rifampin inhibits bacterial transcription by interfering with normal RNA polymerase activity (Gale et al., 1981; Levin and Hatfull, 1993).  Bacteria can acquire resistance by a point mutation of the ß-subunit of RNA polymerase, which is encoded by the rpoB gene (Enright et al., 1998; Taniguchi et al., 1996; Wang et al., 2001; Williams et al., 1998).  This mutation sufficiently alters the structure of the ß-subunit so that it loses specificity for the rifampin molecule.  As a result, the RNA polymerase no longer has an affinity for rifampin, and is no longer affected by the inhibitory effect of the antibiotic.

 

In fact, the level of rifampin resistance that a bacterium can spontaneously acquire can be extremely high.  In my laboratory, we routinely obtain mutant strains with a resistance level that is orders of magnitude greater than that of the wild-type strain.  When rifampin is present, this mutation provides a decided advantage for survival compared with those cells lacking these specific mutations.  But, each of these mutations eliminates binding affinity of RNA polymerase for the rifampin.  As such, these mutations do not provide a mechanism accounting for the origin of that binding affinity, only its loss.

Spontaneous resistance to fluoroquinolones (such as ciprofloxacin or norfloxacin) is also a frequent mutation in some bacteria.  The primary target of the antibiotic is the enzyme, DNA gyrase, which is comprised of two proteins encoded by the genes, gyrA and gyrB (Hooper and Wolfson, 1993).  Genetic analysis has found that resistance to this class of antibiotics can result from a point mutation in either of these genes (Barnard and Maxwell, 2001; Griggs et al., 1996; Heddle and Maxwell, 2002; Heisig et al., 1993, Willmott and Maxwell, 1993). These mutations of the gyrase subunits apparently cause a sufficient conformational change to the gyrase so that its affinity for the fluoroquinolones is reduced or lost (Figure 1).  Again, despite their “beneficial” nature, these mutations provide no useful model that explains the origin of the gyrase’s affinity for the fluoroquinolones.

Figure 1.  Mechanism of ciprofloxacin resistance.
(A) Ciprofloxacin interacts with gyrase, inhibiting its enzymatic activity.  (B) A mutation in either of the genes, gyrA or gyrB, can change the conformational structure of gyrase, and reduce the binding affinity of the enzyme for ciprofloxacin.  This results in an inability of the antibiotic to inhibit the gyrase, and the cell becomes resistant to the antibiotic.

 

Resistance to streptomycin can also result from spontaneous bacterial mutations.  In this case, streptomycin blocks bacterial protein synthesis apparently by binding to the 16S rRNA segment of the ribosome and interfering with ribosome activity (Carter et al., 2000; Leclerc et al., 1991).  Resistance to the antibiotic can occur by mutations in the 16S rRNA gene, which reduces the affinity of streptomycin for the 16S molecule (Springer et al., 2001).  Reduction of specific oligopeptide transport activities also leads to spontaneous resistance of several antibiotics, including streptomycin (Kashiwagi et al., 1998).  In these examples, resistance occurred as a result of the loss of a functional component/activity.

 

Loss of enzymatic activity can result in metronidazole resistance. Interacellular metronidazole must be enzymatically activated before it can serve as an antimicrobial agent.  This activation is achieved by the enzyme, NADPH nitroreductase (Figure 2).  If the metronidazole is not activated it has no inhibitory effect on the bacterium.  Thus, if NADPH nitroreductase activity is absent in the cell metronidazole remains inactive.  Loss of the reductase activity can occur by nonsense or deletion mutations in rdxA (Debets-Ossenkopp et al., 1999; Goodwin et al., 1998; Tankovic et al., 2000).  In addition, NADPH nitroreductase activity can be severely reduced by a single missense mutation (a single amino acid change), which reduces its ability to activate metronidazole (Paul et al., 2001).  All these mutations result in loss of the enzyme activity necessary for the drug to be effective in the cell, hence the cell becomes resistant to metronidazole.  But, loss of enzymatic activity does not provide a genetic example of how that enzyme originally “evolved.”  Hence, mutations that provide resistance to metronidazole cannot be offered as true examples of “evolution in a Petri dish.”

Figure 2.  Activation of the antimicrobial agent, metronidazole.
After being transported into the cell, metronidazole requires structural modification to obtain its active, antimicrobial form.  This activation is achieved by the enzyme, NADPH nitroreductase, which is a product of the rdxA gene. Mutations in rdxA can prevent synthesis of a functional NADPH nitroreductase activity, which prevents metronidazole from becoming activated.

Several bacteria, including Escherichia coli, construct a mulitiple-antibiotic-resistance (MAR) efflux pump that provides the bacterium with resistance to multiple types of antibiotics, including erythromycin, tetracycline, ampicillin, and nalidixic acid.  This pump expels the antibiotic from the cell’s cytoplasm, helping to maintain the intracellular levels below a lethal concentration (Grkovic et al., 2002; Okusu et al., 1996) (Figure 3).  The MAR pump is composed of the proteins MarA and MarB, whose synthesis is inhibited by the regulatory protein, MarR (Alekshun and Levy, 1999; Poole, 2000) (Figure 3). 
Mutations that reduce or eliminate the repression control of MarR result in over-production of the MarAB efflux pump, which enables the cell to expel higher concentrations of antibiotics or other antibacterial agents (Oethinger et al., 1998; Poole, 2000; Zarantonelli et al., 1999).

Figure 3.  Multidrug resistance efflux pump.
(A)Antibiotic sensitive bacterium.  The antibiotics enter the cell through various portals, including the OmpF porin.  Expression of the marR gene produces the regulatory protein, MarR.  This protein binds to the promoter (labeled as P) of the multidrug resistant operon, inhibiting expression of genes marA and marB.  (B) Antibiotic resistant bacterium.  A mutation of marR that reduces the activity of MarR enables the promoter to function constitutively.  Both marA and marB are now expressed.  These two proteins form an efflux pump, which transports antibiotic molecules out of the cell’s cytoplasm.  MarA also binds to the promoter (labeled as P) and increases the transcription rate of the operon, which increases production of both MarA and MarB. In addition, production of MarA indirectly reduces the synthesis of the OmpF porin, thereby reducing the number of these porins in the membrane.  The combination of fewer porins for transport of an antibiotic into the cell, and the increased number of MarAB efflux pumps removing the antibiotic out of the cell, provides the bacterium an increased tolerance to several antibiotics.

 

The protein MarA also acts as a positive regulator by stimulating increased production of both MarA and MarB proteins (Alekshun and Levy, 1999) (Figure 3).  In addition, the MarA protein indirectly inhibits the production of the porin, OmpF, a channel in the membrane that allows entry of some antibiotics into the cell (Cohen et al., 1988). 
Therefore, increased expression of MarA increases the efflux of antibiotics out of the cell, and reduces the transport of some antibiotics into the cell (Figure 3).  Mutations of marR that reduce expression or activity of the MarR protein will thus enable over-expression of the MarAB efflux pump (Linde et al., 2000; Okusu et al., 1996), and provide an increased resistance of the bacterium to various antibiotics (Eaves et al., 2004; Hans-Jorg et al., 2000; Notka et al., 2002) (Figure 3).  MarR defective mutants also possess increased bacterial tolerance to some organic chemical agents, such as cyclohexane (Aono et al., 1998).

Mutations that increase production of this efflux pump enable these bacteria to survive exposure to various antibiotics.  As such, this is a beneficial mutation when the antibiotic is present in the environment. However, a mutation that causes loss of regulatory control (in this case the repressor protein, MarR) does not offer a genetic mechanism that can account for the origin of this regulatory control.

In other examples, resistance to erythromycin can also result from the loss of an 11 base pair segment of the 23S rRNA gene (Douthwaite et al., 1985), or a mutation that alters the confirmation of the 23S rRNA-reducing the affinity of the ribosome for the antibiotic (Gregory and Dahlberg, 1999; Vannuffel et al., 1992).  Chloramphenicol resistance was obtained by deletion of a 12 base pair region in domain II of the peptidyltransferase gene (Douthwaite, 1992).  Resistance to cephalosporins has been linked to a dramatic alteration of membrane transport kinetics that is similar to porin-deficient strains (Chevalier et al., 1999).  Actinonin resistance in Staphylococcus aureus results from mutations that eliminate expression of the fmt gene (Margolis et al., 2000).  Zwittermicin A resistance in E. coli is associated with loss of proton motive force (Stabb and Handelsoman, 1998).  For Streptococcus gordonii, penicillin tolerance may involve loss of regulatory control of the arc operon (Caldelari et al., 2000).  And, E. coli can survive the presence of ß-lactams, such as ampicillin, by halting cell division, making the cell less sensitive to the lethal affect of the antibiotic (Miller et al., 2004).

 

These resistance mutations described above cause the loss of a pre-existing biological system, including cell division and proton motive force.  Even though antibiotic survival is a “beneficial” phenotype, these mutations fail to provide a genetic example of how each of these systems originated.  As such, they fail to provide a genetic means to fulfill the predictions of “descent with modification.”

 

Resistance to other antibiotics, such as kanamycin, can result from loss or reduction of synthesis of a transport protein (OppA) (Kashiwagi et al., 1998).  Ciprofloxacin and imipenem resistance can result, at least in part, from the decreased formation of the outer membrane porin, OmpF (Armand-Lefèvre et al., 2003; Hooper et al., 1987; Yigit et al., 2002).  An increase in meropenem and cefepime resistance is also associated with loss of OmpF, and another porin, OmpC (Yigit et al., 2002).  And, Enterobacter aerogenes can become resistant to various antibiotics when a mutation dramatically reduces the conductance of a membrane porin (Dé et al., 2001).

 

Each of these resistances described in the previous paragraph result from the reduction or loss of a transport system.  However, genetic mechanisms necessary for evolution would need to account for the origin of these various transport systems.  Thus, these antibiotic resistance mutations do not provide the necessary genetic changes for “common descent.”  Rather, they are genetically inconsistent with the requirements of evolution, each involving the loss of a pre-existing transport activity.

 

As a group, the mutations associated with antibiotic resistance involve the loss or reduction of a pre-existing cellular function/activity, i.e., the target molecule lost an affinity for the antibiotic, the antibiotic transport system was reduced or eliminated, a regulatory system or enzyme activity was reduced or eliminated, etc.(Table I).  These are not mutations that can account for the origin of those cellular systems and activities.  While these mutations would certainly be “beneficial” for bacterial survival when an antibiotic is present in the environment, this benefit is at the expense of a previously existing function.  This is analogous to removing an interior wall of a house to make a larger dining room.  While this larger dining room may be desirable (i.e., beneficial), the mechanism of removing this wall cannot legitimately be offered as an example of how this interior wall was originally built.  Hence, the survival benefit of a mutation is only a portion of the genetic characteristics necessary for mutations to achieve “evolution in a Petri dish.”  Such mutations must also provide the genetic basis for common “descent with modification.” 
While this directly contradicts the claims made by many proponents of evolution, the molecular data for antibiotic resistance are very clear.

 

These mutations also cannot provide a mechanism that continues to “evolve” the level of protein specificity or protein activity that is necessary for normal cellular function.  While such mutations are excellent examples of bacterial adaptation, they are actually the antithesis of the mutational change necessary for evolution.  Yet, these are the very examples evolutionists offer as verifiable demonstrations of “evolutionary change.”  Ironically, these mutations are, in fact, verifiable examples of a creation model—initial complexity being mutated to a level of greater simplicity.

The spontaneous acquisition of antibiotic resistance is often referred to as “gaining” resistance, but it is more appropriately identified as a loss of sensitivity.  Thus, antibiotic resistance results from the loss of pre-existing systems in the bacterial cell. 
Such changes clearly provide no genetic mechanism for the origin of such cellular features as enzyme specificity, transport activity, regulatory activity, or protein binding affinity.  Yet, evolutionists consistently claim that mutations do provide a genetic mechanism for the origin of biological activity and common “descent with modification,” and consistently offer the types of mutations described above as examples.

 

Fitness Cost of Antibiotic Resistance

While mutations that provide resistance to an antibiotic can be considered “beneficial,” they often come with a physiological cost (Andersson and Levin, 1999; Maisnier-Patin et al., 2002).  In fact, Björkman et al. (2000) conclude that most types of antibiotic resistance will impart some biological cost to the organism.  For example, rifampin resistance in Mycobacterium tuberculosis (Billington et al., 1999), E. coli (Reynolds, 2000), and Staphylococcus aureus (Wichelhaus et al., 2002) resulted from mutations to the RNA polymerase that also reduced the relative fitness of most of the mutant strains.  Although the biological cost reported by these researchers was generally not severe, it was measurable.

Mutations resulting in clarithromycin resistance in Helicobacter pylori reduce the relative fitness of the organism (Björkholm et al., 2001).  Resistance to high levels of fluroquinolone by Salmonella enterica involves mutations that impart a high fitness cost to the organism (Giraud et al., 2003).  And, fusA mutations that provide fusidic acid resistance to Staphylococcus sp. impose a significant loss of “relative fitness” (Gustafsson et al. 2003; MacVanin et al., 2000).  Resistance to actinonin by S. aureus also accompanies a dramatic loss of “fitness” resulting in significant growth impairment (Margolis et al., 2000).  E. coli resistance to streptomycin may dramatically reduce the rate of protein biosynthesis (Zengel et al., 1977).  And, some bacteria suspend cell division to minimize their sensitivity to ampicillin (Miller et al., 2004), which clearly reduces the overall fitness of the organism.

 

This cost of “relative fitness” appears to vary considerably depending on both the organism and the antibiotic. Many of the resistant mutants that have been studied, however, including some of those mentioned above, can subsequently eliminate some or much of the fitness cost by reversion or suppression mutations, which also stabilizes the mutation (Andersson and Levin, 1999; Lenski, 1998; Massey et al.,  2001).  The degree that a reversion mutation restores fitness probably depends on the location of the mutation and whether a single mutation is able to restore some or all of the wild-type “fitness.

Clearly the fitness of some mutant strains is permanently reduced (sometimes dramatically), and evolutionists have typically  ignored such affects in their rush to promote antibiotic resistance as “evolution in the Petri dish.”  In fact, they often test relative fitness of these mutants under very narrow cultivation parameters, which minimizes the detectable loss of fitness for a given mutation. On the other hand, the fitness loss of some mutants is negligible (esp. following reversion mutations).  So, the effect of spontaneous resistance on bacterial fitness appears to vary from mutant to mutant. .. Resistant mutations do impose a biological cost, though, in the loss of pre-existing biological systems and activities.  Such biological cost is not compensated by reversion or suppression mutations.  Even though such mutations may not always result in detectable levels of reduced “fitness,” they stand as the antithesis of common “descent with modification.”

 

Summary

Resistance to antibiotics and other antimicrobials is often claimed to be a clear demonstration of “evolution in a Petri dish.”  However, analysis of the genetic events causing this resistance reveals that they are not consistent with the genetic events necessary for evolution (defined as common “descent with modification”).  Rather, resistance resulting from horizontal gene transfer merely provides a mechanism for transferring pre-existing resistance genes.  Horizontal transfer does not provide a mechanism for the origin of those genes.  Spontaneous mutation does provide a potential genetic mechanism for the origin of these genes, but such an origin has never been demonstrated.  Instead, all known examples of antibiotic resistance via mutation are inconsistent with the genetic requirements of evolution.  These mutations result in the loss of pre-existing cellular systems/activities, such as porins and other transport systems, regulatory systems, enzyme activity, and protein binding.  Antibiotic resistance may also impart some decrease of “relative fitness” (severe in a few cases), although for many mutants this is compensated by reversion.  The real biological cost, though, is loss of pre-existing systems and activities.  Such losses are never compensated, unless resistance is lost, and cannot validly be offered as examples of true evolutionary change.

(Kevin Anderson, Ph.D. © 2005;Is Bacterial Resistance to Antibiotics an Appropriate Example of Evolutionary Change?)

 

This statement paralleled such changes well:

"[bacteria] will destroy their own bridges to prevent an enemy crossing (or even better, right when the enemy is crossing), sabotage their own factories if the enemy is using them to churn out armaments, or burn their own crops so the enemy will run out of food."(Jonathan Sarfati, The Greatest Hoax on Earth? (Creation Book Publishers: Atlanta Georgia, 2010), p. 52.)