Home | | Essential Microbiology | Resistance to antibiotics

Chapter: Essential Microbiology: Antimicrobial Agents

Resistance to antibiotics

The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potentially crisis proportions.

Resistance to antibiotics

 

The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potentially crisis proportions.

As we have already suggested, the impact of certain antibiotics can be greatly reduced due to the development of resistance by target pathogens. This represents the greatest single challenge facing us in the fight against infectious diseases at the start of the 21st century. Fleming himself foresaw that the usefulness of penicillin might become limited if resistant forms of pathogens arose.

 

Not long after penicillin was put into general use, strains of Staphylococcus aureus were found which did not respond to treatment, and by 1950 penicillin-resistant S. aureus was a common cause of infections in hospitals. A decade later, a semi-synthetic form of peni-cillin, methicillin, was introduced; this was not affected by the β-lactamase enzymes that inactivated Penicillin G, and was used to treat resistant forms. Within years, however, came the first reports of strains of S. aureus that did not respond to methicillin. The incidence of methicillin-resistant S. aureus (MRSA) has increased greatly since, and it represents the major source of noso-comial infections. In 1980, synthetic fluoroquinoloneswere introduced to counter the threat of MRSA, but within a year 80 per cent of isolated strains had devel-oped resistance to these too. Vancomycin is regarded as a last-resort treatment forMRSA, for a number of reasons; it has a number of serious side-effects, its widespread use would encourage resistance against it, and it is extremely expensive.

A case of vancomycin-resistant Staphylococcus aureus (VRSA) emerged in Japan in 1996; a few months later it had reached the USA. This represents a serious threat; some of these strains respond to treatment with a cocktail of antibiotics, but already people have died from untreatable VRSA infections. In 2003, a strain of VRSA was shown to have obtained its vancomycin resistance by cross-species transfer from a strain of Enterococcus faecalis.

 

How does antibiotic resistance work?

 

We saw earlier how antibiotics exert their effects in a variety of ways, so it should come as no surprise that there is no single mechanism of resistance. Resistance may be natural, that is, intrinsic to the microorganism in question, or it may be acquired.

 

Some bacteria are able to resist antibiotic action by denying it entry to the cell; penicillin G for example is unable to penetrate the Gram negative cell wall. Others can pump the antibiotic back out of the cell before it has had a chance to act, by means of enzymes called translocases; this is fairly non-specific, leading to multiple drug resistance. Other bacteria are naturally resistant to a particular antibiotic because they lack the target for its action, for example, mycoplasma do not possess peptidoglycan, the target for penicillin’s action.

To avoid the action of an antibiotic, bacteria may be able to use or develop alter-native biochemical pathways, so that its effect is cancelled out. Many pathogens can secrete enzymes that modify or degrade antibiotics, causing them to lose their activ-ity; we have already seen that penicillins can be inactivated by enzymatic cleavage of their β-lactam ring. Similarly, chloramphenicol can be acetylated, while members of the aminoglycoside family can be acetylated, adenylated or phosphorylated, all leading to loss of antimicrobial activity.

 

Mutations may occur which modify bacterial proteins in such a way that they are not affected by antimicrobial agents. You will recall that streptomycin normally acts by binding to part of the 30S subunit on the bacterial ribosome; the actual binding site is a protein called S12. Mutant forms of the S12 gene can lead to a product which still functions in protein synthesis, but loses its ability to bind to streptomycin. Similarly, mutations in transpeptidase genes in staphylococci means they do not bind to penicillin any more, so cross-linking of the cell wall is not inhibited.

 

How does resistance arise?

Occasionally, mutations occur spontaneously in bacteria, which render them resistant to one antibiotic or another. Usually the mutation leads to a change in a receptor or binding site such as those just described, rendering the antibiotic ineffective. The changes are usually brought about by point mutations occurring at very low frequency on chromosomal DNA. Bacteria can, however, become resistant much more rapidly by acquiring the mutant resistance-causing gene from another bacterium. This is called transmissable antibiotic resistance; it occurs mainly as a result of bacterial conjugation, and is the cause of most of the resistance problems we presently face. Transmissable resistance was first reported in Japan in the late 1950s, when multi-drug resistance in Shigella was shown to have been acquired by conjugation with resistant E. coli in a patient’s large intestine. E. coli is known to transfer R (resistance) plasmidsto several other gut bacteria including Klebsiella, Salmonella andEnterobacter, as well as Shigella. Whereas chromosomal mutations usually result in a modification to the drug’s binding site, genes carried on plasmids code for enzymes which inactivate it, (e.g. β-lactamases) or lead to its exclusion from the cell (translocases).

 

There is a strong link between the use of a particular antibiotic in a locality and the incidence of resistant bacterial strains. This is because of selective pressure favouring the resistant forms of a bacterium. Fortunately this can, at least in part, be reversed, as several studies have shown, where a more restricted use of certain antibiotics over several years was followed by a reduction in the incidence of resistant bacterial forms.

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Essential Microbiology: Antimicrobial Agents : Resistance to antibiotics |


Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.