Antimicrobial Awareness Week 2021: How resistance to antibiotics develops

Resistance is the ability of a bacterium to work against the antagonising effect of an antimicrobial agent, upon reproduction prevention or microbicidal (an agent that destroys microbes). 

The development of resistance to antimicrobial agents in microbes often develops as a result of unnecessary and inappropriate use of antimicrobials. 

Today, while the world is trying to develop new drugs, there are difficulties in treatment as a result of rapid development of resistance to these drugs.

The development of resistance to antimicrobial is a major public health problem all over the world.

The four types of resistance: 

1. Natural (intrinsic, structural) resistance

This kind of resistance is caused by the structural characteristics of microbes and it is not associated with the use of antimicrobials. It has no hereditary property.

It develops as a result of the natural resistance, or the microorganisms not including the structure of the target antimicrobial, or antimicrobial not reaching its target due to its characteristics. 

Gram negative bacteria vancomycin, for instance, does not pass in the outer membrane. So, gram-negative bacteria is naturally resistant to vancomycin. 

Similarly, L-form shape of bacteria which are cell wall-deficient forms of the bacteria, and the bacteria such as cell wall-less cell Mycoplasma and Ureaplasma are naturally resistant to beta-lactam antibiotics that inhibit the cell wall synthesis. 

2. Acquired resistance

As result of the changes in the genetic characteristics of microbes, an acquired resistance occurs because it is not being affected by the antimicrobial it has been responsive to before. 

This kind of resistance occurs mainly due to structures of chromosomes or extra chromosomals such as plasmid, transposon and others. 

3. Cross resistance

Some microorganisms are resistant to a certain drug that acts with the same or similar mechanism as some other drugs. 

This resistance is usually observed against antibiotics whose structures are similar —  resistance between erythromycin, neomycin-kanamycin or resistance between cephalosporins and penicillin. 

However, sometimes it can also be seen in completely unrelated drug groups. There is an example of cross-resistance between erythromycin-lincomycin. This may be chromosomal or extra-chromosomal origin. 

4. Multi-drug resistance and pan-resistance

Multidrug-resistant organisms are usually bacteria that have become resistant to the antibiotics used to treat them. This means that a particular drug is no longer able to kill or control the bacteria. 

Inappropriate use of antibiotics for therapy resulted in the selection of pathogenic bacteria resistant to multiple drugs. Multidrug resistance in bacteria can occur by either of the following mechanisms: 

1. These bacteria may accumulate multiple genes, each coding for resistance to a single drug. This type of resistance occurs typically on resistance plasmids. 
2. Resistance may also occur by the increased expression of genes that code for multidrug efflux pumps, enzymatic inactivation, changes in the structure of the target, among others.

Mechanism of resistance of antimicrobial

• Change in the target site: The changes that occur in the receptor connected to the drug and the region of the connection ‘Connection of the antibiotics’ target areas are different. They can be various enzymes and ribosomes. Resistance associated with alterations in the ribosomal target are the most frequently observed in macrolide antibiotics. Mutations in penicillin-binding proteins (beta-lactamase enzymes) and Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis and Enterococcus faecium strains can develop resistance to penicillin. 

• Enzymatic inactivation of antibiotics: Most gram-positive and gram-negative bacteria synthesise enzymes that degrade antibiotics. This enzymatic inactivation mechanism is one of the most important mechanisms of resistance. In this group, beta-lactamases, aminoglycosides, modifying enzymes (acetylase, fosforiase adenilaz and enzymes) degrade beta-lactam antibiotics and continually increase their number of which inactivates enzymes, include chloramphenicol and erythromycin. 

• Reduction of the inner and outer membrane permeability: This resistance is due to changes in the internal and external membrane permeability, decrease in drug uptake into the cell or quick ejection from the active resistance of the pump systems. As a result of a change in membrane permeability, decreased porin mutations in resistant strains can occur in proteins. 

• Flush out of the drug (active pump system): Resistance developing through the active pump systems is mostly common in the tetracycline group of antibiotics. Tetracyclines are thrown out with an energy-dependent active pumping system and cannot accumulate in the cell. Such resistance is in control of the plasmid and chromosomal. Active pumping systems are effective in resisting quinolones, 14-membered macrolides, streptogramins, chloramphenicol and beta-lactams.
• Using an alternative metabolic pathway: Unlike some of the changes in the target in bacteria, a new pathway for drug-susceptibility eliminates the need to develop an objective. Bacteria can gain the property of getting ready folate from the environment instead of synthesising folate.

Antibiotic resistance dissemination

Antimicrobial dissemination from food-producing animals to the surrounding environment takes place through either the excretion of antimicrobials through urine or faeces into surface waters and soils, or the application of animal manure as fertiliser to soil or ponds. 

Untreated animal waste is used for a variety of purposes in subsistence economies. Intestines from poultry are also used as feed for aquaculture, leading to higher levels of resistance in Enterococcus spp. isolates in fish intestines.

Antibiotics are extensively used both on human and animal health practices in developed and developing countries of the world, mainly for treatment and control of various diseases.

However, the use, misuse and overuse of these medicines contributed to favourable conditions for the emergence, occurrence and development of antibiotic resistant bacteria. 

Views expressed are the author’s own and don’t necessarily reflect those of Down To Earth.

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