Bacterial Shield against the antibiotics

February 13, 2017

The bacterial pathogens were known from a long period of time to be a cause of several types of infection, from mild skin irritation to life-threatening sepsis resulting in sudden and unexpected death. The medicine of curing the infections was changed by the groundbreaking discovery in 1928 of Scottish biologist Alexander Fleming, penicillin, first known antibiotic. The development of new compounds of antibiotics skyrocket from that moment reaching more than a 100 substances, however since 1987 not a new class of antibiotic was discovered. The belief from late 70’s, that we can treat all the bacterial infections, over-prescription of antibiotics for humans and in animal agriculture and lack of discoveries of new drug types, put us as a humanity in the stalemate situation. It is predicted that in 2050 every minute someone will die, because of the bacterial resistance of antibiotics according to the World Health Organisation. That’s why the wide range of basic research is right now important to find alternatives to antibiotics and treatment.

Bacteria compared to mammalian cells are way smaller organisms. Their cells are well equipped with several mechanisms of virulence to affect the host cells for better survival and growth and also to protect themselves from environmental conditions, for example, in the presence of antibiotics. To understand why bacteria become really hard to fight back an opponent in infection diseases, the identification of the molecular mechanisms and strategies used by pathogens to avoid the impact of antibiotics is required. This short article is dedicated to the bacterial mechanisms of resistance to antibiotics.

First of all, it should be highlighted that usually if a bacteria is resistant to one of the members of the particular class of the antibiotics, it will show resistance to most, if not all substances from the same class.

Bacterial pathogens can modify the antibiotic itself to affect its chemical properties and avoid the consequences of particular antibiotic that entered the bacterial cell. The hydrolysis is one of the major processes involved in the antibiotic resistance, described from the beginning of an antibiotic era. In the literature, more than few thousands of hydrolysing enzymes were characterized, as an example is β-lactamase responsible for degradation of the antibiotics like penicillin or carbapenems. Those enzymes are found in bacteria, as follows: Klebsiella pneumoniae, Pseudomonas aeruginosa or Escherichia coli. Another way of modifying the antibiotics by bacteria is the addition of the chemical group, affecting the sphericity of the molecule, leading to the inhibition of the binding of the target of the antibiotic.

One of the mechanisms used, especially by Gram-negative bacteria, which are less permeable than Gram-positive, is to reduce mentioned permeability of the outer membrane. This strategy is found in the several bacterial families of Enterobacteriaceae, Pseudomonas species. and Acinetobacter species and reduce the entry of the antibiotics to the bacterial cells. This is achieved by reduction of non-selective porins (a barrel shape proteins, used as a channel across the membranes of the cells), exchange them with more specific channels and decrease in the antibiotic entrance in the bacterial cells.

Another strategy found in Gram-negative bacteria is an increase in activity of efflux pumps that remove the drugs from the bacterial cells. The efflux pumps are the main contributor to the antibiotic resistance of pathogens. In bacteria, there are found two types of efflux pumps, characteristic for specific substrate – antibiotic or with a wide range of substrates, multidrug resistance efflux pumps. Those efflux pumps were discovered in several bacterial species, for example, K. pneumoniae, Staphylococcus aureus or Streptococcus mutans.

A different strategy is to mutate the target under the pressure of the environment, in this case, the presence of antibiotics, to avoid the consequences of the antibiotic effect. A great example is S. aureus and resistance on the linezolid, a drug targeting 23S rRNA ribosomal subunit in Gram-positive bacteria. However, the antibiotic pushed the selection of the bacteria containing the mutation of the 23S rRNA ribosomal subunit, affecting the fitting of the drug in the target protein and leading to resistance of S. aureus.

Other commonly known way of applying the mutation in the genome by bacteria is a transformation process, an uptake of DNA molecule from the environment, that could consist genes of resistance. For example, a Streptococcus pneumoniae acquired penicillin-resistant genes from closely related S. mitis by recombination.

From those few examples of the most common way of resistance mechanisms found in bacteria, we can conclude that nature prepared the microorganisms in well-designed weapons against the possible changes in the environment, promoting the survival of the most adapted, in this case, most antibiotic resistant. That also brings a need for development other strategies of fighting back the infections in the future not only focusing on the bacteria as a target but boosting the host responses and immune system.