We use antibiotics to destroy the bacteria.
Over the last century, we were able to exploit the potential of antibiotics for our benefits such as treating infections, increasing agricultural yield, etc. We evoked the mass production of antibiotics by microbial fermentation or chemical synthesis with amplified dose and potency.
However, the interesting fact is that antibiotics is been naturally produced by bacteria and fungi for millions of years as secondary metabolites at a concentration much lower than the therapeutic dose.
But why the microbes are producing antibiotics if it is meant to destroy them? And what are antibiotics used for, by the microbes that produce them?
Why microbes produce antibiotics?
Antibiotics as a survival weapon
Let’s have a close look at bacteria living in the soil habitat.
Bacteria live in the soil. Most of the time soil provides them with enough warmth, temperature, and other necessary conditions for their survival. Bacteria get enough food and oxygen. In short, bacteria adore the environment provided by the soil and thrive.
However, if we zoom in to the bacterial environment, they are not very happy. All the nutrients in the soil are not only for itself. It must be shared with?neighbors?including other species of bacteria, fungi, etc.
Furthermore, the limiting nutrients and incapability of bacteria to take up enough nutrients add more misery to the life of bacteria.
What might look perfect from distance is a battleground for survival, with continuous competition for nutrients.
This is the scenario for other bacteria living in other habitats, be it in the ocean, hot springs, sewage, inside the human gut, etc.
In the natural habitat, diverse microbial communities coexist and must continuously combat the constant environmental threat and selective pressure.
Survival is the major challenge since nutrients are deficit.
To survive in the environment and to compete with other bacteria, they need a lead over the other. And evolution favored the bacteria by giving that lead: Antibiotics.
Therefore, classically thinking, bacteria produce antibiotics for the same reason we use antibiotics: to kill other bacteria and thereby reducing the competition for nutrients.
Antibiotics are chemicals produced by the microbes that can inhibit the growth or can kill the bacteria.
- Rapamycin is an antimicrobial compound produced by the soil bacteria Streptomyces?hygroscopicus. It acts as an anti-fungal compound against a variety of soil fungi giving the Streptomyces a competitive advantage over the fungi in soil.
- Phenazine is an antibiotic produced by the bacteria Pseudomonas fluorescens (a bacteria colonizing the rhizosphere of wheat) to inhibit the growth of the fungal pathogen, Gaeumannomyces graminis var. tritici, thereby suppressing the root and crown disease of barley.
- Some fungus-growing ants carry antibiotic-producing actinomycetes on their cuticle for the biocontrol of the fungal garden parasite.
Antibiotics as a signaling molecule
Having said that, many scientists have begun to wonder whether this is the complete portrait because the antibiotic concentrations in natural habitats are too low to inhibit the growth or kill other bacteria.
As it happens, bacteria could respond to low or sub-MIC levels of antibiotics in a great variety of other ways such as in the control of transcription and translation, expression of virulent genes, quorum sensing, etc.
(sub-MIC concentration of antibiotics is defined as the concentration of an antibiotic that does not kill bacteria or affect bacterial growth but is still active in altering bacterial biochemistry.)
Chemical communication is a crucial attribute in the diverse microbial population, helping the microbes coordinate with each other in an organized fashion.
This has led to the assumption that microbes produce antibiotics to interact with other microbes and antibiotics could function as signals between cells.
Many antibiotics at such a low concentration have many biological activities such as effecting the transcription, expression of virulent genes, etc other than their inhibitory role.
Signaling Transcriptional activation
It has been postulated that the lower level of antibiotic concentrations attribute to modulate the transcriptional profile of target bacteria, implying the fact that the antibiotics are?signaling?molecules, with the potential to kill bacteria when applied at unnaturally high concentrations.
And these antibiotic molecules play a crucial part in the dynamics of microbial communities, thereby contributing to both competitive and interactive responses.
Thus, antibiotics perform a dose-dependent dual role, inhibition at high concentrations, and transcriptional changes at low concentrations.
- Thiostrepton, antibiotic produced by several strains of streptomycetes, inhibits the protein synthesis by binding 23S rRNA, which could act as a transcription inducer at a concentration lower than the inhibitory concentration.
- Puromycin, anaminonucleoside antibiotic, from the Streptomyces alboniger bacterium affects nucleic acid synthesis, mediated by its aminonucleoside moiety, despite having a chain termination activity in polypeptide synthesis.
Sub-MICs of antibiotics can, therefore, induce extensive transcriptional changes in bacteria.
However, another research study emphasizes the fact that although antibiotics act as?signaling?molecules and their production is social, it is not cooperative.
The research team studied 13 strains of Streptomyces bacteria from a soil sample and analyzed each strain’s capability to inhibit every other strain. And when the third strain of bacteria was added to every pair of bacteria, it affected the original interaction between the previous two bacteria. Bacteria were able to increase their antibiotic production and could inhibit the growth of strains they couldn’t before. Also, bacteria were able to suppress antibiotic production in competitors.
The authors postulated that this kind of bacterial interaction is precisely competitive rather than cooperative backing the use of antibiotics as weapons.
Signaling the expression of virulent genes
Virulence is defined as the ability of the microorganisms to cause disease and the genes encode virulent factors are called virulent genes.
Some antibiotics, at concentrations below the sub-MIC, can modulate the expression of certain virulent genes.
- Sub inhibitory concentration of several antibiotics including, metronidazole, vancomycin, and clindamycin could induce the major virulence factors encoding genes of bacteria Clostridium difficile, a nosocomial pathogen responsible for diarrhea.
- On the contrary, the sub-MIC level of the antibiotic azithromycin could mount an exactly converse event such as suppression of the alginate overproduction and biofilm formation in the bacteria Pseudomonas aeuroginosa.
These contrary remarks indicate that the role of antibiotic molecules differs greatly while functioning as a signaling molecule.
The antibiotic-producing microbes produce antibiotics for specific purposes. Antibiotics are equipped with various activities and roles in the diverse microbial community. The most important among them are,
- Antibiotic acting as signaling molecules for various biochemical and physiological reactions in the bacterial cell.
- Antibiotic acting as a growth inhibitory molecule.