How to Use Phytochemicals as Antimicrobial Agents

These days, I read some papers about using phytochemicals as antimicrobial agents during the isolation period after my furlough(I'm currently doing my duty in ROKAF). So, I've read some paper about it('cuz I was so bored that I almost died lol) and I found out that antibiotic resistant bacteria can affect hugely in our lives. Compared to the past, frequency of there emergence is sky rocketing and soon, I guess, there won't be any drugs to kill them. And I came up to an idea that 'Well, may be plants can solve this problem! They have been living on the ground with tons of bacteria that might kill them.' This is the reason why I read papers about it. I read "Synergistic interactions of phytochemicals with antimicrobial agents: Potential strategy to counteract durg resistance", "The multi-faceted potential of plant derived metabolites as antimicrobial agents against multi drug resistant pathogens" and two more other papers(these two were not really nutritious, so it is nunecesary to write their title here). The point of these papers are how to enhance the ability of previous antibiotics. It's getting harder and harder to find new antibiotics. It's hard to find from actinomyces and hard to synthesize. This is not the end. You must go through tons of experiments to prove their ability as an antibiotics. This kind of methods takes so long. Therefore, there are some researchers who think just like me. 'Can't we just use previous antibiotics?' Well then, what kind of mechanism do we have to use? The papers that I said before showed me some concepts about it.

 

Before I start, we have to know how they have developed their resistance. If there are even just one individual tiny little fellow with resistance, it would survive. Then it will go to its friend and give its genes coding information for antibiotic resistant. As a result these two now have ability to resist from the antibiotics. So what kind of information is there and what do they do?

 

1) altering structures in the pencillin binding proteins(PBP; they catch antibiotics such as penicillin and don't let them in)

2) making more active cellular pumps(these pumps are called efflux pumps)

3) highering impermeability of the cell membrane by making the cell wall thinker or changing some components of their cell walls and membranes

4) generating enzymes which can degrade drugs such as β-lactamase.

 

There might be more mechanisms to let them survive, but the point of these mechanisms is it wouldn't let the concentration of antibiotics inside the cell high enough to kill them. They let them go out of the cell, degrade them and make them don't work or they just don't let them in. Well then how to solve these problems? It's right here.

 

1) There are some phytochemicals that depress PBP genes and PBP won't be found on their surface.

e.g. Corilagin, a tannin from Arctostaphylos uva-ursi extract showed effect to MRSA and reduced MIC(minimal inhibitory concentration)

2) Inhibiting enzymes which disturb antibiotics. If used antibiotics are degrade or modified, there functions usually get weaker or get lost. So it is important to inhibit the enzymes. This kind of enzymes are β-lactamase and chloramphenicol transacetylase which acetylates chloramphenicol and it binds to the ribosome poorly.

e.g. Augmentin: combination of amoxicillin with clavulanic acid(work as a β-lactamase inhibitor)

3) Phytochemicals to increase permeability and enhances efflux pumps can also make synergic effects with antibiotics. Mutated effluxes can decrease the drugs getting into the cell or can increase them getting out of the cell, which means the concentration of the drug inside the bacteria could be lower than the dose. Letting the drugs out can be also done by simple making this kind of pump more. Therefore, it is important to find efflux pump inhibitors(EPIs). But still we still don’t know about the mechanism of it.

e.g. MexAB-OprM pump: this extrudes a number of antibiotics to outside the bacteria including β-lactams, fluoroquinolones, tetracyclines, macrolides, novobiocin, chloramphenicol and co-trimexazole.

Also as I said previously, enhancing the permeability of the outer membrane of gram negative bacteria can increase the effect.

e.g. Epicatechin 3- gallate and caffeic acid: disintegrate the oily outer membrane of gram (–) bacteria which increase membrane permeability of hydrophobic antibiotics.

 

According to "The multi-faceted potential of plant derived metabolites as antimicrobial agents against multi drug resistant pathogens", I found some plant metabolites with antimicrobial properties. Well than, how does that property comes out? Usually their properties comes out from their structures.

1) The B rings of flavonoids: blocks the synthesis of bacterial DNA-> the B rings of them block the synthesis of the target bacteria. It forms hydrogen bonding between the ring and the bases used at forming DNA. There are myricetin, robinetin and epigallocatechin gallate

2) Binding with E. coli’s GyrB protein blocks its ATPase activity. It is also done by flavonoids such as quercetin

3) A peptide from Morrnga oleifera disrupt the membrane of E. coli, Salmonella typhimurum, P. aeruginosa and methicillin resistant S. aureus(MRSA).

To be shorten, flavonoids such as quercetin, kaempferol, apigenin, galangin, naringin derivatives reduce membrane fluidity of the bacterial cells and compromise the function of the cytoplasmic membrane. These kind of effects do not directly kill bacteria which mean they can be used as a bacteria static agent. So when they are used with antibiotics, they make synergic effects with them. However, we need more investigation about their mechanisms.