Antibiotic Resistance Mechanisms

A short overview

Red Queen Theory

Intrinsic Resistance​

Anti­bio­tic Resis­tance is not just a man-made pro­blem. On the con­tra­ry it is very well known, that bac­te­ria from natu­ral habi­tats con­tain dif­fe­rent defen­si­ve mecha­nisms to sur­vi­ve despi­te anti­bio­tic pre­sence. Reports from the pre-anti­bio­tic era (befo­re the dis­co­very of Peni­cil­lin by Fle­ming in 1928) are espe­ci­al­ly inte­res­t­ing regar­ding this so-cal­led intri­nisc resis­tance. That way, sci­en­tists did find some micro­bes being resistant to modern anti­bio­tics despi­te living 5000 years ago!

Howe­ver, to under­stand this phe­no­me­non it has to be taken into account that most anti­bio­tic pro­du­cers (even tho­se who are rele­vant for todays medi­ci­ne) are inha­bi­tants of soils. Hence, it seems quite con­sistant that non-pro­du­cers had to deve­lop a stra­tegy against anti­mi­cro­bi­als in order to sur­vi­ve next to anti­bio­tic pro­du­cing micro­or­ga­nisms. We’­re cal­ling this pro­cess of mutu­al ada­pa­ti­ons “Co-Evo­lu­ti­on”.

By the way, make sure you give “Ali­ce­’s Adven­tures in Won­der­land” a read! The included “Red Queen Theo­ry” is exact­ly describ­ing the phe­no­men of inter­ac­tions bet­ween two par­al­lel evol­ving orga­nisms. This is also com­pa­ra­ble to the simul­ta­nious evo­lu­ti­on and adjus­t­ments of prey and predator.

Antibiotic Resistance Mechanisms

Antibiotic Resistance Mechanism
Antibiotika Resistenz Mechanismen

The­re are tons of dif­fe­rent anti­bio­tics, but the­re are even more resis­tance mecha­nisms. Accor­ding to CARD (Com­pre­hen­si­ve Anti­bio­tic Resis­tance Data­ba­se) 2553 dif­fe­rent genes rela­ted to anti­bio­tic resis­tance (not coun­ting simi­lar genes in dif­fe­rent bac­te­ria) have been iden­ti­fied so far! Con­se­quent­ly, tho­se genes pro­vi­de all sort of defen­si­ve mecha­nisms against anti­bio­tics. Abo­ve all, the top 4 defen­si­ve stra­te­gies are: alte­ring the anti­bio­tic tar­get (1), alte­ring the anti­bio­tic (2), degra­de the anti­bio­tic (3) and efflux the toxic sub­s­tance (4). Nobo­dy can adapt bet­ter to a chan­ging envi­ron­ment than microorganisms! 

Global spread resistance

Global Spread​

Anti­bio­tic resistant micro­bes can be spread around the glo­be by seve­ral bio­lo­gi­cal and phy­si­cal forces. This con­ta­ins big metero­lo­gi­cal events (e.g. saha­ra-dust), ani­mal migra­ti­on, human tra­ve­ling, glo­bal wind- and water-streams and so on… Accor­ding to brand-new results (micro)plastic par­tic­les also are a poten­ti­al dri­ver for the spread of resistant bacteria!

Regar­ding humans, the big­gest thre­at is the well-known misu­se of anti­bio­tics. May it be fal­se indi­ca­ti­on, not taking the medi­ci­ne pro­per­ly, the use as a pre­cau­ti­on in agri­cul­tu­re, or water pol­lu­ti­on. As a result, humans are incre­asing the natu­ral pro­blem of anti­bio­tic resis­tance — espe­ci­al­ly in terms of spee­ding up the pro­cess of the evo­lu­ti­on of new resis­tance mechanisms.

Bacterial Conjugation or… how Bacteria have Sex

Let’s talk about sex baby! Bac­te­ri­al con­ju­ga­ti­on is giving bac­te­ria the pos­si­bi­li­ty to trans­fer any gene­tic infor­ma­ti­on from one to ano­ther — even bet­ween spe­ci­es! This of cour­se is an important fac­tor in the spread of anti­bio­tic resis­tance becau­se the sel­ec­ti­ve advan­ta­ge of anti­bio­tic resis­tance genes (ARGs) is huge and only micro­bes con­tai­ning ARGs will sur­vi­ve in an envi­ron­ment con­tai­ning anti­mi­cro­bi­al compounds. 

Howe­ver, con­ju­ga­ti­on is not the only way to spread such gene­tic mate­ri­al. Bac­te­ri­al repro­duc­tion fol­lows the rules of cell-divi­si­on which always leads to two iden­ti­cal cells that con­tain the exact same gene­tic infor­ma­ti­on — inclu­ding pos­si­ble anti­bio­tic resis­tance genes.

On that point — some food for thought: one cell gets resistant to any anti­bio­tic you can think of (through muta­ti­ons), divi­des into two cells every 30 minu­tes (like E. coli — a inha­bi­tant of our gut — does) and lives in a per­fect (microbial-)world with no death or nut­ri­ent limi­ta­ti­on. Within just one day, the­re would be ~3^14 resistant cells that could con­ju­ga­te with any other micro­be! As a num­ber 4 782 969… savor this slowly!

Howe­ver, it is not over yet as the­re is third way of how anti­bio­tic resis­tance genes can be spread. It is cal­led trans­duc­tion and invol­ves bac­te­rio­pha­ges (viru­s­es that infect bac­te­ria). Basi­cal­ly all that hap­pens is that the virus is taking gene­tic mate­ri­al from one cell, and injects it into ano­ther one during the pro­cess of infection.

Conjugation Antibiotic Resistance

Bacterial Conjugation or… how Bacteria have Sex

Let’s talk about sex baby! Bac­te­ri­al con­ju­ga­ti­on is giving bac­te­ria the pos­si­bi­li­ty to trans­fer any gene­tic infor­ma­ti­on from one to ano­ther — even bet­ween spe­ci­es! This of cour­se is an important fac­tor in the spread of anti­bio­tic resis­tance becau­se the sel­ec­ti­ve advan­ta­ge of anti­bio­tic resis­tance genes (ARGs) is huge and only micro­bes con­tai­ning ARGs will sur­vi­ve in an envi­ron­ment con­tai­ning anti­mi­cro­bi­al compounds. 

Howe­ver, con­ju­ga­ti­on is not the only way to spread such gene­tic mate­ri­al. Bac­te­ri­al repro­duc­tion fol­lows the rules of cell-divi­si­on which always leads to two iden­ti­cal cells that con­tain the exact same gene­tic infor­ma­ti­on — inclu­ding pos­si­ble anti­bio­tic resis­tance genes.

On that point — some food for thought: one cell gets resistant to any anti­bio­tic you can think of (through muta­ti­ons), divi­des into two cells every 30 minu­tes (like E. coli — a inha­bi­tant of our gut — does) and lives in a per­fect (microbial-)world with no death or nut­ri­ent limi­ta­ti­on. Within just one day, the­re would be ~3^14 resistant cells that could con­ju­ga­te with any other micro­be! As a num­ber 4 782 969… savor this slowly!

Howe­ver, it is not over yet as the­re is third way of how anti­bio­tic resis­tance genes can be spread. It is cal­led trans­duc­tion and invol­ves bac­te­rio­pha­ges (viru­s­es that infect bac­te­ria). Basi­cal­ly all that hap­pens is that the virus is taking gene­tic mate­ri­al from one cell, and injects it into ano­ther one during the pro­cess of infection.

Conjugation Antibiotic Resistance