Bacterial Resistance

Bacterial resistance mechanisms

1.Resistance mechanisms to antibiotics
Resistance to antibiotics may result from innate (intrinsic) or acquired mechanisms.
Intrinsic resistance is a trait of a bacterial species. For example, the target of the
antimicrobial agent may be absent in that species, the cell envelope (cell membranes and
peptidoglycan) may have poor permeability for certain types of molecules or the bacterial
species may produce enzymes that destroy the antimicrobial agent. These bacteria are
clinically resistant, but should more accurately be referred to as “unsusceptible”, as it is
often merely a matter of increasing the concentrations of the antimicrobial agent to
levels that may never be reached during therapy, or only at certain sites.
A bacterial strain can acquire resistance either by mutation or by the uptake of
exogenous genes by horizontal transfer from other bacterial strains. Genes encoding
enzymes that can modify the structure of an antimicrobial are commonly transferable
(penicillinases and cephalosporinases (bla-genes), acetyl transferases modifying e.g.
aminoglycosides (aac-genes), as are genes leading to target modification (erm-genes),
methicillin-resistance (mecA-genes) and glycopeptide-resistance (van-genes). There are
several mechanisms for horizontal gene transfer, mainly based on mobile genetic
elements, which often function in concert (Dobrindt 2004). Large plasmids with many
different genes can be transferred from bacterium to bacterium by conjugation.
Transposons can carry several resistance genes. They cannot replicate by themselves,
but can move within the genome, e.g. from plasmid to plasmid or from chromosome to
plasmid. Integrons can also encode several resistance genes. They cannot move by
themselves, but encode mechanisms both to capture new genes and to excise and move
cassettes with genes within and from the integron. Integrons are commonly carried on
plasmids (EFSA, 2005), but may also be chromosomally-integrated such as in Salmonella
Typhimurium DT 104

2.Main bacterial mechanisms of antibiotic resistance

Bacteria may resist antibiotic action by using several mechanisms. Some bacterial
species are innately resistant to one class of antibiotics, e.g. bacteria are resistant due to
their intrinsic envelope that limits the antibiotic penetration or to the presence of a low
level of efflux systems that decrease intracellular antibiotic concentration (Nikaido, 2003;
Li and Nikaido, 2004). In such cases, all strains of that bacterial species are likewise
resistant to all the members of those antibacterial classes (see Definition section
3.1.1.1).
An ongoing and increasing concern is bacteria that become resistant: e.g. initially
susceptible bacteria become resistant to antibiotics and consequently disseminate under
the selective pressure of use of these antibiotics (which kill other competitive bacteria).
Several mechanisms of antimicrobial resistance are readily spread to a variety of
bacterial genera.
A simple technical definition of the various resistance mechanisms may be proposed for
classification: mechanical barrier (altering the required intracellular dose of antibiotic);
enzymatic barrier (expression of a detoxifying enzyme that modifymodifies the
antibiotic); target protection barrier (mutation or expression of a molecule impairing the
antibiotic recognition and activity)
3.Bacterial biofilms and resistance
In practice, most bacteria are associated with surfaces and grow as biofilm rather than as
planktonic cells. Bacterial biofilms have been consistently described as being more
resistant to biocides and antibiotics than planktonic cells (Bisset et al. 2006, Gilbert et al.
2003, Maira-Litrán et al. 2000, Smith and Hunter 2008). The reasons for this decrease in
susceptibility is a biofilm-associated phenotype (Ashby et al. 1994, Brown and Gilbert
1993, Das et al. 1998), including decreased metabolism, quiescence, reduced
penetration due to the extracellular polymeric matrix (Pan et al. 2006), enzymatic
inactivation of biocides (Giwercman et al. 1991, Huang et al. 1995, Sondossi et al.
1985), and the induction of multi-drug resistant operons and efflux pumps (Maira-Litrán
et al. 2000).
Although bacteria within biofilms are undeniably more resistant to biocides and
antibiotics, the link between the uses of biocides against bacterial biofilm and potential
emerging antibiotic resistance is not straightforward. In a recent study investigating the
use of chloraminated drinking water against Ps. aeruginosa biofilm, there was no
evidence that the use of chloramine induced an increase in antibiotic resistance (Jurgens
et al. 2008).
Reference:
 Anderson GG, O'Toole GA. Innate and induced resistance mechanisms of bacterial
biofilms. Curr Top Microbiol Immunol 2008; 322:85-105
 https://ec.europa.eu/health/scientific_committees/opinions_layman/triclosan/en/glossary/
abc/bacterial-resistance.htm (Identified at 9 p.m.)