Mechanisms and Genomics of Resistance



Important to know what is antimicrobial resistance?

 Antimicrobial resistance is the capacity of bacteria to survive exposure to a defined concentration of an antimicrobial substance. Antimicrobial resistance has multiple definitions according to the scientific discipline and the goals involved:

1. Clinical definition: the bacteria survive an adequate treatment with an antibiotic

2. Pharmacological definition: the bacteria survive a range of concentrations expressing the various amounts of an antibiotic present in the different compartments of the body when the antibiotic is administered at the recommended dose

3.  Microbiological and Molecular definition: the bacteria have a mechanism which governs a higher minimum inhibitory concentration (MIC) than the original or wild bacteria

4.  Epidemiological definition: any group of bacterial strains which can be distinguished from the normal (Gauss) distribution of MICs to an antibiotic.

Bacterial resistance to a particular antibiotic can be a natural property of the bacteria or a secondarily acquired mechanism. Surviving the effect of an antibiotic is a normal reaction of a bacterial cell. When successful, such a reaction gives origin to a clone of bacterial cells able to confront the antibiotic.

However, according to the mechanism of resistance, the bacterial clone may confront different amounts of antibiotic, ranging from a small amount, close to the amount formerly able to inhibit the growth (MIC) of the bacterial cell, to a very large quantity of antibiotics (e.g. hydrolysing exoenzyme produced by the bacteria). It is a very well known fact that bacteria can resist any antibiotic, and this is a global phenomenon which affects all countries.

However, characteristics of the resistance phenomenon relate to the affected bacterial species, the set of antibiotics involved, the distribution of the resistant strains in particular settings in which antibiotics are used (hospital, community, animal husbandry, etc.). The resistant strains are classified according to their identification (genus, species) and to their antibiotic resistance phenotype (sometimes referred to as antibiotype or resistance pattern).

The mechanism by which the bacteria are able to resist It is important to note that a bacterial cell often possesses more than one mechanism to resist to an antibiotic. Co-operation between several resistance mechanisms often generates high level resistance.

The genetic mechanism governing the proteins involved in the resistance and the origin of resistance two genetic mechanisms are involved, namely:

1. mutation in an existing gene (chromosome or plasmid), and

2. the de novo acquisition of a gene governing resistance. The location of the altered or the new genes is important (chromosomes, integrons, transposons or plasmids).

The most important consequence of the location of the resistance genes concerns the spread of the resistance:

–     a chromosomal mutation affects a bacterial cell. The clone issued from this cell will multiply and spread. This mode of spread is often called vertical transmission of resistance

–    a resistance gene located on a transposon or a plasmid can be transmitted horizontally, independently from the spread of the resistant clone.

Moreover, the horizontal transmission may occur between different bacterial species. Concomitantly or independently to the expansion of the resistant bacteria, plasmid (gene) epidemics can occur. Many of them have been reported affecting six to eight species of Gram-negative bacteria. Plasmids or transposons are the main systems (genetic material) transferring resistance from bacteria (donor) to bacteria (recipient). They usually carry more than one marker of resistance. Large plasmids may transfer several different mechanisms of resistance against a number of different antibiotics. Their concurrent appearance in the same bacteria explains that one antibiotic may continue to co-select for the whole set of resistance mechanisms (multi-drug resistance).


Antimicrobial resistance: an overview

J. Acar & B. Röstel  Rev. sci. tech. Off. int. Epiz., 2001, 20 (3), 797-810

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Professor Jonathan Iredell

Silent Catastrophy: Human Inpact on the Micrbiome and the Transmissible Gene Pool – ASM 2013 Adelaide

ASM2013 Iredell

 Making Sense of Resistant Genes – New Technology in defining Phenotypic and Molecular Methods in Detecting and Understanding Bacterail Resistance by John Merlino – Microbiology Australia

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Resistant Genes and New Technology



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