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Chromosomal mutation and recombination

In this article we will learn how antibiotic resistant mutants arise and are selected _in vivo_
© Wellcome Genome Campus Advanced Courses and Scientific Conferences

Bacterial clonal reproduction

Bacterial cells reproduce clonally. During clonal reproduction, each bacterial progenitor cell copies its DNA at high fidelity before splitting into two new cells (progeny), each with a single copy of the genome. Random errors in DNA replication can occur during this process, resulting in a clonal progeny that will inherit replication “errors” in their DNA. These errors are known as mutations.

Selection of antibiotic resistant mutants

Mutations are rare but because bacterial cell populations multiply exponentially, a subset of mutant cells may be present in the population. Just by chance, some of these mutant cells can be resistant to antibiotics, for example, if mutations alter the antibiotic target (or through other mechanisms described in step 1.16). In the absence of antibiotics the mutant cells will only ever exist as a tiny proportion of the total population, roughly 1 in a billion cells (Figure 1A). In the presence of antibiotics, all bacterial cells except for the antibiotic-resistant mutants will be killed (Figure 1B). In this context, antibiotic-resistant mutations confer an adaptive advantage and antibiotic-resistant cells are able to grow and multiply. Over time, the new bacterial population will be made up of mostly (or entirely) antibiotic-resistant mutant cells (Figure 1C).

Figure1.17.1Figure 1. A: Population of bacteria, with a highlighted individual carrying a mutation; B: Antibiotic kills all the sensitive bacteria, indicated by a skull and crossbones. The highlighted individual from A is resistant. C: population of resistant bacteria unaffected by antibiotic

Resistance through mutations in chromosomal DNA is the main driver of acquired resistance in certain bacterial species, such as Mycobacterium tuberculosis and Helicobacter pylori, or for particular antibiotics, especially synthetic agents such as fluoroquinolones and oxazolidinones.

Antibiotic-resistant mutations can be transmitted “vertically” by clonal reproduction, as explained above, but also “horizontally” via recombination.

Bacteria can exchange DNA using recombination mediated by mechanisms that include transduction (the transfer of DNA from one cell to another by bacteriophage), transformation (uptake of exogenous DNA from the surrounding environment) or conjugation (transfer of DNA from one bacterium to another via cell-to-cell contact). Some bacterial species, such as Helicobacter pylori, recombine quite frequently, whereas others, such as Mycobacterium tuberculosis, do not recombine.

Recombination can bring multiple genetic changes (mutations) all at the same time from the donor to the recipient. In conclusion, mutations acquired by bacteria are thus the result of vertically inherited mutations and horizontally acquired mutations via recombination.

© Wellcome Genome Campus Advanced Courses and Scientific Conferences
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Bacterial Genomes: Antimicrobial Resistance in Bacterial Pathogens

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