Inheritance of antibiotic resistance in bacteria
In resistance, antibiotics play a role of selection rather than a role. The widespread use of antibiotics leads to the rapid growth of resistant bacteria
Heredity is the maintenance of traits over many generations. The basis of heredity is chromosomes. Chromosomes of bacteria such as E. coli consists of 5x106 pairs of nucleotides divided into segments called genes, each of which determines the synthesis of a specific protein. Specific proteins such as enzymes and other cellular structures determine all the traits of an individual.
Chromosomes undergo replication before cell division. Thus each daughter cell receives an equivalent set of genes from the parent cell. Chromosome duplication is a precise process; however, each gene has a small probability of copying errors, thus giving rise to mutations. Mutation occurs randomly without external intervention with a very small frequency from 10-5 to 10-9.
Antibiotic-resistant bacteria are found everywhere, even in places where antibiotics have never been used. As soon as penicillin was invented in 1940, penicillin-resistant bacteria were reported. Today, the problem of drug resistance has become a leading concern in the treatment of infections and antibiograms are a daily test in microbiology laboratories.
The formation of drug resistance in microorganisms is due to genetic changes in the chromosomes or due to the reception of resistance plasmids.
Bacteria become resistant through 4 mechanisms: mutation, recombination, or harvesting of resistant plasmids or transposon harvesting.
Mutation to drug resistance
Many experiments have demonstrated that resistance arises due to mutations, such that resistance is related to genetic changes in chromosomes and can be passed on to future generations. The mutation occurs with a frequency of 10-5 - 10-9 .
In resistance, antibiotics play a role of selection rather than a role. The widespread use of antibiotics promotes the rapid development of drug-resistant bacteria by killing susceptible bacteria, allowing resistant bacteria to arise due to dominant mutations.
When a resistance mutation occurs in a bacterial population, the resistant bacterium can transfer the resistance gene to susceptible bacteria by one of three genetic transport mechanisms: transformation, transduction, and conjugation. depending on the species of bacteria. Recombination between two bacteria, each resistant to one antibiotic, gives rise to bacteria resistant to both antibiotics. In nature, resistance gene transport in transduction and conjugation occurs with a low frequency of about 10–5. In a transformer, the frequency is unknown but maybe even lower.
Harvesting resistant plasmids
The two resistance mechanisms above involve resistance genes located on chromosomes. Here drug resistance involves extrachromosomal plasmids. Resistant plasmids are transported by different mechanisms according to Gram-positive or Gram-negative bacteria.
Antibiotic-resistant plasmids in Gram-negative bacteria
In 1946, for the first time in Japan, people isolated many strains of Shigella resistant to many antibiotics: streptomycin, chloramphenicol, tetracycline, sulfonamides. The factor responsible for multidrug resistance is a drug-resistant plasmid called the R-factor. The typical R-factor is a large plasmid with two distinct, functional components. The first part of the RTF, called the resistance transfer factor, is about 80 kb and contains genes for self-replication and conjugation. The other is smaller, the R determinant, which is highly variable in size and contains the RTF and common resistance determinants that makeup one unit. The R factor often recombines to give rise to new combinations of drug resistance.
The R factor can not only be widely transmitted in many species of intestinal bacteria but also can be transmitted to many other bacteria such as cholera, plague bacteria...
The R-factor is transmitted in bacteria by contact, so drug resistance is widespread in a susceptible bacterial population as an infectious disease.
Antibiotic-resistant plasmids in Gram-positive bacteria
Resistance of many strains of Staphylococcus aureus to penicillin, erythromycin, and many antibiotics is also caused by plasmids. Plasmids in Gram-positive bacteria cannot be transported by conjugation but by phage-mediated transduction. Currently, most of the hospital-acquired penicillin-resistant staphylococci strains carry the penicillinase plasmid.
Transposons, also known as jumping genes, are small pieces of DNA containing one or more genes ending in identical but opposite nucleotide sequences (inverted repeat). can jump from plasmid to chromosome, or from chromosome to plasmid, or from plasmid to plasmid. All genes including resistance genes can be located on transposons. Transposons that direct heavy metal resistance, toxin formation, and the ability to utilize several metabolites (lactose, raffinose, histidine, sulfur compounds) have been described. Especially important in microbiology are antibiotic resistance transposons such as Tn3 carrying ampicillin resistance gene, Tn5 carrying kanamycin resistance gene, Tn10 carrying tetracycline resistance gene, Tn4 carrying resistance gene for ampicillin, streptomycin, and sulfamic antibiotics.