Development and Stability of Antibiotic Resistance

Antibiotic resistance is of current concern. Bacteria have grown to be increasingly resistant to popular antibiotics and we’re facing an increasing resistance problem. The current thesis was targeted at studying the impact of antibiotic treatment on pathogenic bacteria in addition to on the standard human microbiota, with concentrate on resistance development. One of the facets that affect the look of acquired antibiotic resistance, the mutation frequency and biological cost of resistance are of special importance. Our work suggests that the mutation frequency in clinical isolates of Helicobacter pylori was broadly speaking greater than for other studied bacteria such as for example Enterobacteriaceae; ¼ of the isolates displayed a mutation frequency greater than Enterobacteriaceae defective mismatch repair mutants and may be thought to be mutator strains. In H. pylori, clarithromycin resistance confers a biological cost, as measured by decreased competitive ability of the resistant mutants in mice. In clinical isolates, this cost might be paid down, in line with compensatory evolution stabilizing the current presence of the resistant phenotype in the populace. Hence, compensation is really a clinically relevant phenomenon that may occur in vivo…

Moreover, our results show that clinical utilization of antibiotics selects for stable resistance in the human microbiota. This is essential for all reasons. First, many commensals sporadically may cause severe illness, although they have been the main normal microbiota. Therefore, stably resistant populations boost the threat of unsuccessful treatment of such infections. 2nd, resistance in the standard microbiota may donate to increased resistance development among pathogens by interspecies transfer of resistant determinants….

Contents: Antibiotic Resistance Development and Stability

The Antibiotic Resistance Problem
THE INTRODUCTION OF ANTIBIOTICS
Mechanisms of Action of Antibiotics
ANTIBIOTIC RESISTANCE
Mechanisms of Antibiotic Resistance
Acquired Antibiotic Resistance
SELECTION OF ANTIBIOTIC RESISTANT BACTERIA
The Volume of Drug Use
The Rate of Formation of Resistant Mutants
Transmission of Resistant Bacteria
STABILITY OF ANTIBIOTIC RESISTANT BACTERIA
The Biological Cost of Antibiotic Resistance
Compensatory Evolution
FURTHER FACTORS INFLUENCING THE STABILITY OF ANTIBIOTIC RESISTANCE
Genetic Linkage of Resistance Genes
No-cost Associated Resistance Mutations
THE ROLE OF THE HUMAN NORMAL MICROBIOTA IN ANTIBIOTIC RESISTANCE DEVELOPMEN
The Human Microbiota
GENERAL AIM
SPECIFIC AIMS
MATERIALS AND METHODS
Bacterial Species Studied in the Present Thesis
Helicobacter pylori
Enterococcus spp
Staphylococcus epidermidis
Į-streptococci
Escherichia coli
Bacterial Strains (I-IV)
DNA Preparation and Polymerase Chain Reaction (I-IV)
Determination of Antibiotic Susceptibilities (II)
Minimal Inhibitory Concentration Determinations (MIC) (I-IV)
Mutation Frequency Determination (I, II)
Sequencing (II)
Statistical Analysis (II)
Mathematical Modelling (I)
Appendix 1
Appendix 2
In vivo Competition Model (I)
Pulsed-Field Gel Electrophoresis (PFGE) (IV)
Competition Assay on Human Skin (IV)
RESULTS AND DISCUSSION….