Please use this identifier to cite or link to this item: https://hdl.handle.net/1946/30377
Introduction: It is now becoming evident that pathogenic bacteria once again pose a serious threat to health worldwide as the number of antimicrobial-resistant bacteria continues to grow. Bacteria are living organisms that are able to adapt in order to be better fit to survive, this ability has allowed them to develop different mechanisms to withstand the actions of antibiotics. At least one mechanism of resistance is known against every class of antibiotics and many bacteria are resistant against a number of antibiotics. Bacteria can acquire resistance through modifications of the antimicrobial molecule, prevention to reach the antibiotic target, changes and/or bypass of target sites. The purpose of this study was to find out if there are areas of chemical property space related to a higher risk of resistance development and if the specific properties in these areas can be specified. Also if there is a difference in the properties of antibiotics that are prune to initiate resistance development in gram-positive as compared to gram-negative bacteria.
Methods: Available literature was reviewed in an attempt to gather information about some common antibiotics or families of antibiotics and bacteria that are known to be resistant to them. Principal component prediction (PCA-prediction) was subsequently performed on the antibiotics within ChemGPS-NP, a chemical global positioning system.
Results: A final set of 44 antibiotics where analyzed with ChemGPS-NP and visualized in three of the eight dimensions where the axes represent size, shape, polarizability (PC1), aromaticity and conjugation related properties (PC2) and lipophilicity including polarity and H-bond donor capacity (PC3). From this data four graphs were created, the first one representing the placement of the antibiotics in chemical space, in the second one the antibiotics were labeled based on their sensitivity to resistance development, in the third one they were labeled based on the resistant bacteria being gram-positive or gram-negative and in the fourth one they were divided by their mechanism of action. Discussion: There are neighborhoods in chemical space which are related to a higher risk of resistance development, as indicated by the antibiotics in this study – most of which seem quite susceptible to resistance development. There also seem to be areas of chemical space more related to resistance of gram-negative bacteria. It is not unlikely that resistance development has a stronger association to the use of antibiotics rather than chemical properties, but antibiotics that have a broad spectrum of activity and few serious side effects have been used extensively and that seems to have contributed to the development of resistance. It does seem that none of the antibiotics studied is immune to resistance development. Chemographics could be a useful tool in the search for novel antibiotics, and I believe that the only way for us to continue to be able to fight off bacteria is to use available antibiotic agents wisely and continue to devote research to find novel agents.
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eir.starradottir_chemographic.analysis.of.resistance.prune.antibiotics.pdf | 628,24 kB | Open | Complete Text | View/Open | |
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