Baktería dormancy is survival strategy in response to stressful exposure to antibiotics taken by a patient for treatment. The dormant cells become tolerant to antibiotics and are killed at slower rate and survive sometimes. This is called ‘antibiotic tolerance’ which is unlike antibiotic resistance when bakteríur grow in the presence of antibiotics. Chronic or relapsing infections are attributed to antibiotic tolerance, for which there is no effective treatment. Phage therapy has long been considered but the dormant bacterial cells are non-responsive and refractory to known bacteriophages. Scientists of ETH Zurich have identified a new bacteriophage that uniquely replicates on deep stationary-phase cultures of Pseudomonas aeruginosa. Named ‘Paride’, this bacteriophage could kill deep-dormant P. aeruginosa by direct lytic replication. Interestingly, this novel phage reduced bacterial loads through phage-antibiotic synergy when meropenem antibiotic was added to cultures. Apparently, the novel phage could exploit weak spots in the physiology of dormant bacteria to overcome antibiotic tolerance. These weak spots could be targets of new treatment for chronic infections caused by dormant or inactive bacteria.
Most bacteria on Earth are in dormant state of reduced metabolic activity or in completely inactive form of spore. Such baktería cells can be readily resuscitated when required nutrients and molecules become available.
Baktería dormancy or inactivity is the survival strategy in response to stressful external environmental conditions like starvation or exposure to antibiotics taken by a patient for treatment. In later case, the dormant cells become tolerant to antibiotics because cellular processes targeted by the antibiotics to kill bakteríur are turned down. This phenomenon is called ‘sýklalyfjaþol' í því tilviki drepast bakteríur með hægari hraða og lifa stundum af (ólíkt því sem er í tilviki sýklalyfjaónæmi þegar bakteríur vaxa í návist sýklalyfja). Langvarandi sýkingar eða sýkingar sem koma aftur á rekja til sýklalyfjaþolinna bakteríufrumna í dvala, oft kallaðar „viðvarandi“, sem engin árangursrík meðferð er fyrir.
Phage therapy involving bacteriophages or phages (i.e., veirur that predate bakteríur), has long been considered for treating chronic infections by dormant or inactive bakteríur however this approach works when host baktería cells are undergoing growth. The dormant or inactive baktería cells, however, are non-responsive and refractory to the bacteriophages which either avoid adsorption to the baktería cell surfaces or hibernate in the dormant cells until resuscitation.
Known bacteriophages do not have ability to infect antibiotic-tolerant, deep-dormant or inactive bakteríur. It was thought that given diversity, phages with ability to infect dormant cells may exist in nature. Researchers have now identified one such novel bacteriophage for the first time.
Í nýlega birtri rannsókn hafa vísindamenn á ETH Zurich tilkynnt um einangrun nýs bakteríuvefs sem endurtekur sig á einstakan hátt á djúpum kyrrstöðu-fasa ræktun Pseudomonas aeruginosa á rannsóknarstofunni. Þeir hafa nefnt þennan bakteríusýki Paride. Þessi fagur gæti drepið djúpt sofandi P. aeruginosa með beinni lýtískri afritun. Athyglisvert er að þessi nýja fagur minnkaði bakteríuálag með samvirkni faga og sýklalyfja þegar meropenem sýklalyfi var bætt við P. aeruginosa-fagaræktun.
Eins og gefur að skilja gæti hin nýja fagur nýtt sér veika bletti í lífeðlisfræði sofandi baktería til að sigrast á sýklalyfjaþoli. Þessir veiku blettir gætu verið skotmark nýrrar meðferðar við langvinnum sýkingum af völdum sofandi eða óvirkra baktería.
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Tilvísun:
- Maffei, E., Woischnig, AK., Burkolter, MR o.fl. Phage Paride getur drepið sofandi, sýklalyfjaþolnar frumur Pseudomonas aeruginosa með beinni sýklaafritun. Nat Commun 15, 175 (2024). https://doi.org/10.1038/s41467-023-44157-3
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