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Evaluating the pote...
Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections
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- Berryhill, Brandon A. (författare)
- Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
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- Huseby, Douglas L (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- McCall, Ingrid C. (författare)
- Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
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- Hughes, Diarmaid, 1956- (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi,Institutionen för medicinsk biokemi och mikrobiologi
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- Levin, Bruce R. (författare)
- Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
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Emory Univ, Dept Biol, Atlanta, GA 30322 USA Institutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)
- 2021-03
- 2021
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:10
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- In response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYOSa, for combination phage and antibiotic treatment of Staphylococcus aureus infections. This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYOSa. Because of the mode of action of PYOSa, S. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, PYOSa does not clear populations of S. aureus. Due to the ascent of a phenotyically diverse array of small-colony variants following an initial demise, the bacterial populations return to densities similar to that of phage-free controls. Using a combination of mathematical modeling and in vitro experiments, we postulate and present evidence for a mechanism to account for the demise-resurrection dynamics of PYOSa and S. aureus. Critically for phage therapy, our experimental results suggest that treatment with PYOSa followed by bactericidal antibiotics can clear populations of S. aureus more effectively than the antibiotics alone.
Ämnesord
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- phage therapy
- population dynamics
- Staphylococcus aureus
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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