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Nonstable Staphylococcus aureus Small-Colony Variants Are Induced by Low pH and Sensitized to Antimicrobial Therapy by Phagolysosomal Alkalinization.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2016 Jan 15; Vol. 213 (2), pp. 305-13. Date of Electronic Publication: 2015 Jul 17. - Publication Year :
- 2016
-
Abstract
- Background: Staphylococcus aureus-infected patients treated with antibiotics that are effective in vitro often experience relapse of infection because the bacteria hide in privileged locations. These locations include abscesses and host cells, which contain low-pH compartments and are sites from which nonstable S. aureus small-colony variants (SCVs) are frequently recovered.<br />Methods: We assessed the effect of low pH on S. aureus colony phenotype and bacterial growth, using in vitro and in vivo models of long-term infection.<br />Results: We showed that low pH induced nonstable SCVs and nonreplicating persisters that are capable of regrowth. Within host cells, S. aureus was located in phagolysosomes, a low-pH compartment. Therapeutic neutralization of phagolysosomal pH with ammonium chloride, bafilomycin A1, or the antimalaria drug chloroquine reduced SCVs in infected host cells. In a systemic mouse infection model, treatment with chloroquine also reduced SCVs.<br />Conclusions: Our results show that the acidic environment favors formation of nonstable SCVs, which reflect the SCVs found in clinics. They also provide evidence that treatment with alkalinizing agents, together with antibiotics, may provide a novel translational strategy for eradicating persisting intracellular reservoirs of staphylococci. This approach may also be extended to other intracellular bacteria.<br /> (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Subjects :
- Ammonium Chloride pharmacology
Animals
Cell Line, Tumor
Chloroquine pharmacology
Gene Expression Regulation, Bacterial
Genetic Variation
Humans
Hydrogen-Ion Concentration
Macrolides pharmacology
Mice
Mice, Inbred C57BL
Staphylococcus aureus growth & development
Anti-Bacterial Agents pharmacology
Drug Resistance, Bacterial drug effects
Phagosomes chemistry
Staphylococcal Infections microbiology
Staphylococcus aureus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 213
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 26188074
- Full Text :
- https://doi.org/10.1093/infdis/jiv388