Document Detail

Cardiolipin biosynthesis in Streptococcus mutans is regulated in response to external pH.
MedLine Citation:
PMID:  22628481     Owner:  NLM     Status:  MEDLINE    
Streptococcus mutans, a causative agent of dental caries in humans, adapts to changing environmental conditions, such as pH, in order to survive and cause disease in the oral cavity. Previously, we have shown that S. mutans increases the proportion of monounsaturated membrane fatty acids as part of its acid-adaptive strategy. Membrane lipids function as carriers of membrane fatty acids and therefore it was hypothesized that lipid backbones themselves could participate in the acid adaptation process. Lipids have been shown to protect other bacterial species from rapid changes in their environment, such as shifts in osmolality and the need for long-term survival. In the present study, we have determined the contribution of cardiolipin (CL) to acid resistance in S. mutans. Two ORFs have been identified in the S. mutans genome that encode presumptive synthetic enzymes for the acidic phospholipids: phosphatidylglycerol (PG) synthase (pgsA, SMU.2151c) and CL synthase (cls, SMU.988), which is responsible for condensing two molecules of PG to create CL. A deletion mutant of the presumptive cls gene was created using PCR-mediated cloning; however, attempts to delete pgsA were unsuccessful, indicating that pgsA may be essential. Loss of the presumptive cls gene resulted in the inability of the mutant strain to produce CL, indicating that SMU.988 encodes CL synthase. The defect in cls rendered the mutant acid sensitive, indicating that CL is required for acid adaptation in S. mutans. Addition of exogenous CL to the mutant strain alleviated acid sensitivity. MS indicated that S. mutans could assimilate exogenous CL into the membrane, halting endogenous CL incorporation. This phenomenon was not due to repression, as a cls gene transcriptional reporter fusion exhibited elevated activity when cells were supplemented with exogenous CL. Lipid analysis, via MS, indicated that CL is a reservoir for monounsaturated fatty acids in S. mutans. We demonstrated that the cls mutant exhibits elevated F-ATPase activity but it is nevertheless unable to maintain the normal membrane proton gradient, indicating cytoplasmic acidification. We conclude that the control of lipid backbone synthesis is part of the acid-adaptive repertoire of S. mutans.
Matthew E MacGilvray; John D Lapek; Alan E Friedman; Robert G Quivey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-24
Journal Detail:
Title:  Microbiology (Reading, England)     Volume:  158     ISSN:  1465-2080     ISO Abbreviation:  Microbiology (Reading, Engl.)     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-03     Completed Date:  2012-11-30     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  9430468     Medline TA:  Microbiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  2133-43     Citation Subset:  IM    
Center for Oral Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
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MeSH Terms
Acids / metabolism*
Bacterial Proteins / genetics,  metabolism
Biosynthetic Pathways
Cardiolipins / biosynthesis*
Gene Expression Regulation, Bacterial
Hydrogen-Ion Concentration
Streptococcus mutans / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Acids; 0/Bacterial Proteins; 0/Cardiolipins

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