Affiliation:
1. Department of Medical Microbiology, University of Zürich, Zürich, Switzerland
2. Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany
3. AO Research Institute, Davos, Switzerland
Abstract
ABSTRACT
Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the
ccpA
homologue (
saCOL1786
) in
Staphylococcus aureus
was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the Δ
ccpA
mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of
S. aureus
by down-regulating
RNAIII
, the effector molecule of the
agr
locus, and altering the transcription patterns of
hla
, encoding α-hemolysin, and
spa
, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant
S. aureus
strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant
S. aureus
strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased
cap
operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
173 articles.
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