PMID- 19858261
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20220410
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 54
IP  - 1
DP  - 2010 Jan
TI  - Influence of tigecycline on expression of virulence factors in biofilm-associated 
      cells of methicillin-resistant Staphylococcus aureus.
PG  - 380-7
LID - 10.1128/AAC.00155-09 [doi]
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections are complicated by 
      the ability of the organism to grow in surface-adhered biofilms on a multitude of 
      abiotic and biological surfaces. These multicellular communities are notoriously 
      difficult to eradicate with antimicrobial therapy. Cells within the biofilm may 
      be exposed to a sublethal concentration of the antimicrobial due to the metabolic 
      and phenotypic diversity of the biofilm-associated cells or the protection 
      offered by the biofilm structure. In the present study, the influence of a 
      sublethal concentration of tigecycline on biofilms formed by an epidemic MRSA-16 
      isolate was investigated by transcriptome analysis. In the presence of the drug, 
      309 genes were upregulated and 213 genes were downregulated by more than twofold 
      in comparison to the levels of gene regulation detected for the controls not 
      grown in the presence of the drug. Microarray data were validated by real-time 
      reverse transcription-PCR and phenotypic assays. Tigecycline altered the 
      expression of a number of genes encoding proteins considered to be crucial for 
      the virulence of S. aureus. These included the reduced expression of icaC, which 
      is involved in polysaccharide intercellular adhesin production and biofilm 
      development; the upregulation of fnbA, clfB, and cna, which encode adhesins which 
      attach to human proteins; and the downregulation of the cap genes, which mediate 
      the synthesis of the capsule polysaccharide. The expression of tst, which encodes 
      toxic shock syndrome toxin 1 (TSST-1), was also significantly reduced; and an 
      assay performed to quantify TSST-1 showed that the level of toxin production by 
      cells treated with tigecycline decreased by 10-fold (P < 0.001) compared to the 
      level of production by untreated control cells. This study suggests that 
      tigecycline may reduce the expression of important virulence factors in S. aureus 
      and supports further investigation to determine whether it could be a useful 
      adjunct to therapy for the treatment of biofilm-mediated infections.
FAU - Smith, Karen
AU  - Smith K
AD  - Department of Biological and Biomedical Sciences, Glasgow Caledonian University, 
      Cowcaddens Road, Glasgow G4 0BA, United Kingdom.
FAU - Gould, Katherine A
AU  - Gould KA
FAU - Ramage, Gordon
AU  - Ramage G
FAU - Gemmell, Curtis G
AU  - Gemmell CG
FAU - Hinds, Jason
AU  - Hinds J
FAU - Lang, Sue
AU  - Lang S
LA  - eng
GR  - 080039/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091026
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (RNA, Bacterial)
RN  - 0 (Virulence Factors)
RN  - 70JE2N95KR (Tigecycline)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Adhesins, Bacterial/biosynthesis
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Bacterial Capsules/chemistry/metabolism
MH  - Bacterial Proteins/biosynthesis
MH  - Biofilms/*drug effects
MH  - Methicillin-Resistant Staphylococcus aureus/drug effects/*metabolism
MH  - Minocycline/*analogs & derivatives/pharmacology
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Bacterial/biosynthesis/isolation & purification
MH  - Reproducibility of Results
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tigecycline
MH  - Virulence Factors/*biosynthesis
PMC - PMC2798542
EDAT- 2009/10/28 06:00
MHDA- 2010/03/17 06:00
PMCR- 2010/07/01
CRDT- 2009/10/28 06:00
PHST- 2009/10/28 06:00 [entrez]
PHST- 2009/10/28 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - AAC.00155-09 [pii]
AID - 0155-09 [pii]
AID - 10.1128/AAC.00155-09 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2010 Jan;54(1):380-7. doi: 10.1128/AAC.00155-09. 
      Epub 2009 Oct 26.