Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance

Autor: Hans-Georg Sahl, Vesa P. Kontinen, Patrice Francois, Milla Pietiäinen, Manuela Tangomo, Vera Sass, Hanne-Leena Hyyryläinen, Jacques Schrenzel
Jazyk: angličtina
Rok vydání: 2009
Předmět:
ATP-Binding Cassette Transporters/genetics
ATP-binding cassette transporter
Cell Wall
Oligonucleotide Array Sequence Analysis
ddc:616
0303 health sciences
Antimicrobial
Antimicrobial Cationic Peptides/pharmacology
Proteins/pharmacology
3. Good health
DNA-Binding Proteins
RNA
Bacterial
Staphylococcus aureus/drug effects/genetics
medicine.drug
Biotechnology
Research Article
Staphylococcus aureus
Virulence Factors/genetics
lcsh:QH426-470
Virulence Factors
lcsh:Biotechnology
Antimicrobial peptides
Bacitracin
Microbial Sensitivity Tests
Biology
Regulon
Amphibian Proteins
Microbiology
03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
lcsh:TP248.13-248.65
Drug Resistance
Bacterial
Operon
medicine
Genetics
Animals
030304 developmental biology
Dermaseptin
Cell Wall/genetics
030306 microbiology
Bacterial Proteins/genetics
Gene Expression Profiling
Proteins
Gene Expression Regulation
Bacterial
Temporin
Amphibian Proteins/pharmacology
lcsh:Genetics
Mutation
ATP-Binding Cassette Transporters
DNA-Binding Proteins/genetics
RNA
Bacterial/genetics
Antimicrobial Cationic Peptides
Zdroj: BMC Genomics, Vol. 10, No 429 (2009) P. 429
BMC Genomics, Vol 10, Iss 1, p 429 (2009)
BMC Genomics
ISSN: 1471-2164
Popis: Background Understanding how pathogens respond to antimicrobial peptides, and how this compares to currently available antibiotics, is crucial for optimizing antimicrobial therapy. Staphylococcus aureus has several known resistance mechanisms against human cationic antimicrobial peptides (CAMPs). Gene expression changes in S. aureus strain Newman exposed to linear CAMPs were analyzed by DNA microarray. Three antimicrobial peptides were used in the analysis, two are derived from frog, temporin L and dermaseptin K4-S4(1-16), and the ovispirin-1 is obtained from sheep. Results The peptides induced the VraSR cell-wall regulon and several other genes that are also up-regulated in cells treated with vancomycin and other cell wall-active antibiotics. In addition to this similarity, three genes/operons were particularly strongly induced by the peptides: vraDE, SA0205 and SAS016, encoding an ABC transporter, a putative membrane-bound lysostaphin-like peptidase and a small functionally unknown protein, respectively. Ovispirin-1 and dermaseptin K4-S4(1-16), which disrupt lipid bilayers by the carpet mechanism, appeared to be strong inducers of the vraDE operon. We show that high level induction by ovispirin-1 is dependent on the amide modification of the peptide C-terminus. This suggests that the amide group has a crucial role in the activation of the Aps (GraRS) sensory system, the regulator of vraDE. In contrast, temporin L, which disrupts lipid bilayers by forming pores, revealed a weaker inducer of vraDE despite the C-terminal amide modification. Sensitivity testing with CAMPs and other antimicrobials suggested that VraDE is a transporter dedicated to resist bacitracin. We also showed that SA0205 belongs to the VraSR regulon. Furthermore, VraSR was shown to be important for resistance against a wide range of cell wall-active antibiotics and other antimicrobial agents including the amide-modified ovispirin-1, bacitracin, teicoplanin, cefotaxime and 10 other β-lactam antibiotics, chlorpromazine, thioridazine and EGTA. Conclusion Defense against different CAMPs involves not only general signaling pathways but also CAMP-specific ones. These results suggest that CAMPs or a mixture of CAMPs could constitute a potential additive to standard antibiotic treatment.
Databáze: OpenAIRE
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