TY - JOUR
T1 - Transcriptional profiles of the response of methicillin-resistant Staphylococcus aureus to pentacyclic triterpenoids
AU - Chung, Pooi Yin
AU - Chung, Lip Yong
AU - Navaratnam, Parasakthi
PY - 2013
Y1 - 2013
N2 - Staphylococcus aureus is an important human pathogen in both hospital and the community that has demonstrated resistance to all currently available antibiotics over the last two decades. Multidrug-resistant isolates of methicillin-resistant S. aureus (MRSA) exhibiting decreased susceptibilities to glycopeptides has also emerged, representing a crucial challenge for antimicrobial therapy and infection control. The availability of complete whole-genome nucleotide sequence data of various strains of S. aureus presents an opportunity to explore novel compounds and their targets to address the challenges presented by antimicrobial drug resistance in this organism. Study compounds a-amyrin [3?-hydroxy-urs-12-en-3-ol (AM)], betulinic acid [3?-hydroxy-20(29)-lupaene-28-oic acid (BA)] and betulinaldehyde [3?-hydroxy-20(29)-lupen-28-al (BE)] belong to pentacyclic triterpenoids and were reported to exhibit antimicrobial activities against bacteria and fungi, including S. aureus. The MIC values of these compounds against a reference strain of methicillin-resistant S. aureus (MRSA) (ATCC 43300) ranged from 64 ?g/ml to 512 ?g/ml. However, the response mechanisms of S. aureus to these compounds are still poorly understood. The transcription profile of reference strain of MRSA treated with sub-inhibitory concentrations of the three compounds was determined using Affymetrix GeneChips. The findings showed that these compounds regulate multiple desirable targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetase, ribosome and ?-lactam resistance pathways which could be further explored in the development of therapeutic agents for the treatment of S. aureus infections.
AB - Staphylococcus aureus is an important human pathogen in both hospital and the community that has demonstrated resistance to all currently available antibiotics over the last two decades. Multidrug-resistant isolates of methicillin-resistant S. aureus (MRSA) exhibiting decreased susceptibilities to glycopeptides has also emerged, representing a crucial challenge for antimicrobial therapy and infection control. The availability of complete whole-genome nucleotide sequence data of various strains of S. aureus presents an opportunity to explore novel compounds and their targets to address the challenges presented by antimicrobial drug resistance in this organism. Study compounds a-amyrin [3?-hydroxy-urs-12-en-3-ol (AM)], betulinic acid [3?-hydroxy-20(29)-lupaene-28-oic acid (BA)] and betulinaldehyde [3?-hydroxy-20(29)-lupen-28-al (BE)] belong to pentacyclic triterpenoids and were reported to exhibit antimicrobial activities against bacteria and fungi, including S. aureus. The MIC values of these compounds against a reference strain of methicillin-resistant S. aureus (MRSA) (ATCC 43300) ranged from 64 ?g/ml to 512 ?g/ml. However, the response mechanisms of S. aureus to these compounds are still poorly understood. The transcription profile of reference strain of MRSA treated with sub-inhibitory concentrations of the three compounds was determined using Affymetrix GeneChips. The findings showed that these compounds regulate multiple desirable targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetase, ribosome and ?-lactam resistance pathways which could be further explored in the development of therapeutic agents for the treatment of S. aureus infections.
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577688/pdf/pone.0056687.pdf
U2 - 10.1371/journal.pone.0056687
DO - 10.1371/journal.pone.0056687
M3 - Article
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e56687
ER -