Imperial College London
Alternate

DrBrianRobertson

Faculty of Medicine, Department of Infectious Disease

Reader in Systems Microbiology
 
 
 
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Contact

 

b.robertson

 
 
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Location

 

3.41Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Man:2018:10.1128/mSphere.00218-18,
author = {Man, DK-W and Kanno, T and Manzo, G and Robertson, BD and Lam, JKW and Mason, AJ},
doi = {10.1128/mSphere.00218-18},
journal = {MSPHERE},
title = {Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides},
url = {http://dx.doi.org/10.1128/mSphere.00218-18},
volume = {3},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The mycobacterial cell wall affords natural resistance to antibiotics. Antimicrobial peptides (AMPs) modify the surface properties of mycobacteria and can act synergistically with antibiotics from differing classes. Here, we investigate the response of Mycobacterium smegmatis to the presence of rifampin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs that are distinguished by the presence (D-LAK120-HP13) or absence (D-LAK120-A) of a kink-inducing proline. Using a combination of high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) metabolomics, diphenylhexatriene (DPH) fluorescence anisotropy measurements, and laurdan emission spectroscopy, we show that M. smegmatis responds to challenge with rifampin or capreomycin by substantially altering its metabolism and, in particular, by remodeling the cell envelope. Overall, the changes are consistent with a reduction of trehalose dimycolate and an increase of trehalose monomycolate and are associated with increased rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes, respectively, in mycomembrane metabolites and did not induce a significant increase in the rigidity of the mycolic acid layer. Furthermore, the response to rifampin or capreomycin was significantly reduced when these were combined with D-LAK120-HP13 and D-LAK120-A, respectively, suggesting a possible mechanism for the synergy of these combinations. The remodeling of the mycomembrane in M. smegmatis is therefore identified as an important countermeasure deployed against rifampin or capreomycin, but this can be mitigated and the efficacy of rifampin or capreomycin potentiated by combining the drug with AMPs.
AU  - Man,DK-W
AU  - Kanno,T
AU  - Manzo,G
AU  - Robertson,BD
AU  - Lam,JKW
AU  - Mason,AJ
DO  - 10.1128/mSphere.00218-18
PY  - 2018///
SN  - 2379-5042
TI  - Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides
T2  - MSPHERE
UR  - http://dx.doi.org/10.1128/mSphere.00218-18
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000441058200016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/62149
VL  - 3
ER  -
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