Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis

Scheinpflug, Kathi; Wenzel, Michaela; Krylova, Oxana; Bandow, Julia E.; Dathe, Margitta; Strahl, Henrik

doi:10.1038/srep44332

Cited by 102 publications

(114 citation statements)

References 68 publications

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“…The WALP23 artificial transmembrane helix (sequence AW 2 L(AL) 8 W 2 A) was previously shown, when fused to mGFP, to provide a good general membrane label when expressed in B. subtilis (Scheinpflug et al, ). The Scheinpflug construct was under xylose‐inducible control.…”

Section: Methodsmentioning

confidence: 99%

Microfluidic time‐lapse analysis and reevaluation of the Bacillus subtilis cell cycle

Lee

Errington

2019

MicrobiologyOpen

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Recent studies taking advantage of automated single‐cell time‐lapse analysis have reignited interest in the bacterial cell cycle. Several studies have highlighted alternative models, such as Sizer and Adder, which differ essentially in relation to whether cells can measure their present size or their amount of growth since birth. Most of the recent work has been done with Escherichia coli. We set out to study the well‐characterized Gram‐positive bacterium, Bacillus subtilis, at the single‐cell level, using an accurate fluorescent marker for division as well as a marker for completion of chromosome replication. Our results are consistent with the Adder model in both fast and slow growth conditions tested, and with Sizer but only at the slower growth rate. We also find that cell size variation arises not only from the expected variation in size at division but also that division site offset from mid‐cell contributes to a significant degree. Finally, although traditional cell cycle models imply a strong connection between the termination of a round of replication and subsequent division, we find that at the single‐cell level these events are largely disconnected.

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Section: Methodsmentioning

confidence: 99%

Microfluidic time‐lapse analysis and reevaluation of the Bacillus subtilis cell cycle

Lee

Errington

2019

MicrobiologyOpen

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“…To identify commonalities of the physiological impact of allicin to that of other antibacterial agents, we compared the proteomic response to allicin to a response library containing 44 proteomic responses of B. subtilis to known antimicrobial agents . Regarding the number of induced proteins, with 56 marker proteins, allicin evoked the most complex response in B. subtilis among the tested compounds.…”

Section: Resultsmentioning

confidence: 99%

Interspecies Comparison of the Bacterial Response to Allicin Reveals Species‐Specific Defense Strategies

et al. 2019

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Allicin, a broad‐spectrum antimicrobial agent from garlic, disrupts thiol and redox homeostasis, proteostasis, and cell membrane integrity. Since medicine demands antimicrobials with so far unexploited mechanisms, allicin is a promising lead structure. While progress is being made in unraveling its mode of action, little is known on bacterial adaptation strategies. Some isolates of Pseudomonas aeruginosa and Escherichia coli withstand exposure to high allicin concentrations due to as yet unknown mechanisms. To elucidate resistance and sensitivity‐conferring cellular processes, the acute proteomic responses of a resistant P. aeruginosa strain and the sensitive species Bacillus subtilis are compared to the published proteomic response of E. coli to allicin treatment. The cellular defense strategies share functional features: proteins involved in translation and maintenance of protein quality, redox homeostasis, and cell envelope modification are upregulated. In both Gram‐negative species, protein synthesis of the majority of proteins is downregulated while the Gram‐positive B. subtilis responded by upregulation of multiple regulons. A comparison of the B. subtilis proteomic response to a library of responses to antibiotic treatment reveals 30 proteins specifically upregulated by allicin. Upregulated oxidative stress proteins are shared with nitrofurantoin and diamide. Microscopy‐based assays further indicate that in B. subtilis cell wall integrity is impaired.

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“…Nevertheless, laurdan generalised polarization has been used in e.g. Bacillus subtilis to detect the effect of challenge with a synthetic cyclic hexapeptide cWFW 35 and the organisation of the bacterial membrane by flotillins 36 and MreB 37 . Significant changes (p < 0.05) in laurdan GP were observed for M. smegmatis mc 2 155 challenged during growth with ¾ MIC or FIC capreomycin or its combinations with D-LAK120A or D-LAK120-HP13 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Rifampicin or capreomycin induced remodelling of theMycobacterium smegmatismycolic acid layer is mitigated in synergistic combinations with cationic antimicrobial peptides

Man

Kanno

Manzo

et al. 2018

Preprint

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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 rifampicin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs; 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 (HR-MAS) NMR of bacteria, diphenylhexatriene (DPH) fluorescence anisotropy and laurdan emission spectroscopy we show that M. smegmatis responds to challenge with rifampicin or capreomycin by substantially altering its metabolism and, in particular, by remodelling the cell envelope. In NMR spectra of bacteria, reductions in intensity for mycolic acid lipid -(CH2)-, -CH3, R2CH-COOH, R2CH-OH and also -CH2-(CH=CH)-and -CH=CH-resonances were observed following challenge with rifampicin and capreomycin, while the latter also caused an increase in trehalose. These changes are consistent with a reduction of trehalose dimycolate and increase of trehalose monomycolate and are associated with an increase in rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampicin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes respectively in these metabolites and did not induce a significant increase in rigidity of the mycolic acid layer. Further, the response to rifampicin or capreomycin was significantly reduced when these were combined respectively with D-LAK120-HP13 and D-LAK120-A, suggesting a possible mechanism for the synergy of these combinations. The remodelling of the mycomembrane in M. smegmatis is therefore identified as an important countermeasure deployed against rifampicin or capreomycin, but this can be mitigated, and rifampicin or capreomycin efficacy potentiated, by combining with AMPs.

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Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis

Cited by 102 publications

References 68 publications

Microfluidic time‐lapse analysis and reevaluation of the Bacillus subtilis cell cycle

Microfluidic time‐lapse analysis and reevaluation of the Bacillus subtilis cell cycle

Interspecies Comparison of the Bacterial Response to Allicin Reveals Species‐Specific Defense Strategies

Rifampicin or capreomycin induced remodelling of theMycobacterium smegmatismycolic acid layer is mitigated in synergistic combinations with cationic antimicrobial peptides

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