Bacterial aminoacyl phospholipids – Biosynthesis and role in basic cellular processes and pathogenicity

Slavetinsky, Christoph; Kuhn, Sebastian; Peschel, Andreas

doi:10.1016/j.bbalip.2016.11.013

Cited by 60 publications

(66 citation statements)

References 92 publications

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“…Such lipidmediated functional plasticity plays an important role in the survival mechanisms of bacteria exposed to environmental stress. [2] In the case of the Gram positive opportunistic pathogen Staphylococcus aureus, increased synthesis of the aminoacyl lipid lysyl-phosphatidylglycerol (L-PG), has been shown to protect the bacteria from defensive cationic membrane-active antimicrobial peptides (AMPs) and thus allow them colonise human epithelia and even establish, maintain and spread infections [3]. The formation of ion pairs between the phosphate of the phosphatidylcholine (PG) headgroup and the amines of the L-PG headgroup, has been shown to fine tune both the charge and ordering of lipids in reconstituted S. aureus lipid membranes, thus attenuating interaction with AMPs.…”

Section: Introductionmentioning

confidence: 99%

A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids

Schmid

Wölk

Giselbrecht

et al. 2018

Colloids and Surfaces B: Biointerfaces

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Investigating lipid ion pair formation is important for understanding the mechanisms of lipid-mediated drug resistance in bacteria. In this study we have used the charged amphiphiles dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyldimethylammonium bromide (DHDAB), as a model to evaluate the formation of ion pairs by a combined Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis. FTIR was employed to study the environment of the DPPC headgroup phosphate and lipid/surfactant alkane chains, in vesicles formed by the two amphiphiles mixed in various molar ratios. An increase of the absorbance ratio of 1221-1201 cm in the asymmetric phosphate stretching mode was found to follow a sigmoidal relationship with the proportion of DHDAB, increasing to a plateau above a DPPG/DHDAB 1:1 molar ratio of, providing evidence that the PG headgroup phosphate is involved in ion pairing. A consistent red shift was measured for the position of the symmetric CH stretch band for the lipid/surfactant 1:1 molar ratio mixture, which is indicative of an increased ordering of the hydrophobic chains. The DSC experiments yielded information about the thermotropic and the mixing behaviour of the lipid/surfactant systems. DPPG and DHDAB seem to form an ion pair with cluster compound characteristics at the equimolar ratio. Most interestingly, the DPPG/DHDAB 2:1 molar ratio mixture is characterized by strong intermolecular interactions, which result in a pronounced stabilization of the gel phase, possibly through the formation of a closely-associated ion triplet configuration in which the charges are delocalised across the headgroups.

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Section: Introductionmentioning

confidence: 99%

A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids

Schmid

Wölk

Giselbrecht

et al. 2018

Colloids and Surfaces B: Biointerfaces

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“…Like in E. coli there is in S. aureus also a predominant positive charged phospholipid, the Lys-PG (Gould & Lennarz, 1970), which is synthesized by MprF (Ernst et al, 2015;Peschel et al, 2001). Lys-PG, which yields 20%-40% of staphylococcus total membrane phospholipids, causes resistance against cationic antimicrobial compounds through ionic repulsion (Slavetinsky, Kuhn, & Peschel, 2016). Given that, gram-positive bacteria lack the Lol system it is still possible that Asp+2 strengthens the anchoring of the corresponding Lpp to the membrane via the interaction with the positively charged Lys-PG.…”

Section: Discussionmentioning

confidence: 99%

Aspartate tightens the anchoring of staphylococcal lipoproteins to the cytoplasmic membrane

2017

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In gram‐negative bacteria, the ABC transporter LolCDE complex translocates outer membrane‐specific lipoproteins (Lpp) from the inner membrane to the outer membrane. Lpp possessing aspartate (Asp) at position +2 are not translocated because it functions as a LolCDE avoidance signal. In gram‐positive bacteria, lacking an outer membrane and the Lol system, Lpp are only anchored at the outer leaflet of the cytoplasmic membrane. However, the release of Lpp particularly in pathogenic or commensal species is crucial for immune modulation. Here, we provide evidence that in Staphylococcus aureus Asp at position +2 plays a role in withholding Lpp to the cytoplasmic membrane. Screening of published exoproteomic data of S. aureus revealed that Lpp mainly with Gly or Ser at position +2 were found in exoproteome, but there was no Lpp with Asp+2. The occurrence of Lpp with Asp+2 is infrequent in gram‐positive bacteria. In S. aureus USA300 only seven of the 67 Lpp possess Asp+2; among them five Lpp represented Lpl lipoproteins involved in host cell invasion. Our study demonstrated that replacing the Asp+2 present in Lpl8 with a Ser enhances its release into the supernatant. However, there is no different release of Asp+2 and Ser+2 in mprF mutant that lacks the positive charge of lysyl‐phosphatidylglycerol (Lys‐PG). Moreover, substitution of Ser+2 by Asp in SitC (MntC) did not lead to a decreased release indicating that in staphylococci positions +3 and +4 might also be important for a tighter anchoring of Lpp. Here, we show that Asp in position +2 and adjacent amino acids contribute in tightening the anchoring of Lpp by interaction of the negative charged Asp with the positive charged Lys‐PG.

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“…The aminoacyl lipids produced by a wide range of bacteria are becoming increasingly recognized as clinically relevant virulence factors, due to the role they play in phenotypic adaptations to the physical and biochemical stressors which confer intrinsic defence against infection . The most widely studied of these lipids is lysyl‐phosphatidylglycerol (LPG), for which the genomic regulation and biosynthetic pathways in Staphylococcus aureus , have recently been elucidated in some detail . Data from microbiological assays, has shown that an increased proportion of LPG in S. aureus membranes correlates with resistance to both host defensive peptides and membrane‐active therapeutic antibiotics .…”

Section: Figurementioning

confidence: 99%

Phase Diagram for a Lysyl‐Phosphatidylglycerol Analogue in Biomimetic Mixed Monolayers with Phosphatidylglycerol: Insights into the Tunable Properties of Bacterial Membranes

et al. 2020

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Ion pairing between the major phospholipids of the Staphylococcus aureus plasma membrane (phosphatidylglycerol -PG and lysyl-phosphatidylglycerol -LPG) confers resistance to antimicrobial peptides and other antibiotics. We developed 3adLPG, a stable synthetic analogue which can substitute for the highy-labile native LPG, in biophysical experiments examining the membrane-protecting role of lipid ion pairing, in S. aureus and other important bacteria. Here we examine the surface charge and lipid packing characteristics of synthetic biomimetic mixtures of DPPG and DP3adLPG in Langmuir monolayers, using a combination of complementary surfaceprobing techniques such as infrared reflection-absorption spectroscopy and grazing-incidence x-ray diffraction. The resultant phase diagram for the ion paired lipids sheds light on the mixing behavior of lipids in monolayer models of resistant phenotype bacterial membranes, and provides a platform for future biophysical studies.The aminoacyl lipids produced by a wide range of bacteria are becoming increasingly recognized as clinically relevant virulence factors, due to the role they play in phenotypic adaptations to the physical and biochemical stressors which confer intrinsic defence against infection. [1,2] The most widely studied of these lipids is lysyl-phosphatidylglycerol (LPG), for which the genomic regulation and biosynthetic pathways in Staphylococcus aureus, have recently been elucidated in some detail. [3,4] Data from microbiological assays, has shown that an increased proportion of LPG in S. aureus membranes correlates with resistance to both host defensive peptides [5] and membrane-active therapeutic antibiotics. [6] The mechanisms facilitating such resistances are assumed to involve the tuning of target membrane physical properties, notably those of interfacial charge and lipid ordering, which are influenced by the LPG content in the bacteria membranes. [7] Biophysical investigations into these phenomena have been hampered by the labile nature of native LPG, which is readily hydrolysed under mild conditions, therefore exposing any such study to the risk of artefact. [8,9] To this end, stable LPG analogues have been synthesized. One such analogue, lysyl-phosphatidylethanolamine (LPE) exhibited an inhibitory effect on antimicrobial peptide activity when incorporated into vesicles containing phosphatidylglycerol (PG). [10] A second analogue, 3-aza-dehydroxy lysyl-phosphatidylglycerol (3adLPG), facilitated enhanced membrane ordering and antimicrobial peptide resistance when mixed with PG under mildly acidic conditions, [11] which are known to promote PG/LPG ion pair formation in model bacterial membranes. [12] In order to gain a better understanding of the influence of lipid ion pairing on membrane structure and interfacial properties, we conducted a high-resolution study of biomimetic mixtures of dipalmitoyl-3adLPG and DPPG in Langmuir monolayers.The natural phospholipid composition ( Figure 1A) observed in different S. aureus strains is dominated by PG ( � 40-70 %) and...

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Bacterial aminoacyl phospholipids – Biosynthesis and role in basic cellular processes and pathogenicity

Cited by 60 publications

References 92 publications

A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids

A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids

Aspartate tightens the anchoring of staphylococcal lipoproteins to the cytoplasmic membrane

Phase Diagram for a Lysyl‐Phosphatidylglycerol Analogue in Biomimetic Mixed Monolayers with Phosphatidylglycerol: Insights into the Tunable Properties of Bacterial Membranes

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