Omega-3 fatty acids in cellular membranes: a unified concept

The Omega-3 fatty acid DHA (docosahexaenoic acid, 22:6) and its sister molecule EPA (eicosapentaenoic acid, 20:5) are highlighted here. These highly unsaturated fatty acids are widespread in nature, especially in the marine environment, and are essential in membranes ranging from deep sea bacteria to human neurons. Studies of DHA/EPA in bacteria have led to a working model on the structural roles of these molecules and are described in this review. The main points are: (a) genomic analysis shows that genes encoding the DHA/EPA pathways are similar, supporting the idea that structural roles in bacteria might be similar, (b) biochemical analysis shows that DHA and EPA are produced in bacteria by a polyketide process distinct from the pathway of plants and animals; this allows DHA and EPA to be produced in anaerobic or oxygen-limited environments, (c) regulatory systems triggered by temperature and pressure have been identified and studied, and add to the understanding of the roles of these molecules, (d) DHA/EPA bacteria are located almost exclusively in the marine environment, raising the prospect of an important linkage between membrane processes and marine conditions, (e) physiological studies of an EPA recombinant of E. coli show that EPA phospholipids contribute essential fluidity to the bilayer and that an EPA-enriched membrane supports a respiratory lifestyle dependent on proton bioenergetics; the EPA recombinant displays other physiological properties likely attributed to high levels of EPA in the bilayer, and (f) chemical studies such as chemical dynamic modeling support the idea that DHA and presumably EPA contribute hyperfluidizing properties to the membrane. We hypothesize that DHA/EPA phospholipids contribute fluidity and other properties to the bilayer which distinguish these highly unsaturated chains from monounsaturates and polyunsaturates such as 18:2 and 18:3. We further hypothesize that the structural properties of DHA/EPA functioning in bacteria are also harnessed by higher organisms for enhancing crucial membrane processes including photosynthesis and energy transduction.     

Copy number variation of a fatty acid desaturase gene Fads2 associated with ecological divergence in freshwater stickleback populations

Fitness of aquatic animals can be limited by the scarcity of nutrients such as long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA). DHA availability from diet varies among aquatic habitats, imposing different selective pressures on resident animals to optimize DHA acquisition and synthesis. For example, DHA is generally poor in freshwater ecosystems compared to marine ecosystems. Our previous work revealed that, relative to marine fishes, several freshwater fishes evolved higher copy numbers of the fatty acid desaturase2 (Fads2) gene, which encodes essential enzymes for DHA biosynthesis, likely compensating for the limited availability of DHA in freshwater. Here, we demonstrate that Fads2 copy number also varies between freshwater sticklebacks inhabiting lakes and streams with stream fish having higher Fads2 copy number. Additionally, populations with benthic-like morphology possessed higher Fads2 copy number than those with planktivore-like morphology. This may be because benthic-like fish mainly feed on DHA-deficient prey such as macroinvertebrates whereas planktivore-like fish forage more regularly on DHA-rich prey, like copepods. Our results suggest that Fads2 copy number variation arises from ecological divergence not only between organisms exploiting marine and freshwater habitats but also between freshwater organisms exploiting divergent resources.     

A second examination of predation on pelagic copepods by the brittle star Astrotoma agassizii

Euchaeta antarctica and Calanoides acutus, common pelagic copepodsof the Southern Ocean, dominate stomach contents of the brittlestar Astrotoma agassizii from the South Georgia shelf in November–December.This finding does not support our earlier hypothesis of restrictedfeeding by Astrotoma in austral fall on these copepods duringtheir seasonal migration.     

Taxonomic differences in the essential fatty acid composition of groups of freshwater zooplankton relate to reproductive demands and generation time

1. Marked differences were observed in the total fatty acid concentrations and essential fatty acid (EFA) distributions of co-existing freshwater copepods and cladocerans in four large lake systems (lakes Michigan, Erie, Ontario and Champlain) over two growing seasons. These patterns appeared independent of lake seston EFA composition.
2. Compared to the cladocerans, calanoid and cyclopoid copepods contained significantly higher concentrations of total fatty acids and docosahexaenoic acid (DHA), an EFA abundant in fish. Calanoids and cladocerans contained similar levels of eicosapentaenoic acid (EPA), but cladocerans showed EPA : DHA ratios consistently greater than those of the available seston food source. Alpha-linolenic acid was most abundant in the herbivorous cladocerans, Daphnia and Holopedium , while the highest concentrations of arachidonic acid were found in the predatory cladocerans, Bythotrephes longimanus and Leptodora kindtii .
3. The distinct EFA accumulation patterns between cladoceran and copepod zooplankton suggest metabolic regulation of certain EFAs to meet the particular physiological demands and ecological strategies of these different zooplankton groups. Cladocerans may accumulate EPA directly from their diet, or through transformation of dietary materials to facilitate rapid somatic growth and enhance reproduction due to their short generation time. In contrast, copepods may retain DHA to increase their cell membrane fluidity in order to remain active over the winter due to their longer generation time and life cycle.
4. Consistent EFA differences between zooplankton groups may have implications regarding the somatic growth and reproductive success of different zooplankton taxa as well as the nutritional value of various zooplankton groups for larval and planktivorous fish.     

Temperature-induced changes in fatty acid dynamics of the intertidal grazer Platychelipus littoralis (Crustacea,Copepoda, Harpacticoida): Insights from a short-term feeding experiment

Dietary lipids, and in particular the essential fatty acids (EFA), EPA (20:5ω3) and DHA (22:6ω3), guarantee the well-being of animals and are recognized for their potential bottom-up control on animal populations. They are introduced in marine ecosystems through primary producers and when grazed upon, they are consumed, incorporated or modified by first-level consumers. As the availability of EFA in the ecosystem is affected by ambient temperature, the predicted rise in ocean temperature might alter the availability of these EFA at the basis of marine food webs. Despite the FA bioconversion capacity of certain benthic copepod species, their lipid (FA) response to varying temperatures is understudied. Therefore, the temperate, intertidal copepod Platychelipus littoralis was offered a mono and mixed diatom diet at 4, 15 °C (normal range) and at 24 °C (elevated temperature) to investigate the combined effects of temperature and resource availability on its FA content and composition. P. littoralis showed a flexible thermal acclimation response. Cold exposure increased the degree of FA unsaturation and the EPA%, and induced a shift towards shorter chain FA in the copepod’s membranes. Furthermore, a mixed diet reduced the impact of heat stress on the copepod’s membrane FA composition. Temperature affected the trophic transfer of EPA and DHA differently. While dietary resources could fully compensate for the temperature effects on total lipid and EPA content in the copepods, no such counterweigh was observed for the DHA dynamics. Heat stress lowered the DHA concentration in copepods regardless of the resources available and this implies negative effects for higher trophic levels.     

Lipid dynamics and feeding of dominant Antarctic calanoid copepods in the eastern Weddell Sea in December

Lipid content, fatty acid composition, and feeding activity of the dominant Antarctic copepods, Calanoides acutus, Calanus propinquus, and Metridia gerlachei, were studied at a quasi-permanent station in the eastern Weddell Sea in December 2003. During 3 weeks of the spring phytoplankton development, total lipid levels of females and copepodite stages V (CVs) of C. acutus were almost doubled. Meanwhile, only a slight increase in total lipid content occurred in M. gerlachei, and no clear trend was observed in lipids of C. propinquus females. The pronounced increase of lipids in C. acutus was due to an accumulation of wax esters. The proportion of wax esters in the lipids of M. gerlachei was clearly lower, while triacylglycerols played a more important role. In C. propinquus, triacylglycerols were the only neutral lipid class. There were no pronounced changes in the feeding activity of M. gerlachei, whereas the feeding activity of C. acutus had rapidly increased with the development of the phytoplankton bloom in December, which explains its rapid lipid accumulation. The combination of gut content and fatty acid trophic marker analyses showed that C. acutus was feeding predominantly on diatoms. The typical diatom fatty acid marker, 16:1(n-7), slightly decreased and the tracer for flagellates, 18:4(n-3), increased in females and CVs of C. acutus. This shift indicates the time, when the significance of flagellates started to increase. The three copepod species exhibited different patterns of lipid accumulation in relation to their trophic niches and different duration of their active phases. The investigations filled a crucial data gap in the seasonal lipid dynamics of dominant calanoid copepods in the Weddell Sea in December and support earlier hypotheses on their energetic adaptations and life cycle strategies.     

Adaptive Changes in Membrane Lipids of Barophilic Bacteria in Response to Changes in Growth Pressure

The lipid compositions of barophilic bacterial strains which contained docosahexaenoic acid (DHA [22:6n-3]) were examined, and the adaptive changes of these compositions were analyzed in response to growth pressure. In the facultatively barophilic strain 16C1, phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) were major components which had the same fatty acid chains. However, in PE, monounsaturated fatty acids such as hexadecenoic acid were major components, and DHA accounted for only 3.7% of the total fatty acids, while in PG, DHA accounted for 29.6% of the total fatty acids. In response to an increase in growth pressure in strain 16C1, the amounts of saturated fatty acids in PE were reduced, and these decreases were mainly balanced by an increase in unsaturated fatty acids, including DHA. In PG, the decrease in saturated fatty acids was mainly balanced by an increase in DHA. Similar adaptive changes in fatty acid composition were observed in response to growth pressure in obligately barophilic strain 2D2. Furthermore, these adaptive changes in response were also observed in response to low temperature in strain 16C1. These results confirm that the general shift from saturated to unsaturated fatty acids including DHA is one of the adaptive changes in response to increases in pressure and suggest that DHA may play a role in maintaining the proper fluidity of membrane lipids under high pressure.     

Tracking seasonal changes in North Sea zooplankton trophic dynamics using stable isotopes

Trophodynamics of meso-zooplankton in the North Sea (NS) were assessed at a site in the southern NS, and at a shallow and a deep site in the central NS. Offshore and neritic species from different ecological niches, including Calanus spp., Temora spp. and Sagitta spp., were collected during seven cruises over 14 months from 2007 to 2008. Bulk stable isotope (SI) analysis, phospholipid-derived fatty acid (PLFA) compositions, and δ ¹³C_PLFA data of meso-zooplankton and particulate organic matter (POM) were used to describe changes in zooplankton relative trophic positions (RTPs) and trophodynamics. The aim of the study was to test the hypothesis that the RTPs of zooplankton in the North Sea vary spatially and seasonally, in response to hydrographic variability, with the microbial food web playing an important role at times. Zooplankton RTPs tended to be higher during winter and lower during the phytoplankton bloom in spring. RTPs were highest for predators such as Sagitta sp. and Calanus helgolandicus and lowest for small copepods such as Pseudocalanus elongatus and zoea larvae (Brachyura). δ ¹⁵N_POM-based RTPs were only moderate surrogates for animals’ ecological niches, because of the plasticity in source materials from the herbivorous and the microbial loop food web. Common (16:0) and essential (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) structural lipids showed relatively constant abundances. This could be explained by incorporation of PLFAs with δ ¹³C signatures which followed seasonal changes in bulk δ ¹³C_POM and PLFA δ ¹³C_POM signatures. This study highlighted the complementarity of three biogeochemical approaches for trophodynamic studies and substantiated conceptual views of size-based food web analysis, in which small individuals of large species may be functionally equivalent to large individuals of small species. Seasonal and spatial variability was also important in altering the relative importance of the herbivorous and microbial food webs.     

Can muscle fatty acid signature be used to distinguish diets during the marine trophic phase of sea lamprey (Petromyzon marinus, L.)?

Characterization of muscle and liver fatty acid profiles, determination of liver lipogenic and lipolytic activities and estimation of liver fatty elongases and desaturases activities of sea lamprey were realized at the beginning of the spawning migration. The muscle fatty acid profile was consistent with the location of capture, and revealed that animals captured far upstream from the river mouth presented the lowest C18:1ω9 levels and the highest relative proportions of C20:4ω6, C20:5ω3 (EPA), C22:5ω3 (DPA) and C22:6ω3 (DHA). These results suggest: (i) the vital importance of the conservation of C20:4ω6 as a precursor of eicosanoids; (ii) the retention of EPA, DPA and DHA for metabolic energy for reproduction; and (iii) the utilization of C18:1ω9 for metabolic fuel use in the beginning of the spawning period. Hepatic lipolysis and lipogenesis revealed significant differences which could, eventually, result from the diet during the parasitic phase of sea lamprey life cycle. Present results revealed that the muscle act as a fat depot site which explains the few significant correlations observed for fatty acids between muscle and liver. Muscle neutral lipids fatty acid signature at the beginning of the spawning migration can be used to distinguish differences in the diet of sea lampreys during the marine trophic phase of their life cycle.     

Essential role of docosahexaenoic acid towards development of a smarter brain

Evolution of the high order brain function in humans can be attributed to intake of poly unsaturated fatty acids (PUFAs) of which the ω-3 fatty acid, docosahexaenoic acid (DHA) has special significance. DHA is abundantly present in the human brain and is an essential requirement in every step of brain development like neural cell proliferation, migration, differentiation, synaptogenesis etc. The multiple double bonds and unique structure allow DHA to impart special membrane characteristics for effective cell signaling. Evidences indicate that DHA accumulate in areas of the brain associated with learning and memory. Many development disorders like dyslexia, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia etc. are causally related to decreased level of DHA. The review discusses the various reports of DHA in these areas for a better understanding of the role of DHA in overall brain development. Studies involving laboratory animals and clinical findings in cases as well as during trials have been taken into consideration. Additionally the currently available dietary source of DHA for supplementation as nutraceutics with general caution for overuse has been examined.     

Shallow hypothermia depends on the level of fatty acid unsaturation in adipose and liver tissues in a tropical heterothermic primate

Optimal levels of unsaturated fatty acids have positive impacts on the use of prolonged bouts of hypothermia in mammalian hibernators, which generally have to face low winter ambient temperatures. Unsaturated fatty acids can maintain the fluidity of fat and membrane phospholipids at low body temperatures. However, less attention has been paid to their role in the regulation of shallow hypothermia, and in tropical species, which may be challenged more by seasonal energetic and/or water shortages than by low temperatures. The present study assessed the relationship between the fatty acids content of white adipose and liver tissues and the expression of shallow hypothermia in a tropical heterothermic primate, the gray mouse lemur (Microcebus murinus). The adipose tissue is the main tissue for fat storage and the liver is involved in lipid metabolism, so both tissues were expected to influence hypothermia dependence on fatty acids. As mouse lemurs largely avoid deep hypothermia (i.e. torpor) use under standard captive conditions, the expression of hypothermia was triggered by food-restricting experimental animals. Hypothermia depth increased with time, with a stronger increase for individuals that exhibited higher contents of unsaturated fatty acids suggesting that they were more flexible in their use of hypothermia. However these same animals delayed the use of long hypothermia bouts relative to individuals with a higher level of saturated fatty acids. This study evidences for the first time that body fatty acids unsaturation levels influence the regulation of body temperature not only in cold-exposed hibernators but also in tropical, facultative heterotherms.     

Membrane lipids of a psychrophilic and barophilic deep-sea bacterium

In a psychrophilic and barophilic marine bacterial isolate of the genusAlteromonas, the ratio of total unsaturated versus saturated fatty acids in the membrane lipids increased when the organism was grown at increasing hydrostatic pressures and decreasing temperatures. This regulatory capacity, as well as the presence of relatively large amounts of 20:5 polyunsaturated fatty acid, appear to be functional in maintaining membrane fluidity within a range of pressures distinctly below and above the specific optimum and at typical deep sea temperatures.     

Observations of neutral buoyancy in diapausing copepods Calanoides acutus during Antarctic winter

The herbivorous Antarctic copepod Calanoides acutus overwinters inactively in a resting stage (diapause) at depths below 500 m. It is assumed that during diapause C. acutus is neutrally buoyant in order to retain energy reserves otherwise depleted by swimming activities. However, so far, no experimental observations on its buoyancy have been reported and our knowledge of buoyancy regulation mechanisms is incomplete. In the present study, species-specific differences in buoyancy were assessed visually. Observations were made of specimens from the diapausing cohort of C. acutus and compared to another herbivorous copepod Calanus propinquus, which overwinters actively feeding in the upper water layers. Freshly caught copepods were anaesthetized in a 3-amino-benzoic acid ethyl ester (MS222) in seawater solution in order to exclude the influence of swimming movements on buoyancy control. It was shown that C. propinquus was negatively buoyant, whereas diapausing C. acutus remained neutrally buoyant. This is the first record that neutral buoyancy in diapausing copepods is maintained by the biochemical body composition without the additional need of swimming movements.     

用基因工程方法研制廿二碳六烯酸

廿二碳六烯酸(DHA)能促进脑细胞的生长发育,改善大脑机能和行为学习,防治中枢神经疾病,是人及其它动物重要的必需多不饱和脂肪酸。目前,DHA主要来自深海鱼油的分离制备。利用微生物发酵生产DHA仍处于实验室阶段。破囊壶菌(Thraustochytriumroseum)是合成DHA的优良海洋真菌。研究与筛选破囊壶菌DHA合成突变株,克隆破囊壶菌DHA合成关键酶基因,进而在酵母真核表达系统中表达,可为今后对该酶进行更深入的研究及应用建立良好的基础。用基因工程方法研制重组DHA,将开拓广阔的应用前景。     

Changes in fluidity and 22:6(n − 3) content in phospholipids of trout intestinal brush-border membrane as related to environmental salinity

Phospholipids and fatty acids analyses were carried out on brush-border membranes isolated from trout intestine. Phosphatidylcholine (PC) is the principal phospholipid of these membranes. When animals are transferred from fresh water to sea water, the content of the 22:6(n ? 3) fatty acid strongly increases at the level of phospholipids, mainly PC. Concomitantly, an important increase in the fluidity of the lipid core of the membrane was detected by steady-state fluorescence anisotropy. It is suggested that the molecular species of PC (especially rich in n ? 3 fatty acids) may have an important part to play in marine organisms according to the osmoregulation problems met in these animals.     

Seasonal and spatial shifts in copepod diets within tropical estuaries measured by fatty acid profiles

Fatty acids are the main components of lipids and are necessary for the production and permeability of cell membranes, playing an essential role in the physiological responses of organisms. The biochemical composition of zooplankton might be used as bio-indicators of the trophic status of aquatic ecosystems. Aiming to fill the gap of knowledge in tropical estuaries, the main aim of this study was to test if the fatty acid profiles can reveal spatial and temporal shifts in the diet of copepods and therefore can be used as indicators of the trophic status of estuarine systems. We investigated the fatty acids composition of copepod species and their possible food sources along the salinity gradient of two tropical estuaries (Paraíba do Norte and Mamanguape estuaries, northeastern Brazil), during the rainy and dry seasons. We found clear seasonal differences regarding fatty acids composition and concentration in copepods, with maximal concentrations and diversity of total fatty acids during the rainy season. The copepods species were mainly carnivorous in the dry season and omnivorous in the rainy season and, in both estuaries, the diet of most copepods was dependent on food availability. The fatty acid profiles suggest that, in general, feeding patterns of zooplankton change spatially and temporally, reflecting the shifts in their food sources abundance (i.e., dominance among diatoms and flagellates, terrestrial detritus and small animals). We observed a residual proportion of terrestrial detritus and green algae in the diets and these items were only present in the dry season. Furthermore, the food sources in the Paraiba do Norte estuary, a system with high levels of anthropogenic disturbance, showed lower feeding quality, with lower essential fatty acids concentrations. Our study showed that fatty acid profiles can be used as ecological indicator to assess seasonal and spatial shifts in the trophic ecology of copepods in tropical estuaries and to distinguish systems with different levels of human impact in a fast and accurate way.     

Effect of varying levels of dietary essential fatty acid during early ontogeny of the sea scallop Placopecten magellanicus

This study investigated the biological effects of various dietary essential fatty acids levels to sea scallop larvae, Placopecten magellanicus. Scallop larvae were fed three diets from D-veliger to settlement. Diet A consisted of Isochrysis sp. and Pavlova lutheri, diet B was a mix of Isochrysis sp. and Chaetoceros muelleri and diet C consisted of the same two species, but C. muelleri was grown under silicate deprivation to alter the fatty acid composition. Pediveligers (28 days old) were sampled prior to settlement for fatty acid analysis, growth measurement and survival assessment. Survival and settlement success were measured at the end of the experiment (day 40). Our results show that feeding regime greatly influenced larval size, settlement and fatty acid composition. Diet A was severely deficient in arachidonic acid (20:4n-6, AA), leading to the poorest larval growth, survival and lipid content. Nevertheless, larvae fed diet A selectively accumulate AA by a factor three compared to the dietary amount. Shell size of 28-day-old larvae was positively correlated with AA content and negatively correlated with eicosapentaenoic acid (20:5n-3, EPA)-AA ratio, thus suggesting that these two variables are of major interest for the optimisation of larval growth in sea scallops. Finally, larvae fed diet C displayed 20% higher shell size at day 28 than larvae fed diet A and B, likely in relation to the dietary amount of saturated fatty acid (SFA). However, the moderate survival and settlement success of these groups of larvae might be associated with a relative deficiency in docosahexaenoic acid (22:6n-3, DHA). This study underlines that the overall balance between polyunsaturated fatty acid (PUFA) needs to be considered to adequately fed sea scallop larvae.     

N-3 fatty acids and membrane microdomains: From model membranes to lymphocyte function

This article summarizes the author's research on fish oil derived n-3 fatty acids, plasma membrane organization and B cell function. We first cover basic model membrane studies that investigated how docosahexaenoic acid (DHA) targeted the organization of sphingolipid-cholesterol enriched lipid microdomains. A key finding here was that DHA had a relatively poor affinity for cholesterol. This work led to a model that predicted DHA acyl chains in cells would manipulate lipid-protein microdomain organization and thereby function. We then review how the predictions of the model were tested with B cells in vitro followed by experiments using mice fed fish oil. These studies reveal a highly complex picture on how n-3 fatty acids target lipid-protein organization and B cell function. Key findings are as follows: (1) n-3 fatty acids target not just the plasma membrane but also endomembrane organization; (2) DHA, but not eicosapentaenoic acid (EPA), disrupts microdomain spatial distribution (i.e. clustering), (3) DHA alters protein lateral organization and (4) changes in membrane organization are accompanied by functional effects on both innate and adaptive B cell function. Altogether, the research over the past 10 years has led to an evolution of the original model on how DHA reorganizes membrane microdomains. The work raises the intriguing possibility of testing the model at the human level to target health and disease.     

Changes of lipid content and fatty acid composition of Schizochytrium limacinum in response to different temperatures and salinities

The growth, lipid content and fatty acid composition of Schizochytrium limacinum OUC88 at different temperatures (16, 23, 30 and 37 °C) and salinities (0, 0.9, 1.8, 2.7 and 3.6%, w/v) were analyzed. The strain grew better and lipid contents were higher at 16–30 °C and salinity at 0.9–3.6% (w/v). The adaptive responses of this microbe to temperature and salinity were mainly to regulate the degree of fatty acid unstauration to maintain the normal membrane lipid physical state. However, at 37 °C and 0 salinity, the growth of the strain was inhibited obviously and the lipid content reduced significantly and, some important changes occurred in fatty acid composition, especially the odd-numbered fatty acids 15:0 and 17:0 which amounts increased greatly. In addition, the ratio of DHA to DPA changed at different temperatures and salinities.     

Dynamics of the Acinetobacter baumannii inner membrane under exogenous polyunsaturated fatty acid stress

Exogenous polyunsaturated fatty acids (PUFAs) are readily incorporated into the synthesis pathways of A. baumannii membrane phospholipids, where they contribute to reduced bacterial fitness and increased antimicrobial susceptibility. Here we examine the impact of PUFA membrane modification on membrane organisation and biophysical properties using coarse grained MARTINI simulations of chemically representative membrane models developed from mass-spectrometry datasets of an untreated, arachidonic acid (AA) treated and docosahexaenoic acid (DHA) treated A. baumannii membranes. Enzymatic integration of AA or DHA into phospholipids of the A. baumannii membrane resulted in modulation of membrane biophysical properties. Membrane thickness decreased slightly following PUFA treatment, concomitant with changes in the lateral area per lipid of each lipid headgroup class. PUFA treatment resulted in a decrease in membrane ordering and an increase in lipid lateral diffusion. Changes in lateral membrane organisation were observed in the PUFA treated membranes, with a concurrent increase in ordered cardiolipin domains and disordered PUFA-containing domains. Notably, separation between ordered and disordered domains was enhanced and was more pronounced for DHA relative to AA, providing a possible mechanism for greater antimicrobial action of DHA relative to AA observed experimentally. Furthermore, the membrane active antimicrobial, pentamidine, preferentially adsorbs to cardiolipin domains of the A. baumannii model membranes. This interaction, and membrane penetration of pentamidine, was enhanced following PUFA treatment. Cumulatively, this work explores the wide-ranging effects of PUFA incorporation on the A. baumannii membrane and provides a molecular basis for bacterial inner membrane disruption by PUFAs.