Bacterial Membrane Research Articles

Reaction-Induced Self-Assembly of Polymyxin Mitigates Cytotoxicity and Reverses Drug Resistance.

Polymyxins have been regarded as an efficient therapeutic against many life-threatening, multidrug resistant Gram-negative bacterial infections; however, the cytotoxicity and emergence of drug resistance associated with polymyxins have greatly hindered their clinical potential. Herein, the reaction-induced self-assembly (RISA) of polymyxins and natural aldehydes in aqueous solution is presented. The resulting assemblies effectively mask the positively charged nature of polymyxins, reducing their cytotoxicity. Moreover, the representative PMBA4 (composed of polymyxin B (PMB) and (E)-2-heptenal (A4)) assemblies demonstrate enhanced binding to Gram-negative bacterial outer membranes and exhibit multiple antimicrobial mechanisms, including increased membrane permeability, elevated bacterial metabolism, suppression of quorum sensing, reduced ATP synthesis, and potential reduction of bacterial drug resistance. Remarkably, PMBA4 assemblies reverse drug resistance in clinically isolated drug-resistant strains of Gram-negative bacteria, demonstrating exceptional efficacy in preventing and eradicating bacterial biofilms. PMBA4 assemblies efficiently eradicate Gram-negative bacterial biofilm infections in vivo and alleviate inflammatory response. This RISA strategy offers a practical and clinically applicable approach to minimize side effects, reverse drug resistance, and prevent the emergence of resistance associated with free polymyxins.

Exploring the molecular biology of zinc-doped hydroxyapatite nanocomposites as fillers for dental materials: a self-defensive approach targeting bacterial DNA

Abstract Infections during or after the denture filling pose a serious threat to recovery later, and antibiotics are scanty for quick healing. The antibacterial potential of Zn has convinced us to fabricate its composites with hydroxyapatite (HA), which has distinct biological properties. The main aim of the study is to evaluate the antibacterial potential of Zn-doped HA and investigate its molecular interaction with bacterial strains to enhance its defensive ability against bacterial attack. This study investigates the synthesis of zinc-doped hydroxyapatite nano-powder (Zn-HA) as coating and filling materials for dental applications. The co-precipitation technique was used in this regard to obtain the purest form of nanoparticles. The as-prepared Zn-HA samples were characterized by FTIR spectroscopy to assess the interaction of functional groups between components, X-ray diffraction (XRD) to determine percentage crystallinity, SEM to explore the surface morphology of composites, and EDX to confirm the incorporation of Zn in the apatite structure. The crystalline size of Zn-HA decreases from 99 nm to 40 nm with an increase in the doping of Zncl2 from 0 to 2.5g. With increasing the concentration of Zn doping, the effectiveness of antibacterial potential was increased. Due to an increased in the concentration of doped Zn, the Zn ions effectively rupture the bacterial membrane and destroy its DNA. Meanwhile, it shows the highest antibacterial activity against Pseudomonas (20.2±0.02), Klebsiella (25.8±0.05), Bacillus (18.3±0.09), S. aureus (24±0.03), and E. coli (19.3±0.09) with Zn/HA5.It showed that by increasing the concentration of Zinc ions in hydroxyapatite, the antibacterial potential increased. This increased concentration of zinc ions in HA enhances its-defensive ability against the attack of various bacterial strains, this makes it a potential material and enhances its efficacy in dental applications like coating, filling material, or dental restoratives, in inhibiting the growth of bacterial colonies and biofilm formation in the oral cavity. In this way, Zn/HA as an efficient dental composite as a restorative material with enhanced antibacterial potential may help to mitigate the risk of dental infections, promote dental as well as oral health, and overall improve the life of dentine.

Spatially structured exchange of metabolites enhances bacterial survival and resilience in biofilms

Biofilm formation enhances bacterial survival and antibiotic tolerance, but the underlying mechanisms are incompletely understood. Here, we show that biofilm growth is accompanied by a reduction in bacterial energy metabolism and membrane potential, together with metabolic exchanges between the inner and outer regions in biofilms. More specifically, nutrient-starved cells in the interior supply amino acids to cells in the periphery, while peripheral cells experience a decrease in membrane potential and provide fatty acids to interior cells. Fatty acids facilitate the repair of starvation-induced membrane damage in inner cells and enhance their survival in the presence of antibiotics. Thus, metabolic exchanges between inner and outer cells contribute to survival of the nutrient-starved inner cells and contribute to antibiotic tolerance within the biofilm.

Prototype of a biopolymer-based transdermal film with bacterial cellulose membrane and microneedles for methotrexate administration

This report presents a transdermal methotrexate (MTX) delivery system prototype using a bacterial cellulose (BC) matrix with microneedles (MN). The MTX-loaded BC layer (BC/MTX) was incorporated in microneedles. The BC/MTX/MN system was evaluated for structure, mechanical properties, cytotoxicity and in vitro drug release. After 24 h, 73% of MTX was released from BC. Cytotoxicity results showed 123% cell viability for BC and 111% for BC/MTX. These findings suggest the potential of the delivery system for releasing MTX in the treatment of dermatological diseases.

Helicity-directed recognition of bacterial phospholipid via radially amphiphilic antimicrobial peptides.

The fundamental differences in phospholipids between bacterial and mammalian cell membranes present remarkable opportunities for antimicrobial design. However, it is challenging to distinguish bacterial anionic phospholipid phosphatidylglycerol (PG) from mammalian anionic phosphatidylserine (PS) with the same net charge. Here, we report a class of radially amphiphilic α helix antimicrobial peptides (RAPs) that can selectively discriminate PG from PS, relying on the helix structure. The representative RAP, L10-MMBen, can direct the rearrangement of PG vesicles into a lamellar structure with its helix axis parallel to the PG membrane surface. The helical structure imparts both the thermodynamic and kinetic advantages of L10-MMBen/PG assembly, and the hiding of hydrophobic regions in RAPs is crucial for PG recognition. L10-MMBen exhibits high selectivity against bacteria depending on PG recognition, showing low in vivo toxicity and significant treatment efficacy in mice infection models. Our study introduces a helicity-direct bacterial phospholipid recognition paradigm for designing highly selective antimicrobial peptides.

Unraveling the treasure trove of phytochemicals in mitigating the Salmonella enterica infection.

Foodborne diseases triggered by various infectious micro-organisms are contributing significantly to the global disease burden as well as to increasing mortality rates. Salmonella enterica belongs to the most prevalent form of bacteria accountable for significant burden of foodborne illness across the globe. The conventional therapeutic approach to cater to Salmonella enterica-based infections relies on antibiotic therapy, but the rapid emergence of the antibiotic resistance strains of Salmonella sp. necessitates the development of alternative treatment and prevention strategies. In light of this growing concern, the scientific community is rigorously exploring novel phytochemicals harnessed from medicinally important plants as a promising approach to curb Salmonella enterica infections. A variety of phytochemicals belonging to alkaloids, phenols, flavonoid, and terpene classes are reported to exhibit their inhibitory activity against bacterial cell communication, membrane proteins, efflux pumps, and biofilm formation among drug resistant Salmonella strains. The present review article delves to discuss the emergence of antibiotic resistance among Salmonella enterica strains, various plant sources, identification of phytochemicals, and the current state of research on the use of phytochemicals as antimicrobial agents against Salmonella enterica, shedding light on the promising potential of phytochemicals in the fight against this pathogen.

Influence of surface texture: A comparative study on antibacterial activities of morphologically tailored zinc oxide

The morphology-dependent antibacterial activity of zinc oxide (ZnO) nanoparticles with three different morphologies, nanowall (NW), nanosphere (NS), and, nanorod (NR) was rigorously investigated to elucidate the influence of shape and size on their performance. Their morphological, surface, and structural characteristics were meticulously analyzed using SEM, BET, and XRD techniques. The antibacterial activity of synthesized ZnO samples was initially investigated and validated through in silico docking studies against nine bacterial strains, specifically targeting 1GCI, 2DCJ, 6KMM and 3T07, 6KVQ, 1MWT from gram-positive Bacillus sp. and Staphylococcus sp. respectively, 6N38, 6CRT, 6GRH from gram-negative E. coli. The docking simulations were performed using Autodock 4.2 software, yielding promising results characterized by negative binding energies, indicative of favorable interactions. The invitro studies were assessed against three same bacteria mentioned above using the disk diffusion method. The results demonstrated a pronounced dependency of antibacterial activity on the surface area, average crystallite size, and surface roughness of ZnO samples. ZnO (NW) exhibited markedly superior antibacterial properties. This enhanced efficacy is attributed to their higher surface area to volume ratio, smaller average crystallite size and increased surface roughness facilitating more efficient interactions with bacterial cell membranes. ZnO (NR) nanoparticles exhibited enhanced antibacterial activity despite minimal surface area.

Environmental Influence on Bacterial Lipid Composition: Insights from Pathogenic and Probiotic Strains.

The lipid composition of bacterial membranes is pivotal in regulating bacterial physiology, pathogenicity, and interactions with hosts. This study presents a comprehensive analysis of bacterial membrane lipid profiles across diverse Gram-positive and Gram-negative species. Utilizing matrix-assisted laser desorption/ionization (MALDI) in conjunction with advanced chemometric tools, we investigate the influence of environmental factors, isolation sources, and host metabolism on bacterial lipid profiles. Our findings unveil significant variations in lipid composition attributed to factors such as carbon/energy availability and exposure to chemicals, including antibiotics. Moreover, we identify distinct lipidomic signatures associated with pathogenic and probiotic bacterial strains, shedding light on their functional properties and metabolic pathways. Notably, bacterial strains isolated from clinical samples exhibit unique lipid profiles influenced by host metabolic dysregulation, particularly evident in conditions such as diabetic foot infections. These results deepen our understanding of the intricate mechanisms governing bacterial membrane lipid biology and hold promise for informing the development of innovative therapeutic and biotechnological strategies.

Enhancing frost-resistant and electrically conductive properties of bacterial cellulose-based IPN hydrogel wound dressings via photopolymerization: Towards epidermal sensor applications

Conventional wound dressings are limited in their application due to the difficulty of maintaining normal use in cold conditions and a lack of functionality. In this study, photopolymerization was employed to fabricate a wound dressing with the capacity to monitor vital signs in cold environments. Utilizing bacterial cellulose (BC) to form an Interpenetrating Network (IPN) structure, the dressing exhibits enhanced water retention and mechanical properties, with a notable increase in mechanical strength to 540.37 KPa. Moreover, it maintains excellent mechanical resilience and electrical conductivity (9.01 × 10−3 S/cm) even at temperatures as low as −20 ℃. Incorporation of positively charged quaternary ammonium salts imparts potent antibacterial properties to the hydrogel against Staphylococcus aureus and Escherichia coli by electrostatically adsorbing to and disrupting negatively charged bacterial cell membranes, resulting in the leakage of internal fluids. The efficacy of the hydrogel in promoting wound healing was validated through rat-infected wound models. Hematoxylin and eosin (H&E) staining confirmed a reduction in inflammation at the wound site, improved wound healing, and a marked increase in the wound healing rate. Moreover, the hydrogel has remarkable electrical conductivity (1.25 × 10−2 S/cm), enabling the detection of subtle signals (e.g., strain 0.25 %) crucial for emergency wound management to prevent infections. Of significant importance, these hydrogels can function as electrodes for monitoring electrocardiogram (ECG) signals and respiratory status, facilitating timely assessment of vital signs in casualties. This innovative hydrogel wound dressing holds promise for simultaneously monitoring human vital signs and treating wounds in cold outdoor settings, thus offering broad applications in the realms of wound management and dressing for cold outdoor sports.

Thermodynamic Details of Pinholin S2168 Activation Revealed Using Alchemical Free Energy Simulations.

Pinholin S2168 is a viral integral membrane protein whose function is to form nanoscopic "pinholes" in bacterial cell membranes to induce cell lysis as part of the viral replication cycle. Pinholin can transition from an inactive to an active conformation by exposing a transmembrane domain (TMD1) to the extracellular fluid. Upon activation, several copies of the protein assemble via interactions among a second transmembrane domain (TMD2) to form a single pore, thus hastening cell lysis and viral escape. The following experiments provide conformational descriptors of pinholin in active and inactive states and elucidate the molecular driving forces that control pinholin activity. In the present study, molecular dynamics (MD) simulations have been used to refine experimentally derived conformational descriptors into an atomistically detailed model of irsS2168, an antiholin mutant. To provide additional details about the thermodynamics of pinholin activation and to overcome large intrinsic kinetic barriers to activation, alchemical free energy simulations have been conducted. Alchemical mutations reveal the change in folding free energy upon mutation. The results suggest that alchemical mutations are an effective tool to rationalize experimental observations and predict the effects of site mutations on conformational states for proteins integrated into lipid bilayers. S16F, A17Q, A17Q+G21Q, and A17Q+G21Q+G14Q mutants reveal how changes in hydrophilicity and disruption of the glycine zipper motif influence pinholin's thermodynamic equilibrium, favoring the active conformation. These findings align with experimental observations from DEER spectroscopy, demonstrating that mutations increasing the hydrophilicity of TMD1 promote activation by making TMD1 more likely to exit the membrane and enter the extracellular fluid.

"Photo-Thermo-Electric" Dental Implant for Anti-Infection and Enhanced Osteoimmunomodulation.

The dental implant market has experienced explosive growth, owing to the widespread acceptance of implants as the core of oral rehabilitation. Clinically, achieving simultaneous anti-infective effects and rapid osseointegration is a crucial but challenging task for implants. The demand for implants with long-term broad-spectrum antibacterial and immune-osteogenic properties is growing. Existing methods are limited by a lack of safety, efficiency, short-lasting anti-infective ability, and inadequate consideration of the immunomodulatory effects on osteogenesis. Herein, a ZnO/black TiO2-x heterojunction surface structure was designed as a near-infrared (NIR) light-responsive nanofilm immobilized on a titanium (Ti) implant surface. This nanofilm introduces abundant oxygen vacancies and heterojunctions, which enhance the photothermal and photoelectric abilities of Ti implants under NIR illumination by narrowing the band gap and improving interfacial charge transfer. The "photo-thermo-electric" implant exhibits excellent broad-spectrum antibacterial efficacy against three dental pathogenic bacteria (Porphyromonas gingivalis, Fusobacterium nucleatum, and Staphylococcus aureus, >99.4%) by destroying the bacterial membrane and increasing the production of intracellular reactive oxygen species. Additionally, the implant can effectively eliminate mature multispecies biofilms and kill bacteria inside the biofilms under NIR irradiation. Meanwhile, this implant can also induce the pro-regenerative transformation of macrophages and promote osteoblast proliferation and differentiation. Moreover, in vivo results confirmed the superior antibacterial and osteoimmunomodulatory properties of this dental implant. RNA sequencing revealed that the underlying osteogenic mechanisms involve activation of the Wnt/β-catenin signaling pathway and bone development. Overall, this versatile "photo-thermo-electric" platform endows implants with anti-infection and bone integration performance simultaneously, which holds great potential for dental implants.

Combined release of LL37 peptide and zinc ion from a mussel-inspired coating on porous titanium for infected bone defect repairing

Implant-associated infections impose great burden on patient health and public healthcare. Antimicrobial peptides and metal ions are generally incorporated onto implant surface to deter bacteria colonization. However, it is still challenging to efficiently prevent postoperative infections at non-cytotoxic dosages. Herein, a scaffold based on porous titanium coated with a mussel-inspired dual-diameter TiO2 nanotubes is developed for loading dual drugs of LL37 peptide and Zn2+ with different sizes and characteristics. Benefiting from in-situ formed polydopamine layer and dual-diameter nanotubular structure, the scaffold provides an efficient platform for controllable drugs elution: accelerated release under acidic condition and sustained release for up to 28 days under neutral/alkalescent circumstances. Such combination of dual drugs simultaneously enhanced antibacterial efficacy and osteogenesis. In antibacterial test, LL37 peptide serving as bacteria membrane puncture agent, and Zn2+ acting as ROS generator, cooperatively destroyed bacterial membrane integrity and subsequently damaged bacterial DNA, endowing dual-drug loaded scaffold with remarkable bactericidal efficiency of > 92 % in vitro and > 99 % in vivo. Noteworthily, dual-drug loaded scaffold promoted bone-implant osteointegration under infectious microenvironment, overmatching single-drug load ones. It provides a promising strategy on surface modification of implant for infected bone defect repairing.

The Dual Mode of Antibacterial Action of the Synthetic Small Molecule DCAP Involves Lipid II Binding.

The synthetic small molecule DCAP is a chemically well-characterized compound with antibiotic activity against Gram-positive and Gram-negative bacteria, including drug-resistant pathogens. Until now, its mechanism of action was proposed to rely exclusively on targeting the bacterial membrane, thereby causing membrane depolarization, and increasing membrane permeability (Eun et al. 2012, J. Am. Chem. Soc. 134 (28), 11322-11325; Hurley et al. 2015, ACS Med. Chem. Lett. 6, 466-471). Here, we show that the antibiotic activity of DCAP results from a dual mode of action that is more targeted and multifaceted than previously anticipated. Using microbiological and biochemical assays in combination with fluorescence microscopy, we provide evidence that DCAP interacts with undecaprenyl pyrophosphate-coupled cell envelope precursors, thereby blocking peptidoglycan biosynthesis and impairing cell division site organization. Our work discloses a concise model for the mode of action of DCAP which involves the binding to a specific target molecule to exert pleiotropic effects on cell wall biosynthetic and divisome machineries.

The Sec pathway gene yidC regulates the virulence of mesophilic Aeromonassalmonicida

Aeromonas salmonicida is a common pathogenic bacterial species found in both freshwater and marine fish, leading to significant economic losses in the aquaculture industry. YidC is an accessory to SecYEG and is essential for the SecYEG transporter to insert into the bacterial membrane. However, the roles of the yidC gene on the host immune response remain unclear. Here, we compared the pathogenicity of yidC gene-deleted (ΔyidC) strain and wild-type (SRW-OG1) strain of mesophilic A. salmonicida to Orange-spotted grouper (Epinephelus coioides), and explored the impacts of yidC gene on the immune response of E. coioides to mesophilic A. salmonicida infection by using Red/ET recombineering. In this study, the E. coioides in the Secondary infected group had a 53.9 % higher survival rate than those in the Primary infected group. In addition, the adhesion ability of ΔyidC strain decreased by about 83.36 % compared with that of the wild-type (SRW-OG1) strain. Further comparison of the biological phenotype of SRW-OG1 and ΔyidC revealed that this yidC gene could regulate the expression of genes related to iron metabolism and have no effect on bacterial growth under the limited iron concentration. In the low concentration of Fe3+ and Fe2+ environment, SRW-OG1 can obtain iron ions by regulating yidC. Based on the above results, yidC gene contributed to the pathogenicity of mesophilic A. salmonicida to E. coioides, deletion of yidC gene promoted the inflammation and immune response of E. coioides to mesophilic A. salmonicida infection.

Copper doped carbon dots modified bacterial cellulose with enhanced antibacterial and immune regulatory functions for accelerating wound healing

The microenvironment of wound healing is susceptible to bacterial infection, chronic inflammation, oxidative stress, and inadequate angiogenesis, requiring the development of innovative wound dressings with antibacterial, anti-inflammatory, antioxidant, and angiogenic capabilities. This research crafted a new multifunctional bacterial cellulose composite membrane infused with copper-doped carbon dots (BC/Cu(II)-RCDs). Findings validated the successful loading of copper-doped carbon dots onto the BC membrane via hydrogen bonding interactions. Compared to the pure BC membrane, the BC/Cu(II)-RCDs composite membrane exhibited significantly enhanced hydrophilicity, tensile properties, and thermal stability. Diverse in vitro assays demonstrated excellent biocompatibility and antibacterial activity of BC/Cu(II)-RCDs composite membranes, alongside their ability to expedite the inflammatory phase and stimulate angiogenesis. In vivo trials corroborated the membrane's ability to foster epithelial regeneration, collagen deposition, and tissue regrowth in full-thickness skin wounds in rats while also curbing inflammation in infected full-thickness skin wounds. More importantly, the treatment of the BC/Cu(II)-RCDs composite membrane may result in the activation of VEGF and MAPK signaling proteins, which are key players in cell migration, angiogenesis, and skin tissue development. In essence, the developed BC/Cu(II)-RCDs composite membrane shows promise for treating infected wounds and serves as a viable alternative material for medicinal bandages.

Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides

Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Antibacterial Activity and Cytotoxicity of the Novel Bacteriocin Pkmh.

Bacteriocins are a class of proteins produced by bacteria that are toxic to other bacteria. These bacteriocins play a role in bacterial competition by helping to inhibit potential competitors. In this study, we isolated and purified a novel bacteriocin Pkmh, different from the previously reported bacteriocin PA166, from Pseudomonas sp. strain 166 by ammonium sulfate precipitation, dialysis membrane method, ion exchange chromatography, and gel filtration chromatography. SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) revealed that the molecular weight of Pkmh is approximately 35 kDa. Pkmh exhibited potent antimicrobial activity against bovine Mannheimia haemolytica (M. haemolytica) with low cytotoxicity, and lower hemolytic activity was observed. In addition, Pkmh retained antimicrobial activity at different pH ranges (2-10) and temperature conditions (40, 60, 80, 100 °C). Our analysis of its antimicrobial mechanism showed that Pkmh acts on bacterial cell membranes, increasing their permeability and leading to cell membrane rupture and death. In conclusion, Pkmh exhibited low hemolytic activity, low toxicity, and potent antibacterial effects, suggesting its potential as a promising candidate for clinical therapeutic drugs.

Photocatalytic Ag-MOF confers efficient antimicrobial activity to modified polyvinyl alcohol films

Antimicrobial packaging films are an effective means to avoid food infections. PVA has good film-forming and mechanical properties, but its water resistance and antimicrobial properties are insufficient. In this study, a rod-shaped Ag-MOF with photocatalytic properties was synthesized as an antimicrobial agent by a hydrothermal method using citrate esterified PVA as a film-forming substrate. The MICs of Ag-MOF against Escherichia coli and Staphylococcus aureus were 16 μg/mL and 32 μg/mL, respectively, and it had good biocompatibility. Under blue light irradiation, Ag-MOF induced the production of ROS, which increased the inhibition rate by more than 83.78%. The antimicrobial mechanism experiments showed that it caused irreversible damage to the bacterial cell membrane through the synergistic effect of Ag+ and ROS. The best mechanical properties of the films were obtained at 3% citric acid content, with the water vapor transmission rate, water solubility and swelling rate reduced by 0.19 g·mm·m−2·h−1·kPa−1, 65.33% and 11.26%, respectively. The antimicrobial rate of the composite film could reach more than 98% by adding only 1 MIC of Ag-MOF. In conclusion, photocatalytic antimicrobial agents have great potential for application in food packaging.

Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities.

Peptides that form transmembrane barrel-stave pores are potential alternative therapeutics for bacterial infections and cancer. However, their optimization for clinical translation is hampered by a lack of sequence-function understanding. Recently, we have de novo designed the first synthetic barrel-stave pore-forming antimicrobial peptide with an identified function of all residues. Here, we systematically mutate the peptide to improve pore-forming ability in anticipation of enhanced activity. Using computer simulations, supported by liposome leakage and atomic force microscopy experiments, we find that pore-forming ability, while critical, is not the limiting factor for improving activity in the submicromolar range. Affinity for bacterial and cancer cell membranes needs to be optimized simultaneously. Optimized peptides more effectively killed antibiotic-resistant ESKAPEE bacteria at submicromolar concentrations, showing low cytotoxicity to human cells and skin model. Peptides showed systemic anti-infective activity in a preclinical mouse model of Acinetobacter baumannii infection. We also demonstrate peptide optimization for pH-dependent antimicrobial and anticancer activity.

Bacterial outer membrane vesicles increase polymyxin resistance in Pseudomonas aeruginosa while inhibiting its quorum sensing

The persistent emergence of multidrug-resistant bacterial pathogens is leading to a decline in the therapeutic efficacy of antibiotics, with Pseudomonas aeruginosa (P. aeruginosa) emerging as a notable threat. We investigated the antibiotic resistance and quorum sensing (QS) system of P. aeruginosa, with a particular focused on outer membrane vesicles (OMVs) and polymyxin B as the last line of antibiotic defense. Our findings indicate that OMVs increase the resistance of P. aeruginosa to polymyxin B. The overall gene transcription levels within P. aeruginosa also reveal that OMVs can reduce the efficacy of polymyxin B. However, both OMVs and sublethal concentrations of polymyxin B suppressed the transcription levels of genes associated with the QS system. Furthermore, OMVs and polymyxin B acted in concert on the QS system of P. aeruginosa to produce a more potent inhibitory effect. This suppression was evidenced by a decrease in the secretion of virulence factors, impaired bacterial motility, and a notable decline in the ability to form biofilms. These results reveal that OMVs enhance the resistance of P. aeruginosa to polymyxin B, yet they collaborate with polymyxin B to inhibit the QS system. Our research contribute to a deeper understanding of the resistance mechanisms of P. aeruginosa in the environment, and provide new insights into the reduction of bacterial infections caused by P. aeruginosa through the QS system.