# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 5182 | 0 | 0.9874 | Evaluating virulence features of Acinetobacter baumannii resistant to polymyxin B. The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI, and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared with Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI, and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets. | 2024 | 38942450 |
| 6369 | 1 | 0.9873 | Association of furanone C-30 with biofilm formation & antibiotic resistance in Pseudomonas aeruginosa. BACKGROUND & OBJECTIVES: Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial bloodstream infections in humans. This study was aimed to explore the association of furanone C-30 with biofilm formation, quorum sensing (QS) system and antibiotic resistance in P. aeruginosa. METHODS: An in vitro model of P. aeruginosa bacterial biofilm was established using the standard P. aeruginosa strain (PAO-1). After treatment with 2.5 and 5 μg/ml of furanone C-30, the change of biofilm morphology of PAO-1 was observed, and the expression levels of QS-regulated virulence genes (lasB, rhlA and phzA2), QS receptor genes (lasR, rhlR and pqsR) as well as QS signal molecule synthase genes (lasI, rhlI, pqsE and pqsH) were determined. Besides, the AmpC expression was quantified in planktonic and mature biofilm induced by antibiotics. RESULTS: Furanone C-30 treatment significantly inhibited biofilm formation in a dose-dependent manner. With the increase of furanone C-30 concentration, the expression levels of lasB, rhlA, phzA2, pqsR, lasI, rhlI pqsE and pqsH significantly decreased in mature biofilm bacteria while the expression levels of lasR and rhlR markedly increased. The AmpC expression was significantly decreased in both planktonic and biofilm bacteria induced by imipenem and ceftazidime. INTERPRETATION & CONCLUSIONS: Furanone C-30 may inhibit biofilm formation and antibiotic resistance in P. aeruginosa through regulating QS genes. The inhibitory effect of furanone C-30 on las system appeared to be stronger than that on rhl system. Further studies need to be done with different strains of P. aeruginosa to confirm our findings. | 2018 | 29998876 |
| 9053 | 2 | 0.9873 | Nordihydroguaiaretic acid reverses the antibacterial activity of colistin against MCR-1-positive bacteria in vivo/in vitro by inhibiting MCR-1 activity and injuring the bacterial cell membrane. BACKGROUND: Colistin (polymyxin E) is an effective antibiotic for the treatment of most multidrug-resistant Gram-negative bacteria. However, some bacteria, including bacterial spp. belonging to the Enterobacteriaceae family, have an acquired resistance against polymyxins, which is attributed to they possess plasmid-carried resistance genes (mcr-1 and its variants). So, there is an urgent need to develop new therapeutic strategies to target broad spectrum resistant spp. from Enterobacteriaceae family in response to the loss of the protective barrier of last-line antibiotics. Here, we report the adjuvant capacity of nordihydroguaiaretic acid (NDGA) for restoring the antibacterial activity of colistin against MCR-1-positive E. coli ZJ487 in vivo/in vitro. METHODS: A checkerboard assay, time-killing analysis, isobolograms, growth curves and inducible resistance test showed the effect of NDGA combined with colistin in vitro. TLC was used to detect the inhibitory effect of NDGA on MCR-1. Colony determination and hematoxylin and eosin (HE) staining were used to assess the synergistic effect of NDGA and colistin in mice. RESULTS: Our results showed that NDGA in combination with colistin showed a synergistic bactericidal action without inducing resistance. NDGA directly inhibited MCR-1 activity and resulted in measurable injury to the bacterial cell membrane to recover the antibacterial effect of colistin. Most importantly, NDGA in combination with colistin exhibited an in vivo synergistic effect in murine peritonitis infection models, as evidenced by the survival rate of MCR-1-positive E. coli ZJ487-infected mice which increased from 6.67 to 50.0%. CONCLUSION: Our study demonstrated that NDGA effectively rescues the efficiency of colistin against MCR-positive E. coli ZJ487 by simultaneously inhibiting both, the MCR activity and the injury to the cell membrane of bacteria. | 2022 | 35158237 |
| 6224 | 3 | 0.9872 | Bacteriophage-resistant Staphylococcus aureus mutant confers broad immunity against staphylococcal infection in mice. In the presence of a bacteriophage (a bacteria-attacking virus) resistance is clearly beneficial to the bacteria. As expected in such conditions, resistant bacteria emerge rapidly. However, in the absence of the phage, resistant bacteria often display reduced fitness, compared to their sensitive counterparts. The present study explored the fitness cost associated with phage-resistance as an opportunity to isolate an attenuated strain of S. aureus. The phage-resistant strain A172 was isolated from the phage-sensitive strain A170 in the presence of the M(Sa) phage. Acquisition of phage-resistance altered several properties of A172, causing reduced growth rate, under-expression of numerous genes and production of capsular polysaccharide. In vivo, A172 modulated the transcription of the TNF-alpha, IFN-gamma and Il-1beta genes and, given intramuscularly, protected mice from a lethal dose of A170 (18/20). The heat-killed vaccine also afforded protection from heterologous methicillin-resistant S. aureus (MRSA) (8/10 mice) or vancomycin-intermediate S. aureus (VISA) (9/10 mice). The same vaccine was also effective when administered as an aerosol. Anti-A172 mouse antibodies, in the dose of 10 microl/mouse, protected the animals (10/10, in two independent experiments) from a lethal dose of A170. Consisting predominantly of the sugars glucose and galactose, the capsular polysaccharide of A172, given in the dose of 25 microg/mouse, also protected the mice (20/20) from a lethal dose of A170. The above results demonstrate that selection for phage-resistance can facilitate bacterial vaccine preparation. | 2010 | 20661301 |
| 5063 | 4 | 0.9870 | Antibiotic resistance ofKlebsiella pneumoniae through β-arrestin recruitment-induced β-lactamase signaling pathway. Overuse and misuse of antibiotics leads to rapid evolution of antibiotic-resistant bacteria and antibiotic resistance genes. Klebsiella pneumoniae has become the most common pathogenic bacterium accountable for nosocomial infections due to its high virulence factor and general occurrence of resistance to most antibiotics. The β-lactamase signaling pathway has been suggested to be involved in antibiotic resistance against β-lactams in Klebsiella pneumoniae. In the present study, the molecular mechanism of the antibiotic resistance of Klebsiella pneumoniae was investigated and the results indicated involvement of the β-arrestin recruitment-induced β-lactamase signaling pathway. Antimicrobial susceptibility of Klebsiella pneumoniae was assessed using automated systems and extended-spectrum β-lactamase (ESBL) and β-arrestin expression levels in Klebsiella pneumoniae were analyzed by reverse-transcription quantitative PCR. β-lactam resistance in Klebsiella pneumoniae was determined using β-lactam agar screening plates. The results demonstrated that β-arrestin recruitment was increased in Klebsiella pneumoniae with antibiotic resistance (AR-K.P.) compared with that in the native Klebsiella pneumoniae strain (NB-K.P.). Increased production of ESBL was observed in AR-K.P. after treatment with the β-lactam penicillin. Of note, inhibition of β-arrestin recruitment significantly suppressed ESBL expression in AR-K.P. and in addition, genes encoding β-arrestin and ESBL were upregulated in Klebsiella pneumoniae. Restoration of endogenous β-arrestin markedly increased antibiotic resistance of Klebsiella pneumoniae to β-lactam. Knockdown of endogenous β-arrestin downregulated antibiotic resistance genes and promoted the inhibitory effects of β-lactam antibiotic treatment on Klebsiella pneumoniae growth. In conclusion, the present study identified that β-arrestin recruitment was associated with growth and resistance to β-lactams, which suggested that β-arrestin regulating ESBL expression may be a potential target for addressing antibiotic resistance to β-lactams in Klebsiella pneumoniae. | 2018 | 29563975 |
| 8874 | 5 | 0.9869 | KatG and KatE confer Acinetobacter resistance to hydrogen peroxide but sensitize bacteria to killing by phagocytic respiratory burst. AIMS: Catalase catalyzes the degradation of H2O2. Acinetobacter species have four predicted catalase genes, katA, katE, katG, and katX. The aims of the present study seek to determine which catalase(s) plays a predominant role in determining the resistance to H2O2, and to assess the role of catalase in Acinetobacter virulence. MAIN METHODS: Mutants of Acinetobacter baumannii and Acinetobacter nosocomialis with deficiencies in katA, katE, katG, and katX were tested for sensitivity to H2O2, either by halo assays or by liquid culture assays. Respiratory burst of neutrophils, in response to A. nosocomialis, was assessed by chemiluminescence to examine the effects of catalase on the production of reactive oxygen species (ROS) in neutrophils. Bacterial virulence was assessed using a Galleria mellonella larva infection model. KEY FINDINGS: The capacities of A. baumannii and A. nosocomialis to degrade H2O2 are largely dependent on katE. The resistance of both A. baumannii and A. nosocomialis to H2O2 is primarily determined by the katG gene, although katE also plays a minor role in H2O2 resistance. Bacteria lacking both the katG and katE genes exhibit the highest sensitivity to H2O2. While A. nosocomialis bacteria with katE and/or katG were able to decrease ROS production by neutrophils, these cells also induced a more robust respiratory burst in neutrophils than did cells deficient in both katE and katG. We also found that A. nosocomialis deficient in both katE and katG was more virulent than the wildtype A. nosocomialis strain. SIGNIFICANCE: Our findings suggest that inhibition of Acinetobacter catalase may help to overcome the resistance of Acinetobacter species to microbicidal H2O2 and facilitate bacterial disinfection. | 2016 | 26860891 |
| 9054 | 6 | 0.9869 | Clinically Relevant Concentrations of Polymyxin B and Meropenem Synergistically Kill Multidrug-Resistant Pseudomonas aeruginosa and Minimize Biofilm Formation. The emergence of antibiotic resistance has severely impaired the treatment of chronic respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Since the reintroduction of polymyxins as a last-line therapy against MDR Gram-negative bacteria, resistance to its monotherapy and recurrent infections continue to be reported and synergistic antibiotic combinations have been investigated. In this study, comprehensive in vitro microbiological evaluations including synergy panel screening, population analysis profiling, time-kill kinetics, anti-biofilm formation and membrane damage analysis studies were conducted to evaluate the combination of polymyxin B and meropenem against biofilm-producing, polymyxin-resistant MDR P. aeruginosa. Two phylogenetically unrelated MDR P. aeruginosa strains, FADDI-PA060 (MIC of polymyxin B [MIC(polymyxin B)], 64 mg/L; MIC(meropenem), 64 mg/L) and FADDI-PA107 (MIC(polymyxin B), 32 mg/L; MIC(meropenem), 4 mg/L) were investigated. Genome sequencing identified 57 (FADDI-PA060) and 50 (FADDI-PA107) genes predicted to confer resistance to a variety of antimicrobials, as well as multiple virulence factors in each strain. The presence of resistance genes to a particular antibiotic class generally aligned with MIC results. For both strains, all monotherapies of polymyxin B failed with substantial regrowth and biofilm formation. The combination of polymyxin B (16 mg/L)/meropenem (16 mg/L) was most effective, enhancing initial bacterial killing of FADDI-PA060 by ~3 log(10) CFU/mL, followed by a prolonged inhibition of regrowth for up to 24 h with a significant reduction in biofilm formation (* p < 0.05). Membrane integrity studies revealed a substantial increase in membrane depolarization and membrane permeability in the surviving cells. Against FADDI-PA107, planktonic and biofilm bacteria were completely eradicated. In summary, the combination of polymyxin B and meropenem demonstrated synergistic bacterial killing while reinstating the efficacy of two previously ineffective antibiotics against difficult-to-treat polymyxin-resistant MDR P. aeruginosa. | 2021 | 33918040 |
| 8784 | 7 | 0.9869 | Bacillus firmus Strain I-1582, a Nematode Antagonist by Itself and Through the Plant. Bacillus firmus I-1582 is approved in Europe for the management of Meloidogyne on vegetable crops. However, little information about its modes of action and temperature requirements is available, despite the effect of these parameters in its efficacy. The cardinal temperatures for bacterial growth and biofilm formation were determined. The bacteria was transformed with GFP to study its effect on nematode eggs and root colonization of tomato (Solanum lycopersicum) and cucumber (Cucumis sativus) by laser-scanning confocal microscopy. Induction of plant resistance was determined in split-root experiments and the dynamic regulation of genes related to jasmonic acid (JA) and salicylic acid (SA) by RT-qPCR at three different times after nematode inoculation. The bacteria was able to grow and form biofilms between 15 and 45°C; it degraded egg-shells and colonized eggs; it colonized tomato roots more extensively than cucumber roots; it induced systemic resistance in tomato, but not in cucumber; SA and JA related genes were primed at different times after nematode inoculation in tomato, but only the SA-related gene was up-regulated at 7 days after nematode inoculation in cucumber. In conclusion, B. firmus I-1582 is active at a wide range of temperatures; its optimal growth temperature is 35°C; it is able to degrade Meloidogyne eggs, and to colonize plant roots, inducing systemic resistance in a plant dependent species manner. | 2020 | 32765537 |
| 8194 | 8 | 0.9868 | Role of the phenazine-inducing protein Pip in stress resistance of Pseudomonas chlororaphis. The triggering of antibiotic production by various environmental stress molecules can be interpreted as bacteria's response to obtain increased fitness to putative danger, whereas the opposite situation - inhibition of antibiotic production - is more complicated to understand. Phenazines enable Pseudomonas species to eliminate competitors for rhizosphere colonization and are typical virulence factors used for model studies. In the present work, we have investigated the negative effect of subinhibitory concentrations of NaCl, fusaric acid and two antibiotics on quorum-sensing-controlled phenazine production by Pseudomonas chlororaphis. The selected stress factors inhibit phenazine synthesis despite sufficient cell density. Subsequently, we have identified connections between known genes of the phenazine-inducing cascade, including PsrA (Pseudomonas sigma regulator), RpoS (alternative sigma factor), Pip (phenazine inducing protein) and PhzI/PhzR (quorum-sensing system). Under all tested conditions, overexpression of Pip or PhzR restored phenazine production while overexpression of PsrA or RpoS did not. This forced restoration of phenazine production in strains overexpressing regulatory genes pip and phzR significantly impairs growth and stress resistance; this is particularly severe with pip overexpression. We suggest a novel physiological explanation for the inhibition of phenazine virulence factors in pseudomonas species responding to toxic compounds. We propose that switching off phenazine-1-carboxamide (PCN) synthesis by attenuating pip expression would favour processes required for survival. In our model, this 'decision' point for promoting PCN production or stress resistance is located downstream of rpoS and just above pip. However, a test with the stress factor rifampicin shows no significant inhibition of Pip production, suggesting that stress factors may also target other and so far unknown protagonists of the PCN signalling cascade. | 2011 | 21030433 |
| 38 | 9 | 0.9868 | Alginate Oligosaccharide (AOS) induced resistance to Pst DC3000 via salicylic acid-mediated signaling pathway in Arabidopsis thaliana. Alginate Oligosaccharide (AOS) is a natural biological carbohydrate extracted from seaweed. In our study, Arabidopsis thaliana was used to evaluate the AOS-induced resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Resistance was vitally enhanced at 25 mg/L in wild type (WT), showing the decreased disease index and bacteria colonies, burst of ROS and NO, high transcription expression of resistance genes PR1 and increased content of salicylic acid (SA). In SA deficient mutant (sid2), AOS-induced disease resistance dropped obviously compared to WT. The disease index was significantly higher than WT and the expression of recA and avrPtoB are two and four times lower than WT, implying that AOS induces disease resistance injecting Pst DC3000 after three days treatment by arousing the SA pathway. Our results provide a reference for the profound research and application of AOS in agriculture. | 2019 | 31521273 |
| 9768 | 10 | 0.9868 | Inosine monophosphate overcomes the coexisting resistance of mcr-1 and bla(NDM-1) in Escherichia coli. INTRODUCTION: The rise of antibiotic-resistant bacteria, particularly those harboring mcr-1 and bla(NDM-1), threatens public health by reducing the efficacy of colistin and carbapenems. Recently, the co-spread of mcr-1 and bla(NDM-1) has been reported, and the emergence of dual-resistant Enterobacteriaceae severely exacerbates antimicrobial resistance. OBJECTIVES: This study aims to investigate the impact of mcr-1 and bla(NDM-1) expression on metabolism in Escherichia coli and to identify potential antimicrobial agents capable of overcoming the resistance conferred by these genes. METHODS: We employed non-targeted metabolomics to profile the metabolic perturbations of E. coli strains harboring mcr-1 and bla(NDM-1). The bactericidal effects of the differential metabolite, inosine monophosphate (IMP), were assessed both in vitro using time-killing assays and in vivo using a mouse infection model. The antimicrobial mechanism of IMP was elucidated through transcriptomic analysis and biochemical approaches. RESULTS: Metabolic profiling revealed significant alterations in the purine pathway, with IMP demonstrating potent bactericidal activity against E. coli strains carrying both resistance genes. IMP increased membrane permeability, disrupted proton motive force, reduced ATP levels, induced oxidative damage by promoting reactive oxygen species and inhibiting bacterial antioxidant defenses, and improved the survival rate of infected mice. CONCLUSION: Our findings suggest that IMP could be a promising candidate for combating mcr-1 and bla(NDM-1)-mediated resistance and provide a novel approach for discovering antimicrobial agents against colistin- and carbapenem-resistant bacteria. | 2025 | 40139526 |
| 6227 | 11 | 0.9867 | Lactoferrin Disaggregates Pneumococcal Biofilms and Inhibits Acquisition of Resistance Through Its DNase Activity. Streptococcus pneumoniae colonizes the upper airways of children and the elderly. Colonization progresses to persistent carriage when S. pneumoniae forms biofilms, a feature required for the development of pneumococcal disease. Nasopharyngeal biofilms are structured with a matrix that includes extracellular DNA (eDNA), which is sourced from the same pneumococci and other bacteria. This eDNA also allows pneumococci to acquire new traits, including antibiotic resistance genes. In this study, we investigated the efficacy of lactoferrin (LF), at physiological concentrations found in secretions with bactericidal activity [i.e., colostrum (100 μM), tears (25 μM)], in eradicating pneumococcal biofilms from human respiratory cells. The efficacy of synthetic LF-derived peptides was also assessed. We first demonstrated that LF inhibited colonization of S. pneumoniae on human respiratory cells without affecting the viability of planktonic bacteria. LF-derived peptides were, however, bactericidal for planktonic pneumococci but they did not affect viability of pre-formed biofilms. In contrast, LF (40 and 80 μM) eradicated pneumococcal biofilms that had been pre-formed on abiotic surfaces (i.e., polystyrene) and on human pharyngeal cells, as investigated by viable counts and confocal microscopy. LF also eradicated biofilms formed by S. pneumoniae strains with resistance to multiple antibiotics. We investigated whether treatment with LF would affect the biofilm structure by analyzing eDNA. Surprisingly, in pneumococcal biofilms treated with LF, the eDNA was absent in comparison to the untreated control (∼10 μg/ml) or those treated with LF-derived peptides. EMSA assays showed that LF binds S. pneumoniae DNA and a time-course study of DNA decay demonstrated that the DNA is degraded when bound by LF. This LF-associated DNase activity inhibited acquisition of antibiotic resistance genes in both in vitro transformation assays and in a life-like bioreactor system. In conclusion, we demonstrated that LF eradicates pneumococcal-colonizing biofilms at a concentration safe for humans and identified a LF-associated DNAse activity that inhibited the acquisition of resistance. | 2019 | 31681240 |
| 8809 | 12 | 0.9867 | Comparison of corrosion behaviour in presence of oral bacteria. The aim of this study was to compare the resistance of the corrosion of dental alloys in a solution containing oral bacteria named Actinomyces viscosus (ATCC19246). In this paper, we explain the choice of this precise species of bacteria, then specify its culture in artificial saliva and the experimental precautions needed to avoid the pollution by other bacteria. The electrochemical behaviour of two dental alloys (Ni-Cr alloy and gold-based alloy) was investigated by electrochemical means in sterile Fusayama artificial saliva (AS), AS enriched with sterile yeast extract (YE) and YE modified by introducing bacteria (AV). Open-circuit potentials, potentiodynamic curves, polarization resistance and impedance spectroscopy are the electrochemical procedures selected for this work. It has thus been shown that the open-circuit potential of the non-precious alloy is always lower than that of the gold precious alloy, and the colonization of metal surface by bacteria caused a drop in open circuit potential. The electrochemical impedance spectroscopy results have shown that the electrolyte resistance decreased between the AS, YE and AV milieu, in the presence of bacteria a slight decrease in polarization resistance was observed with the precious alloy and an increase with the non-precious alloy. The drop in the electrolyte resistance cannot explain the change in polarization resistance. The influence of Actinomyces viscosus might be essentially due to the consumption of oxygen at the metal/electrolyte interface of the specimen. For the non-precious alloy, the absence of oxygen (instigator of corrosion) led to an increase in polarization resistance whereas the slight decrease for the precious alloys might be justified by the organic and inorganic metabolites released by bacteria in to the electrolyte. The scanning electron micrography after electrochemical analysis, confirmed the absence of contaminants. These preliminary results demonstrate the unquestionable influence of this bacteria on the corrosion behaviour of the alloys studied, however, further studies are necessary. | 2001 | 11456067 |
| 6226 | 13 | 0.9867 | Chlorhexidine Promotes Psl Expression in Pseudomonas aeruginosa That Enhances Cell Aggregation with Preserved Pathogenicity Demonstrates an Adaptation against Antiseptic. Because Pseudomonas aeruginosa is frequently in contact with Chlorhexidine (a regular antiseptic), bacterial adaptations are possible. In comparison with the parent strain, the Chlorhexidine-adapted strain formed smaller colonies with metabolic downregulation (proteomic analysis) with the cross-resistance against colistin (an antibiotic for several antibiotic-resistant bacteria), partly through the modification of L-Ara4N in the lipopolysaccharide at the outer membrane. Chlorhexidine-adapted strain formed dense liquid-solid interface biofilms with enhanced cell aggregation partly due to the Chlorhexidine-induced overexpression of psl (exopolysaccharide-encoded gene) through the LadS/GacSA pathway (c-di-GMP-independence) in 12 h biofilms and maintained the aggregation with SiaD-mediated c-di-GMP dependence in 24 h biofilms as evaluated by polymerase chain reaction (PCR). The addition of Ca(2+) in the Chlorhexidine-adapted strain facilitated several Psl-associated genes, indicating an impact of Ca(2+) in Psl production. The activation by Chlorhexidine-treated sessile bacteria demonstrated a lower expression of IL-6 and IL-8 on fibroblasts and macrophages than the activation by the parent strain, indicating the less inflammatory reactions from Chlorhexidine-exposed bacteria. However, the 14-day severity of the wounds in mouse caused by Chlorhexidine-treated bacteria versus the parent strain was similar, as indicated by wound diameters and bacterial burdens. In conclusion, Chlorhexidine induced psl over-expression and colistin cross-resistance that might be clinically important. | 2022 | 35955437 |
| 6007 | 14 | 0.9867 | Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility. PURPOSE: Previously, we showed that tear fluid protects corneal epithelial cells against Pseudomonas aeruginosa without suppressing bacterial viability. Here, we studied how tear fluid affects bacterial gene expression. METHODS: RNA-sequencing was used to study the P. aeruginosa transcriptome after tear fluid exposure (5 h, 37 (o)C). Outcomes were further investigated by biochemical and physiological perturbations to tear fluid and tear-like fluid (TLF) and assessment of bacterial viability following tear/TLF pretreatment and antibiotic exposure. RESULTS: Tear fluid deregulated ~180 P. aeruginosa genes ≥8 fold versus PBS including downregulating lasI, rhlI, qscR (quorum sensing/virulence), oprH, phoP, phoQ (antimicrobial resistance) and arnBCADTEF (polymyxin B resistance). Upregulated genes included algF (biofilm formation) and hemO (iron acquisition). qPCR confirmed tear down-regulation of oprH, phoP and phoQ. Tear fluid pre-treatment increased P. aeruginosa resistance to meropenem ~5-fold (4 μg/ml), but enhanced polymyxin B susceptibility ~180-fold (1 μg/ml), the latter activity reduced by dilution in PBS. Media containing a subset of tear components (TLF) also sensitized bacteria to polymyxin B, but only ~22.5-fold, correlating with TLF/tear fluid Ca(2+) and Mg(2+) concentrations. Accordingly, phoQ mutants were not sensitized by TLF or tear fluid. Superior activity of tear fluid versus TLF against wild-type P. aeruginosa was heat resistant but proteinase K sensitive. CONCLUSION: P. aeruginosa responds to human tear fluid by upregulating genes associated with bacterial survival and adaptation. Meanwhile, tear fluid down-regulates multiple virulence-associated genes. Tears also utilize divalent cations and heat resistant/proteinase K sensitive component(s) to enhance P. aeruginosa sensitivity to polymyxin B. | 2021 | 34332149 |
| 9051 | 15 | 0.9867 | Chlorogenic acid inhibits virulence and resistance gene transfer in outer membrane vesicles of carbapenem-resistant Klebsiella pneumoniae. INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes. METHODS: We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms. RESULTS: This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection. DISCUSSION: These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection. | 2025 | 40230687 |
| 4769 | 16 | 0.9866 | Human breast milk isolated lactic acid bacteria: antimicrobial and immunomodulatory activity on the Galleria mellonella burn wound model. INTRODUCTION: Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic. METHODS: The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model. RESULTS AND DISCUSSION: In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa. In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model. | 2024 | 39310784 |
| 6284 | 17 | 0.9866 | Acinetobacter baumannii quorum-sensing signalling molecule induces the expression of drug-resistance genes. Quorum-sensing signalling molecules such as N‑acyl homoserine lactones (AHLs) enable certain Gram‑negative bacteria to respond to environmental changes through behaviours, such as biofilm formation and flagellar movement. The present study aimed to identify Acinetobacter baumannii AHLs and assess their influence on antibiotic resistance. A clinical isolate of A. baumannii strain S (AbS) was collected from the wound of a burn patient and high‑performance liquid chromatography and tandem quadrupole or quadrupole time‑of‑flight high‑resolution mass spectrometry was used to identify AbS AHLs. Antibiotic sensitivity was assessed in an AHL‑deficient AbS mutant (AbS‑M), and the expression of drug-resistance genes in the presence of meropenem in AbS, AbS‑M and AbS‑M treated with the AHL N-3-hydroxy-dodecanoyl-homoserine lactone (N‑3‑OH‑C12‑HSL). AbS‑M was more sensitive to meropenem and piperacillin than wild‑type AbS, but resistance was restored by supplementation with N‑3‑OH‑C12‑HSL. In addition, meropenem‑treated AbS‑M expressed lower levels of the drug‑resistance genes oxacillinase 51, AmpC, AdeA and AdeB; treatment with N‑3‑OH‑C12‑HSL also restored the expression of these genes. Overall, the results of the present study indicate that N‑3‑OH‑C12‑HSL may be involved in regulating the expression of drug‑resistance genes in A. baumannii. Therefore, this quorum‑sensing signalling molecule may be an important target for treating multidrug‑resistant A. baumannii infections. | 2017 | 28487993 |
| 9602 | 18 | 0.9866 | Polyhexamethylene biguanide promotes adaptive cross-resistance to gentamicin in Escherichia coli biofilms. Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms -a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice. | 2023 | 38149014 |
| 197 | 19 | 0.9866 | The Interaction of Klebsiella pneumoniae With Lipid Rafts-Associated Cholesterol Increases Macrophage-Mediated Phagocytosis Due to Down Regulation of the Capsule Polysaccharide. Klebsiella pneumoniae successfully colonizes host tissues by recognizing and interacting with cholesterol present on membrane-associated lipid rafts. In this study, we evaluated the role of cholesterol in the expression of capsule polysaccharide genes of K. pneumoniae and its implication in resistance to phagocytosis. Our data revealed that exogenous cholesterol added to K. pneumoniae increases macrophage-mediated phagocytosis. To explain this event, the expression of capsular galF, wzi, and manC genes was determined in the presence of cholesterol. Down-regulation of these capsular genes occurred leading to increased susceptibility to phagocytosis by macrophages. In contrast, depletion of cholesterol from macrophage membranes led to enhanced expression of galF, wzi, and manC genes and to capsule production resulting in resistance to macrophage-mediated phagocytosis. Cholesterol-mediated repression of capsular genes was dependent on the RcsA and H-NS global regulators. Finally, cholesterol also down-regulated the expression of genes responsible for LPS core oligosaccharides production and OMPs. Our results suggest that cholesterol plays an important role for the host by reducing the anti-phagocytic properties of the K. pneumoniae capsule facilitating bacterial engulfment by macrophages during the bacteria-eukaryotic cell interaction mediated by lipid rafts. | 2019 | 31380298 |