# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 6359 | 0 | 0.9863 | Drug resistance of oral bacteria to new antibacterial dental monomer dimethylaminohexadecyl methacrylate. Only two reports exist on drug-resistance of quaternary ammonium monomers against oral bacteria; both studies tested planktonic bacteria for 10 passages, and neither study tested biofilms or resins. The objectives of this study were to investigate the drug-resistance of Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii against dimethylaminohexadecyl methacrylate (DMAHDM), and to evaluate biofilms on resins with repeated exposures for 20 passages for the first time. DMAHDM, dimethylaminododecyl methacrylate (DMADDM) and chlorhexidine (CHX) were tested with planktonic bacteria. Biofilms were grown on a resin containing 3% DMAHDM. Minimum-inhibitory concentrations were measured. To detect drug-resistance, the survived bacteria from the previous passage were used as inoculum for the next passage for repeated exposures. S. gordonii developed drug-resistance against DMADDM and CHX, but not against DMAHDM. Biofilm colony-forming units (CFU) on DMAHDM-resin was reduced by 3-4 log; there was no difference from passages 1 to 20 (p > 0.1). No drug-resistance to DMAHDM was detected for all three bacterial species. In conclusion, this study showed that DMAHDM induced no drug-resistance, and DMAHDM-resin reduced biofilm CFU by 3-4 log, with no significant change from 1 to 20 passages. DMAHDM with potent antibacterial activities and no drug-resistance is promising for dental applications. | 2018 | 29615732 |
| 8737 | 1 | 0.9850 | Role of Biosynthetic Gene Cluster BGC3 in the Cariogenic Virulence of Streptococcus mutans. OBJECTIVE: To investigate the role of the biosynthetic gene cluster BGC3 of Streptococcus mutans (S. mutans) in the process of dental caries. METHODS: BGC3 and ∆BGC3 S. mutans strains were constructed and their growth curves were evaluated. Acid production capacity was assessed by evaluating pH reduction levels over identical culture periods. The survival of bacteria in phosphate citrate buffer solution (pH 3.0) was quantified. The expression levels of virulence genes (atpF, gtfC, gtfD, spaP, vicR and ftf) were analysed using the qPCR. Co-culture experiments were conducted to evaluate bacterial adaptability. Bacterial viability was determined by microscopical examination of live/dead staining. RESULTS: Deletion of BGC3 did not significantly impact S. mutans growth or acid production in biofilms. The ∆BGC3 strain exhibited enhanced acid resistance and higher expression levels of virulence genes compared to the wild type. In addition, ∆BGC3 exhibited superior bacterial viability in the co-culture system. CONCLUSION: BGC3 affected the acid resistance and expression of caries-related genes in S. mutans. The BGC3 knockout strain exhibited a more robust survival capability than the wild-type strain. | 2025 | 40162656 |
| 8863 | 2 | 0.9846 | Resistance and tolerance to tropodithietic acid, an antimicrobial in aquaculture, is hard to select. The antibacterial compound tropodithietic acid (TDA) is produced by bacteria of the marine Roseobacter clade and is thought to explain the fish probiotic properties of some roseobacters. The aim of the present study was to determine the antibacterial spectrum of TDA and the likelihood of development of TDA resistance. A bacterial extract containing 95% TDA was effective against a range of human-pathogenic bacteria, including both Gram-negative and Gram-positive bacteria. TDA was bactericidal against Salmonella enterica serovar Typhimurium SL1344 and Staphylococcus aureus NCTC 12493 and killed both growing and nongrowing cells. Several experimental approaches were used to select mutants resistant to TDA or subpopulations of strains with enhanced tolerance to TDA. No approach (single exposures to TDA extract administered via different methods, screening of a transposon library for resistant mutants, or prolonged exposure to incremental concentrations of TDA) resulted in resistant or tolerant strains. After more than 300 generations exposed to sub-MIC and MIC concentrations of a TDA-containing extract, strains tolerant to 2× the MIC of TDA for wild-type strains were selected, but the tolerance disappeared after one passage in medium without TDA extract. S. Typhimurium mutants with nonfunctional efflux pump and porin genes had the same TDA susceptibility as wild-type strains, suggesting that efflux pumps and porins are not involved in innate tolerance to TDA. TDA is a promising broad-spectrum antimicrobial in part due to the fact that enhanced tolerance is difficult to gain and that the TDA-tolerant phenotype appears to confer only low-level resistance and is very unstable. | 2011 | 21263047 |
| 9064 | 3 | 0.9844 | Bacillus subtilis var. natto increases the resistance of Caenorhabditis elegans to gram-positive bacteria. AIMS: This study aimed to investigate the effect of Bacillus subtilis var. natto on the susceptibility of the model host, Caenorhabditis elegans, to bacterial infection. METHODS AND RESULTS: Caenorhabditis elegans worms were fed with a standard food consisting of Escherichia coli OP50 strain (control) or B. subtilis (natto) during their larval stage. The worms were then infected with pathogenic bacteria. We analyzed their survival time and RNA sequencing-based transcriptome. Upon infection with Staphylococcus aureus and Enterococcus faecalis, the survival time of B. subtilis (natto)-fed worms was longer than that of the control. Transcriptome analyses showed upregulation of genes associated with innate immunity and defense response to gram-positive bacteria in B. subtilis (natto)-fed worms. CONCLUSIONS: Bacillus subtilis (natto) conferred an increased resistance of C. elegans to gram-positive bacteria. Our findings provided insights into the molecular mechanisms underlying B. subtilis (natto)-regulated host immunity and emphasized its probiotic properties for preventing and alleviating infections caused by gram-positive bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first study to show that B. subtilis (natto) confers specific resistance against gram-positive bacteria. | 2021 | 34157196 |
| 8860 | 4 | 0.9844 | Antibiotic in myrrh from Commiphora molmol preferentially kills nongrowing bacteria. AIM: To demonstrate that myrrh oil preferentially kills nongrowing bacteria and causes no resistance development. METHOD: Growth inhibition was determined on regular plates or plates without nutrients, which were later overlaid with soft agar containing nutrients to continue growth. Killing experiments were done in broth and in buffer without nutrients. RESULTS: Bacterial cells were inhibited preferentially in the absence of nutrients or when growth was halted by a bacteriostatic antibiotic. After five passages in myrrh oil, surviving colonies showed no resistance to the antibiotic. CONCLUSION: Myrrh oil has the potential to be a commercially viable antibiotic that kills persister cells and causes no resistance development. This is a rare example of an antibiotic that can preferentially kill nongrowing bacteria. | 2020 | 32257371 |
| 6373 | 5 | 0.9842 | Antibiotic resistance and multidrug-resistant efflux pumps expression in lactic acid bacteria isolated from pozol, a nonalcoholic Mayan maize fermented beverage. Pozol is a handcrafted nonalcoholic Mayan beverage produced by the spontaneous fermentation of maize dough by lactic acid bacteria. Lactic acid bacteria (LAB) are carriers of chromosomal encoded multidrug-resistant efflux pumps genes that can be transferred to pathogens and/or confer resistance to compounds released during the fermentation process causing food spoiling. The aim of this study was to evaluate the antibiotic sensibility and the transcriptional expression of ABC-type efflux pumps in LAB isolated from pozol that contributes to multidrug resistance. Analysis of LAB and Staphylococcus (S.) aureus ATCC 29213 and ATCC 6538 control strains to antibiotic susceptibility, minimal inhibitory concentration (MIC), and minimal bactericidal concentration (MBC) to ethidium bromide were based in "standard methods" whereas the ethidium bromide efflux assay was done by fluorometric assay. Transcriptional expression of efflux pumps was analyzed by RT-PCR. LAB showed antibiotic multiresistance profiles, moreover, Lactococcus (L.) lactis and Lactobacillus (L.) plantarum displayed higher ethidium bromide efflux phenotype than S. aureus control strains. Ethidium bromide resistance and ethidium bromide efflux phenotypes were unrelated with the overexpression of lmrD in L. lactics, or the underexpression of lmrA in L. plantarum and norA in S. aureus. These findings suggest that, moreover, the analyzed efflux pumps genes, other unknown redundant mechanisms may underlie the antibiotic resistance and the ethidium bromide efflux phenotype in L. lactis and L. plantarum. Phenotypic and molecular drug multiresistance assessment in LAB may improve a better selection of the fermentation starter cultures used in pozol, and to control the antibiotic resistance widespread and food spoiling for health safety. | 2016 | 27247772 |
| 6368 | 6 | 0.9842 | Antibacterial effects of curcumin encapsulated in nanoparticles on clinical isolates of Pseudomonas aeruginosa through downregulation of efflux pumps. Curcumin as a flavonoid from the rhizome of Curcuma longa has antibacterial, antiviral and antifungal activity. Multidrug resistance in pathogenic bacteria is continuously increasing in hospitals. The aim of this study was to investigate the effect of curcumin encapsulated in micellar/polymersome nanoparticles as an efflux pump inhibitor (EPI) on the expression of mexX and oprM genes in curcumin-treated and -untreated isolates of Pseudomonas aeruginosa. Clinical isolates of Pseudomonas aeruginosa were treated with ciprofloxacin (sub-MICs) alone and/or in combination with curcumin-encapsulated in micellar/polymersome nanoparticles. The expression of mexX and oprM genes was quantitatively evaluated by qRT-PCR in curcumin-treated and -untreated bacteria after 24 h. Curcumin-encapsulated in nanoparticles (400 µg/mL) induced cell death up to 50% in ciprofloxacin-treated (1/2MIC) resistant isolates during 24 h, while the bacteria treated with ciprofloxacin (without curcumin) were not inhibited. Also, curcumin in different concentrations increased effect of ciprofloxacin (sub-MICs). Downregulation of mexX and oprM genes was observed in cells treated with curcumin and ciprofloxacin compared to cells treated with ciprofloxacin alone. It seems that curcumin can be used as complementary drug in ciprofloxacin-resistant isolates through downregulating genes involved in efflux pumps and trapping ciprofloxacin on bacterial cells and increasing the effects of drug. | 2019 | 30778922 |
| 4763 | 7 | 0.9841 | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in Staphylococcus aureus with Divergent Resistance Phenotypes. Healthcare-associated methicillin-resistant Staphylococcus aureus infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria's molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of OrfX, SpdC and WalKR was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria's molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms. | 2023 | 36978386 |
| 8941 | 8 | 0.9841 | Salicylate reduces the antimicrobial activity of ciprofloxacin against extracellular Salmonella enterica serovar Typhimurium, but not against Salmonella in macrophages. OBJECTIVES: Salicylate, a potent inducer of the MarA activator in Salmonella enterica, is the principal metabolite of aspirin, which is often consumed for medicinal and cosmetic uses. Our research was aimed at testing if salicylate activates the mar regulon in macrophage-associated Salmonella (intracellular bacteria), and investigating its effects on bacterial susceptibility to ciprofloxacin extracellularly and intracellularly. METHODS: J774 macrophages were infected with S. enterica serovar Typhimurium (wild-type and marA null mutant), treated with ciprofloxacin with and without pre-exposure to salicylate, and the surviving bacteria were counted. Similar experiments were conducted with bacteria in broth (extracellular bacteria). Phe-Arg-beta-naphthylamide (PAbetaN) was added to investigate the role of efflux pumps in resistance. The transcriptional regulation of marRAB, acrAB and micF in extracellular and intracellular Salmonella Typhimurium with and without salicylate and ciprofloxacin was investigated using green fluorescent protein as a marker protein and quantitative real time PCR. RESULTS: Pre-exposure of Salmonella to salicylate increased the resistance of extracellular but not intracellular bacteria to ciprofloxacin, although salicylate stimulated the expression of mar genes in intracellular and extracellular bacteria. Using marA mutants and the inhibitor PAbetaN, we showed that the improved resistance in extracellular bacteria is derived from the induction of acrAB by salicylate, which is mediated by MarA. CONCLUSIONS: In intracellular bacteria, the expression of acrAB is already higher when compared with extracellular cells; therefore, salicylate does not result in significant acrAB induction intracellularly and subsequent resistance enhancement. Results show that conclusions raised from extracellular studies cannot be applied to intracellular bacteria, although the systems have similar functions. | 2010 | 20237076 |
| 9065 | 9 | 0.9841 | Gut Bacteria Promote Phosphine Susceptibility of Tribolium castaneum by Aggravating Oxidative Stress and Fitness Costs. Knowledge about resistance mechanisms can provide ideas for pesticide resistance management. Although several studies have unveiled the positive or negative impacts of gut microbes on host pesticide resistance, minimal research is available regarding the association between gut microbes and host phosphine resistance. To explore the influence of gut bacteria on host phosphine susceptibility and its molecular basis, mortality, fitness, redox responses, and immune responses of adult Tribolium castaneum were determined when it was challenged by phosphine exposure and/or gut bacteria inoculation. Five cultivable gut bacteria were excised from a population of phosphine-resistant T. castaneum. Among them, only Enterococcus sp. inoculation significantly promoted host susceptibility to phosphine, while inoculation of any other gut bacteria had no significant effect on host phosphine susceptibility. Furthermore, when T. castaneum was exposed to phosphine, Enterococcus sp. inoculation decreased the female fecundity, promoted host oxidative stress, and suppressed the expression and activity of host superoxide dismutase, catalase, and peroxidase. In the absence of phosphine, Enterococcus sp. inoculation also elicited overactive immune responses in T. castaneum, including the immune deficiency and Toll signaling pathways and the dual oxidase-reactive oxygen species system. These results indicate that Enterococcus sp. likely promotes host phosphine susceptibility by aggravating oxidative stress and fitness costs. | 2023 | 37887827 |
| 6229 | 10 | 0.9840 | Response of Bacillus cereus ATCC 14579 to challenges with sublethal concentrations of enterocin AS-48. BACKGROUND: Enterocin AS-48 is produced by Enterococcus faecalis S48 to compete with other bacteria in their environment. Due to its activity against various Gram positive and some Gram negative bacteria it has clear potential for use as a food preservative. Here, we studied the effect of enterocin AS-48 challenges on vegetative cells of Bacillus cereus ATCC 14579 by use of transcriptome analysis. RESULTS: Of the 5200 genes analysed, expression of 24 genes was found to change significantly after a 30 min treatment with a subinhibitory bacteriocin concentration of 0.5 microg/ml. Most of up-regulated genes encode membrane-associated or secreted proteins with putative transmembrane segments or signal sequences, respectively. One operon involved in arginine metabolism was significantly downregulated. The BC4206-BC4207 operon was found to be the most upregulated target in our experiments. BC4206 codes for a PadR type transcriptional regulator, while BC4207 codes for a hypothetical membrane protein. The operon structure and genes are conserved in B. cereus and B. thuringiensis species, but are not present in B. anthracis and B. subtilis. Using real-time qPCR, we show that these genes are upregulated when we treated the cells with AS-48, but not upon nisin treatment. Upon overexpression of BC4207 in B. cereus, we observed an increased resistance against AS-48. Expression of BC4207 in B. subtilis 168, which lacks this operon also showed increased resistance against AS-48. CONCLUSION: BC4207 membrane protein is involved in the resistance mechanism of B. cereus cells against AS-48. | 2009 | 19863785 |
| 4764 | 11 | 0.9840 | Effect of lipopeptide extracted from Bacillus licheniformis on the expression of bap and luxI genes in multi-drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Recently, opportunistic pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa have caused concern due to their ability to cause antibiotic resistance in weakened immune systems. As a result, researchers are always seeking efficient antimicrobial agents to tackle this issue. The hypothesis of the recent study was that probiotic products derived from bacteria would be effective in reducing drug resistance in other bacteria. This research aimed to investigate the antimicrobial properties of probiotic products from various bacterial strains, including Lactobacillus rhamnosus, Pediococcus acidilactisi, Bacillus coagulans, Bacillus subtilis, and Bacillus licheniformis. These were tested against multi-drug-resistant (MDR) standard strains A. baumannii and P. aeruginosa. B. licheniformis was found to be the most effective probiotic strain, possessing the LanA and LanM lantibiotic genes. The lipopeptide nature of the probiotic product was confirmed through high-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR) techniques. The anti-biofilm and antimicrobial properties of this probiotic were measured using an SEM electron microscope and minimum inhibitory concentration (MIC) test. Real-time PCR (qPCR) was used to compare the expression of bap and luxI genes, which are considered virulence factors of drug-resistant bacteria, before and after treatment with antimicrobial agents. The MIC results showed that the probiotic product prevented the growth of bacteria at lower concentrations compared to antibiotics. In addition, the ΔΔCqs indicated that gene expression was significantly down-regulated following treatment with the obtained probiotic product. It was found that B. licheniformis probiotic products could reduce drug resistance in other bacteria, making it a potential solution to antibiotic resistance. | 2023 | 37907777 |
| 4767 | 12 | 0.9840 | The impact of probiotic cell-free metabolites in MDR Pseudomonas aeruginosa: antibacterial properties and effect on antibiotic resistance genes expression. There is a significant demand for novel antibacterial agents against multidrug-resistant (MDR) gram-negative bacteria. Recently, probiotics have been noted for their antibacterial properties against various pathogens. This study aimed to investigate the effects of probiotic cell-free supernatants on MDR Pseudomonas aeruginosa. Clinical isolates demonstrating the highest degree of antibiotic resistance were chosen, and the antibacterial effect of probiotic metabolites was evaluated using an agar-well diffusion assay. In addition, the effect of probiotics on the expression of resistance genes was evaluated using real-time PCR. The CFS was assessed using GC-MS to determine the antibacterial compounds. The supernatants inhibited the growth of the isolates (P < 0.0001); however, there was no noticeable difference in the effectiveness of the probiotics. In addition, the supernatants decreased the expression levels of mexD, mexB, mexF, and ampC, and an increase in oprD was observed in some groups. After the assessment of Lactobacillus acidophilus by GC-MS, antibacterial compounds, such as acetamide, nonadecane, 9-methyl, and tetradecane, were determined. Our findings showed that probiotic metabolites can effectively inhibit the growth of MDR P. aeruginosa. Gene expression analysis also revealed that the mechanism of antibacterial action was most likely related to the regulation of efflux pumps. | 2023 | 37742315 |
| 5168 | 13 | 0.9839 | Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and the Type IX Secretion System. Increasing problems with antibiotic resistance have directed interest toward phage therapy in the aquaculture industry. However, phage resistance evolving in target bacteria is considered a challenge. To investigate how phage resistance influences the fish pathogen Flavobacterium columnare, two wild-type bacterial isolates, FCO-F2 and FCO-F9, were exposed to phages (FCO-F2 to FCOV-F2, FCOV-F5, and FCOV-F25, and FCO-F9 to FCL-2, FCOV-F13, and FCOV-F45), and resulting phenotypic and genetic changes in bacteria were analyzed. Bacterial viability first decreased in the exposure cultures but started to increase after 1 to 2 days, along with a change in colony morphology from original rhizoid to rough, leading to 98% prevalence of the rough morphotype. Twenty-four isolates (including four isolates from no-phage treatments) were further characterized for phage resistance, antibiotic susceptibility, motility, adhesion, and biofilm formation, protease activity, whole-genome sequencing, and virulence in rainbow trout fry. The rough isolates arising in phage exposure were phage resistant with low virulence, whereas rhizoid isolates maintained phage susceptibility and high virulence. Gliding motility and protease activity were also related to the phage susceptibility. Observed mutations in phage-resistant isolates were mostly located in genes encoding the type IX secretion system, a component of the Bacteroidetes gliding motility machinery. However, not all phage-resistant isolates had mutations, indicating that phage resistance in F. columnare is a multifactorial process, including both genetic mutations and changes in gene expression. Phage resistance may not, however, be a challenge for development of phage therapy against F. columnare infections since phage resistance is associated with decreases in bacterial virulence. IMPORTANCE Phage resistance of infectious bacteria is a common phenomenon posing challenges for the development of phage therapy. Along with a growing world population and the need for increased food production, constantly intensifying animal farming has to face increasing problems of infectious diseases. Columnaris disease, caused by Flavobacterium columnare, is a worldwide threat for salmonid fry and juvenile farming. Without antibiotic treatments, infections can lead to 100% mortality in a fish stock. Phage therapy of columnaris disease would reduce the development of antibiotic-resistant bacteria and antibiotic loads by the aquaculture industry, but phage-resistant bacterial isolates may become a risk. However, phenotypic and genetic characterization of phage-resistant F. columnare isolates in this study revealed that they are less virulent than phage-susceptible isolates and thus not a challenge for phage therapy against columnaris disease. This is valuable information for the fish farming industry globally when considering phage-based prevention and curing methods for F. columnare infections. | 2021 | 34106011 |
| 9088 | 14 | 0.9839 | Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy. Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria. | 2023 | 37150990 |
| 9027 | 15 | 0.9839 | Scorpion Venom Antimicrobial Peptides Induce Siderophore Biosynthesis and Oxidative Stress Responses in Escherichia coli. The increasing development of microbial resistance to classical antimicrobial agents has led to the search for novel antimicrobials. Antimicrobial peptides (AMPs) derived from scorpion and snake venoms offer an attractive source for the development of novel therapeutics. Smp24 (24 amino acids [aa]) and Smp43 (43 aa) are broad-spectrum AMPs that have been identified from the venom gland of the Egyptian scorpion Scorpio mauruspalmatus and subsequently characterized. Using a DNA microarray approach, we examined the transcriptomic responses of Escherichia coli to subinhibitory concentrations of Smp24 and Smp43 peptides following 5 h of incubation. Seventy-two genes were downregulated by Smp24, and 79 genes were downregulated by Smp43. Of these genes, 14 genes were downregulated in common and were associated with bacterial respiration. Fifty-two genes were specifically upregulated by Smp24. These genes were predominantly related to cation transport, particularly iron transport. Three diverse genes were independently upregulated by Smp43. Strains with knockouts of differentially regulated genes were screened to assess the effect on susceptibility to Smp peptides. Ten mutants in the knockout library had increased levels of resistance to Smp24. These genes were predominantly associated with cation transport and binding. Two mutants increased resistance to Smp43. There was no cross-resistance in mutants resistant to Smp24 or Smp43. Five mutants showed increased susceptibility to Smp24, and seven mutants showed increased susceptibility to Smp43. Of these mutants, formate dehydrogenase knockout (fdnG) resulted in increased susceptibility to both peptides. While the electrostatic association between pore-forming AMPs and bacterial membranes followed by integration of the peptide into the membrane is the initial starting point, it is clear that there are numerous subsequent additional intracellular mechanisms that contribute to their overall antimicrobial effect.IMPORTANCE The development of life-threatening resistance of pathogenic bacteria to the antibiotics typically in use in hospitals and the community today has led to an urgent need to discover novel antimicrobial agents with different mechanisms of action. As an ancient host defense mechanism of the innate immune system, antimicrobial peptides (AMPs) are attractive candidates to fill that role. Scorpion venoms have proven to be a rich source of AMPs. Smp24 and Smp43 are new AMPs that have been identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, and these peptides can kill a wide range of bacterial pathogens. By better understanding how these AMPs affect bacterial cells, we can modify their structure to make better drugs in the future. | 2021 | 33980680 |
| 6372 | 16 | 0.9839 | Sensitizing multi drug resistant Staphylococcus aureus isolated from surgical site infections to antimicrobials by efflux pump inhibitors. BACKGROUND: Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resistant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. METHODS: Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilution method. RESULTS: Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. CONCLUSION: Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials. | 2020 | 34394224 |
| 8963 | 17 | 0.9839 | Photodynamic therapy on mRNA levels in bacteria. Antimicrobial photodynamic therapy (aPDT) has shown efficacy in inactivating different bacterial species by photosensitizer-induced free radical production. Despite aPDT is considered unable to cause resistant strains, enzymatic pathways for detoxification of reactive oxygen species and transmembrane photosensitizer efflux systems could cause resistance to aPDT. Resistance mechanisms can be evaluated by measurement of mRNA from by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Thus, the aim of this study was to access the mRNA level data obtained by RT-qPCR in bacterial cells submitted to photodynamic therapy. Studies performed on mRNA levels in bacteria after PDT were assessed on MEDLINE/Pubmed. The mRNA levels from genes related to various functions have been successfully evaluated in both Gram-positive and -negative bacteria after aPDT by RT-qPCR. Such an approach has improved the understanding of aPDT-induced effects, and reinforced the effectiveness of aPDT on bacteria, which can cause infections in different human tissues. | 2024 | 39214913 |
| 9026 | 18 | 0.9839 | Citral and its derivatives inhibit quorum sensing and biofilm formation in Chromobacterium violaceum. With an upsurge in multidrug resistant bacteria backed by biofilm defence armours, there is a desperate need of new antibiotics with a non-traditional mechanism of action. Targeting bacteria by misguiding them or halting their communication is a new approach that could offer a new way to combat the multidrug resistance problem. Quorum sensing is considered to be the achilles heel of bacteria that has a lot to offer. Since, both quorum sensing and biofilm formation have been related to drug resistance and pathogenicity, in this study we synthesised new derivatives of citral with antiquorum sensing and biofilm disrupting properties. We previously reported antimicrobial and antiquorum sensing activity of citral and herein we report the synthesis and evaluation of citral and its derivatives (CD1-CD3) for antibacterial, antibiofilm and antiquorum sensing potential against Chromobacterium violaceum using standard methods. Preliminary results revealed that CD1 is the most active of all the derivatives. Qualitative and quantitative evaluation of antiquorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for CD1 followed by CD2, CD3 and citral. These compounds also inhibit biofilm formation at subinhibitory concentrations without causing any bacterial growth inhibition. These results were replicated by RT-qPCR with down regulation of the quorum sensing genes when C. violaceum was treated with these test compounds. Overall, the results are quite encouraging, revealing that biofilm and quorum sensing are interrelated processes and also indicating the potential of these derivatives to impede bacterial communication and biofilm formation. | 2021 | 33392626 |
| 2476 | 19 | 0.9838 | A Novel and Quantitative Detection Assay (effluxR) for Identifying Efflux-Associated Resistance Genes Using Multiplex Digital PCR in Clinical Isolates of Pseudomonas aeruginosa. The rise of multidrug resistance of Pseudomonas aeruginosa highlights an increased need for selective and precise antimicrobial treatment. Drug efflux pumps are one of the major mechanisms of antimicrobial resistance found in many bacteria, including P. aeruginosa. Detection of efflux genes using a polymerase chain reaction (PCR)-based system would enable resistance detection and aid clinical decision making. Therefore, we aimed to develop and optimize a novel method herein referred to as "effluxR detection assay" using multiplex digital PCR (mdPCR) for detection of mex efflux pump genes in P. aeruginosa strains. The annealing/extension temperatures and gDNA concentrations were optimized to amplify mexB, mexD, and mexY using the multiplex quantitative PCR (mqPCR) system. We established the optimal mqPCR conditions for the assay (Ta of 59 °C with gDNA concentrations at or above 0.5 ng/µL). Using these conditions, we were able to successfully detect the presence of these genes in a quantity-dependent manner. The limit of detection for mex genes using the effluxR detection assay with mdPCR was 0.001 ng/µL (7.04-34.81 copies/µL). Moreover, using blind sample testing, we show that effluxR detection assay had 100% sensitivity and specificity for detecting mex genes in P. aeruginosa. In conclusion, the effluxR detection assay, using mdPCR, is able to identify the presence of multiple mex genes in P. aeruginosa that may aid clinical laboratory decisions and further epidemiological studies. | 2023 | 37888028 |