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Fulltext Detection of quorum sensing activity in the multidrug-resistant clinical isolate Pseudomonas aeruginosa strain GB11

Cheng HJ, Ee R, Cheong YM, Tan WS, Yin WF, Chan KG

Sensors (Basel), 2014;14(7):12511-22.
PMID: 25019635 DOI: 10.3390/s140712511

A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine lactone (C4-HSL), N-hexanoylhomoserine lactone (C6-HSL), N-octanoyl homoserine lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Fulltext Antibiofilm properties of chemically synthesized silver nanoparticles found against Pseudomonas aeruginosa

Palanisamy NK, Ferina N, Amirulhusni AN, Mohd-Zain Z, Hussaini J, Ping LJ, et al.

J Nanobiotechnology, 2014;12:2.
PMID: 24422704 DOI: 10.1186/1477-3155-12-2

Nanomedicine is now being introduced as a recent trend in the field of medicine. It has been documented that metal nanoparticles have antimicrobial effects for bacteria, fungi and viruses. Recent advances in technology has revived the use of silver nanoparticles in the medical field; treatment, diagnosis, monitoring and control of disease. It has been used since ancient times for treating wide range of illnesses. Bacterial cells adheres to surfaces and develop structures known as biofilms. These structures are natural survival strategy of the bacteria to invade the host. They are more tolerant to commonly used antimicrobial agents, thus being more difficult to be controlled. This leads to increase in severity of infection. In this study, we have investigated the effect of silver nanoparticles in the formation of biofilm in multidrug resistant strains of Pseudomonas aeruginosa. Observation showed that biofilm formation occurred at bacterial concentration of 10(6) cfu/ml for the sensitive strain of P. aeruginosa while in the resistant strain, the biofilm was evident at bacterial concentration of about 10(3) cfu/ml. The biofilm were then tested against various concentrations of silver nanoparticles to determine the inhibitory effect of the silver nanoparticles. In the sensitive strain, 20 μg/ml of silver nanoparticles inhibited the growth optimally at bacterial concentration of 10(4) cfu/ml with an inhibition rate of 67%. Similarly, silver nanoparticles inhibited the formation of biofilm in the resistant strain at an optimal bacterial concentration of 10(5) cfu/ml with an inhibition rate of 56%. Thus, silver nanoparticles could be used as a potential alternative therapy to reduce severity of disease due to P. aeruginosa infections.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Fulltext Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract

Krishnan T, Yin WF, Chan KG

Sensors (Basel), 2012;12(4):4016-30.
PMID: 22666015 DOI: 10.3390/s120404016

Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N-hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-L-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Fulltext Conflict of interest and signal interference lead to the breakdown of honest signaling

Popat R, Pollitt EJ, Harrison F, Naghra H, Hong KW, Chan KG, et al.

Evolution, 2015 Sep;69(9):2371-83.
PMID: 26282874 DOI: 10.1111/evo.12751

Animals use signals to coordinate a wide range of behaviors, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaler. Theory suggests that honest signaling is favored when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signaling to test these predictions with an experimental evolution approach. We show that: (1) reduced relatedness leads to the relative breakdown of signaling, (2) signaling breaks down by the invasion of mutants that show both reduced signaling and reduced response to signal, (3) the genetic route to signaling breakdown is variable, and (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signaling. Our results provide clear support for signaling theory, but we did not find evidence for previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Fulltext Effect of rhamnolipid on the physicochemical properties and interaction of bacteria and fungi

Hamzah N, Kasmuri N, Tao W, Singhal N, Padhye L, Swift S

Braz J Microbiol, 2020 Sep;51(3):1317-1326.
PMID: 32399689 DOI: 10.1007/s42770-020-00295-0

Bacterial adhesion on surfaces is an essential initial step in promoting bacterial mobilization for soil bioremediation process. Modification of the cell surface is required to improve the adhesion of bacteria. The modification of physicochemical properties by rhamnolipid to Pseudomonas putida KT2442, Rhodococcus erythropolis 3586 and Aspergillus brasiliensis ATCC 16404 strains was analysed using contact angle measurements. The surface energy and total free energy of adhesion were calculated to predict the adhesion of both bacteria strains on the A. brasiliensis surface. The study of bacterial adhesion was carried out to evaluate experimental value with the theoretical results. Bacteria and fungi physicochemical properties were modified significantly when treated with rhamnolipid. The adhesion rate of P. putida improved by 16% with the addition of rhamnolipid (below 1 CMC), while the increase of rhamnolipid concentration beyond 1 CMC did not further enhance the bacterial adhesion. The addition of rhamnolipid did not affect the adhesion of R. erythropolis. A good relationship has been obtained in which water contact angle and surface energy of fungal surfaces are the major factors contributing to the bacterial adhesion. The adhesion is mainly driven by acid-base interaction. This finding provides insight to the role of physicochemical properties in controlling the bacterial adhesion on the fungal surface to enhance bacteria transport in soil bioremediation.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Fulltext The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1

Chong YM, How KY, Yin WF, Chan KG

Molecules, 2018 04 21;23(4).
PMID: 29690523 DOI: 10.3390/molecules23040972

The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P.aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C.violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Bioelectricity generation in microbial fuel cell using natural microflora and isolated pure culture bacteria from anaerobic palm oil mill effluent sludge

Nor MH, Mubarak MF, Elmi HSh, Ibrahim N, Wahab MF, Ibrahim Z

Bioresour Technol, 2015 Aug;190:458-65.
PMID: 25799955 DOI: 10.1016/j.biortech.2015.02.103

A double-chambered membrane microbial fuel cell (MFC) was constructed to investigate the potential use of natural microflora anaerobic palm oil mill effluent (POME) sludge and pure culture bacteria isolated from anaerobic POME sludge as inoculum for electricity generation. Sterilized final discharge POME was used as the substrate with no addition of nutrients. MFC operation using natural microflora anaerobic POME sludge showed a maximum power density and current density of 85.11mW/m(2) and 91.12mA/m(2) respectively. Bacterial identification using 16S rRNA analysis of the pure culture isolated from the biofilm on the anode MFC was identified as Pseudomonas aeruginosa strain ZH1. The electricity generated in MFC using P. aeruginosa strain ZH1 showed maximum power density and current density of 451.26mW/m(2) and 654.90mA/m(2) respectively which were five times higher in power density and seven times higher in current density compared to that of MFC using anaerobic POME sludge.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Plant-derived Compounds as Potential Source of Novel Anti-Biofilm Agents Against Pseudomonas aeruginosa

Chung PY

Curr Drug Targets, 2017;18(4):414-420.
PMID: 27758704 DOI: 10.2174/1389450117666161019102025

Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial and life-threatening chronic infections in cystic fibrosis patients. This pathogen is wellknown for its ability to attach to surfaces of indwelling medical devices to form biofilms, which consist of a regular array of extracellular polymers. Tenaciously bound to the surface of devices and inherently resilient to antibiotic treatment, P. aeruginosa poses a serious threat in clinical medicine and contributes to the persistence of chronic infections. Studies on microbial biofilms in the past decade involved mainly the understanding of environment signals, genetic elements and molecular mechanisms in biofilm formation, tolerance and dispersal. The knowledge obtained from the studies of these mechanisms is crucial in the establishment of strategies to eradicate or to prevent biofilm formation. Currently, biofilm infections are usually treated with combinations of antibiotics and surgical removal, in addition to frequent replacement of the infected device. More recently, specific natural sources have been identified as antibiofilm agents against this pathogen. This review will highlight the recent progress made by plant-derived compounds against P. aeruginosa biofilm infections in both in vitro or in vivo models.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Betacyanin-inhibited biofilm formation of co-culture of Staphylococcus aureus and Pseudomonas aeruginosa on different polymer surfaces

Yong YY, Ong MWK, Dykes G, Choo WS

FEMS Microbiol Lett, 2021 01 26;368(1).
PMID: 33338235 DOI: 10.1093/femsle/fnaa214

Staphylococcus aureus and Pseudomonas aeruginosa are bacteria that cause biofilm-associated infections. The aim of this study was to determine the activity of combined betacyanin fractions from Amaranthus dubius (red spinach) and Hylocereus polyrhizus (red pitahaya) against biofilms formed by co-culture of S. aureus and P. aeruginosa on different polymer surfaces. Various formulations containing different concentrations of the betacyanin fractions were investigated for biofilm-inhibiting activity on polystyrene surfaces using crystal violet assay and scanning electron microscopy. A combination of each betacyanin fraction (0.625 mg mL-1) reduced biofilm formation of five S. aureus strains and four P. aeruginosa strains from optical density values of 1.24-3.84 and 1.25-3.52 to 0.81-2.63 and 0.80-1.71, respectively. These combined fractions also significantly inhibited dual-species biofilms by 2.30 and reduced 1.0-1.3 log CFU cm-2 bacterial attachment on polymer surfaces such as polyvinyl chloride, polyethylene, polypropylene and silicone rubber. This study demonstrated an increase in biofilm-inhibiting activity against biofilms formed by two species using combined fractions than that by using single fractions. Betacyanins found in different plants could collectively be used to potentially decrease the risk of biofilm-associated infections caused by these bacteria on hydrophobic polymers.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Antibiofilm activity and mode of action of DMSO alone and its combination with afatinib against Gram-negative pathogens

Yahya MFZR, Alias Z, Karsani SA

Folia Microbiol (Praha), 2018 Jan;63(1):23-30.
PMID: 28540585 DOI: 10.1007/s12223-017-0532-9

Biofilms are complex microbial communities that tend to attach to either biotic or abiotic surface. Enclosed in a self-produced extracellular polymeric substance (EPS) matrix, the biofilms often cause persistent infections. The objective of this study was to investigate the antibiofilm activity of dimethyl sulfoxide (DMSO) and afatinib against Gram-negative pathogens. Test microorganisms used in this study were Escherichia coli ATCC 1299, Pseudomonas aeruginosa ATCC 10145, and Salmonella typhimurium ATCC 14028. Biofilms were developed in 96-well microplate at 37°C for 24 h. Following removal of non-adherent cells, analysis of biofilm viability, biofilm biomass, and extracellular polymeric substances (EPS) matrix were performed using resazurin assay, crystal violet assay, and attenuated total reflectance fourier transform infrared (ATR-FTIR) spectroscopy, respectively. Bradford protein assay was conducted to determine the total amount of EPS proteins. The results demonstrated that both 32% DMSO alone and its combination with 3.2 μg/mL afatinib were effective in killing biofilm cells and reducing biofilm biomass. IR spectral variations of EPS matrix of biofilms in the range between 1700 and 900 cm-1 were also observed. Reduction in EPS proteins verified the chemical modifications of EPS matrix. In conclusion, 32% DMSO alone and its combination with 3.2 μg/mL afatinib showed remarkable antibiofilm activities against Gram-negative pathogens. It was suggested that the biofilm inhibition was mediated by the chemical modification of EPS matrix.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Fulltext Association of some Campylobacter jejuni with Pseudomonas aeruginosa biofilms increases attachment under conditions mimicking those in the environment

Teh AHT, Lee SM, Dykes GA

PLoS One, 2019;14(4):e0215275.
PMID: 30970009 DOI: 10.1371/journal.pone.0215275

Campylobacter jejuni is a microaerophilic bacterial species which is a major food-borne pathogen worldwide. Attachment and biofilm formation have been suggested to contribute to the survival of this fastidious bacteria in the environment. In this study the attachment of three C. jejuni strains (C. jejuni strains 2868 and 2871 isolated from poultry and ATCC 33291) to different abiotic surfaces (stainless steel, glass and polystyrene) alone or with Pseudomonas aeruginosa biofilms on them, in air at 25°C and under static or flow conditions, were investigated using a modified Robbins Device. Bacteria were enumerated and scanning electron microscopy was carried out. The results indicated that both C. jejuni strains isolated from poultry attached better to Pseudomonas aeruginosa biofilms on abiotic surfaces than to the surfaces alone under the different conditions tested. This suggests that biofilms of other bacterial species may passively protect C. jejuni against shear forces and potentially oxygen stress which then contribute to their persistence in environments which are detrimental to them. By contrast the C. jejuni ATCC 33291 strain did not attach differentially to P. aeruginosa biofilms, suggesting that different C. jejuni strains may have alternative strategies for persistence in the environment. This study supports the hypothesis that C. jejuni do not form biofilms per se under conditions they encounter in the environment but simply attach to surfaces or biofilms of other species.

Matched MeSH terms: Pseudomonas aeruginosa/physiology*
Modulation of cell surface hydrophobicity and attachment of bacteria to abiotic surfaces and shrimp by Malaysian herb extracts

Hui YW, Dykes GA

J Food Prot, 2012 Aug;75(8):1507-11.
PMID: 22856578 DOI: 10.4315/0362-028X.JFP-12-062

The use of simple crude water extracts of common herbs to reduce bacterial attachment may be a cost-effective way to control bacterial foodborne pathogens, particularly in developing countries. The ability of water extracts of three common Malaysian herbs (Andrographis paniculata, Eurycoma longifolia, and Garcinia atroviridis) to modulate hydrophobicity and attachment to surfaces of five food-related bacterial strains (Bacillus cereus ATCC 14576, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 10145, Salmonella Enteritidis ATCC 13076, Staphylococcus aureus ATCC 25923) were determined. The bacterial attachment to hydrocarbon assay was used to determine bacterial hydrophobicity. Staining and direct microscopic counts were used to determine attachment of bacteria to glass and stainless steel. Plating on selective media was used to determine attachment of bacteria to shrimp. All extracts were capable of either significantly ( P < 0.05) increasing or decreasing bacterial surface hydrophobicity, depending on the herb extract and bacteria combination. Bacterial attachment to all surfaces was either significantly (P < 0.05) increased or decreased, depending on the herb extract and bacteria combination. Overall, hydrophobicity did not show a significant correlation (P > 0.05) to bacterial attachment. For specific combinations of bacteria, surface material, and plant extract, significant correlations (R > 0.80) between hydrophobicity and attachment were observed. The highest of these was observed for S. aureus attachment to stainless steel and glass after treatment with the E. longifolia extract (R = 0.99, P < 0.01). The crude water herb extracts in this study were shown to have the potential to modulate specific bacterial and surface interactions and may, with further work, be useful for the simple and practical control of foodborne pathogens.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Biofilm inhibiting activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms

Yong YY, Dykes G, Lee SM, Choo WS

J Appl Microbiol, 2019 Jan;126(1):68-78.
PMID: 30153380 DOI: 10.1111/jam.14091

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms.
METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability.
CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene.
SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Determination of the biofilm formation capacity of bacterial pathogens associated with otorhinolaryngologic diseases in the Malaysian population

Khosravi Y, Ling LC, Loke MF, Shailendra S, Prepageran N, Vadivelu J

Eur Arch Otorhinolaryngol, 2014 May;271(5):1227-33.
PMID: 23880921 DOI: 10.1007/s00405-013-2637-3

This study aims to assess the association between microbial composition, biofilm formation and chronic otorhinolaryngologic disorders in Malaysia. A total of 45 patients with chronic rhinosinusitis, chronic tonsillitis and chronic suppurative otitis media and 15 asymptomatic control patients were studied. Swab samples were obtained from these subjects. Samples were studied by conventional microbiological culturing, PCR-based microbial detection and Confocal Laser Scanning Microscopy (CLSM). Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, coagulase-negative staphylococci (CoNS) and other Streptococcus species were detected in subjects of both patient and control groups. Biofilm was observed in approximately half of the smear prepared from swab samples obtained from subjects of the patient group. Most of these were polymicrobial biofilms. S. aureus biofilm was most prevalent among nasal samples while H. influenzae biofilm was more common among ear and throat samples. Results from this study supported the hypothesis that chronic otorhinolaryngologic diseases may be biofilm related. Due to the presence of unculturable bacteria in biofilms present in specimens from ear, nose and throat, the use of molecular methods in combination with conventional microbiological culturing has demonstrated an improvement in the detection of bacteria from such specimens in this study.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Fulltext Gut bacteria of Cuora amboinensis (turtle) produce broad-spectrum antibacterial molecules

Akbar N, Khan NA, Sagathevan K, Iqbal M, Tawab A, Siddiqui R

Sci Rep, 2019 11 18;9(1):17012.
PMID: 31740685 DOI: 10.1038/s41598-019-52738-w

Antimicrobial resistance is a major threat to human health, hence there is an urgent need to discover antibacterial molecule(s). Previously, we hypothesized that microbial gut flora of animals are a potential source of antibacterial molecules. Among various animals, Cuora amboinensis (turtle) represents an important reptile species living in diverse ecological environments and feed on organic waste and terrestrial organisms and have been used in folk medicine. The purpose of this study was to mine turtle's gut bacteria for potential antibacterial molecule(s). Several bacteria were isolated from the turtle gut and their conditioned media were prepared. Conditioned media showed potent antibacterial activity against several Gram-positive (Bacillus cereus, Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus) and Gram-negative (neuropathogenic Escherichia coli K1, Serratia marcescens, Pseudomonas aeruginosa, Salmonella enterica and Klebsiella pneumoniae) pathogenic bacteria. Conditioned media-mediated bactericidal activity was heat-resistant when treated at 95°C for 10 min. By measuring Lactate dehydrogenase release, the results showed that conditioned media had no effect on human cell viability. Tandem Mass Spectrometric analysis revealed the presence of various secondary metabolites, i.e., a series of known as well as novel N-acyl-homoserine lactones, several homologues of 4-hydroxy-2-alkylquinolines, and rhamnolipids, which are the signature metabolites of Pseudomonas species. These findings are significant and provide the basis for rational development of therapeutic interventions against bacterial infections.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity

Lee WT, Tan BK, Eng SA, Yuen GC, Chan KL, Sim YK, et al.

Food Funct, 2019 Sep 01;10(9):5759-5767.
PMID: 31453615 DOI: 10.1039/c9fo01357a

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.

Matched MeSH terms: Pseudomonas aeruginosa/physiology
Sweetening Inhaled Antibiotic Treatment for Eradication of Chronic Respiratory Biofilm Infection

Loo CY, Lee WH, Lauretani G, Scalia S, Cipolla D, Traini D, et al.

Pharm Res, 2018 Feb 07;35(3):50.
PMID: 29417313 DOI: 10.1007/s11095-018-2350-4

PURPOSE: The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm.
METHOD: Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy.
RESULTS: Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone.
CONCLUSIONS: The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.

Matched MeSH terms: Pseudomonas aeruginosa/physiology

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