scholarly journals Cinnamaldehyde Induces Expression of Efflux Pumps and Multidrug Resistance in Pseudomonas aeruginosa

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Alexandre Tetard ◽  
Andy Zedet ◽  
Corine Girard ◽  
Patrick Plésiat ◽  
Catherine Llanes
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Content Adaptation ◽  
Toxic Metabolite ◽  
Regulatory Pathway ◽  
Content Type ◽  
Antagonistic Effects ◽  
Cinnamon Bark ◽  
Therapeutic Consequences

ABSTRACT Essential oils or their components are increasingly used to fight bacterial infections. Cinnamaldehyde (CNA), the main constituent of cinnamon bark oil, has demonstrated interesting properties in vitro against various pathogens, including Pseudomonas aeruginosa. In the present study, we investigated the mechanisms and possible therapeutic consequences of P. aeruginosa adaptation to CNA. Exposure of P. aeruginosa PA14 to subinhibitory concentrations of CNA caused a strong albeit transient increase in the expression of operons that encode the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY/OprM. This multipump activation enhanced from 2- to 8-fold the resistance (MIC) of PA14 to various antipseudomonal antibiotics, including meropenem, ceftazidime, tobramycin, and ciprofloxacin. CNA-induced production of pump MexAB-OprM was found to play a major role in the adaption of P. aeruginosa to the electrophilic biocide, through the NalC regulatory pathway. CNA was progressively transformed by bacteria into the less toxic metabolite cinnamic alcohol (CN-OH), via yet undetermined detoxifying mechanisms. In conclusion, the use of cinnamon bark oil or cinnamaldehyde as adjunctive therapy to treat P. aeruginosa infections may potentially have antagonistic effects if combined with antibiotics because of Mex pump activation.

scholarly journals Evolution of Pseudomonas aeruginosa Virulence as a Result of Phage Predation

2013 ◽  
Vol 79 (19) ◽  
pp. 6110-6116 ◽  
Author(s):  
Zeinab Hosseinidoust ◽  
Theo G. M. van de Ven ◽  
Nathalie Tufenkji
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
Membrane Damage ◽  
Human Keratinocytes ◽  
Host Population ◽  
Resistant Bacteria ◽  
Content Type ◽  
Metabolic Action

ABSTRACTThe rapid increase in the emergence of antibiotic-resistant bacteria has attracted attention to bacteriophages for treating and preventing bacterial infections. Bacteriophages can drive the diversification ofPseudomonas aeruginosa, giving rise to phage-resistant variants with different phenotypes from their ancestral hosts. In this study, we sought to investigate the effect of phage resistance on cytotoxicity of host populations toward cultured mammalian cells. The library of phage-resistantP. aeruginosaPAO1 variants used was developed previously via experimental evolution of an isogenic host population using phages PP7 and E79. Our results presented herein indicate that the phage-resistant variants developed in a heterogeneous phage environment exhibit a greater ability to impede metabolic action of cultured human keratinocytes and have a greater tendency to cause membrane damage even though they cannot invade the cells in large numbers. They also show a heightened resistance to phagocytosis by model murine macrophages. Furthermore, all isolates produced higher levels of at least one of the secreted virulence factors, namely, total proteases, elastase, phospholipase C, and hemolysins. Reverse transcription-quantitative PCR (RT-qPCR) revealed upregulation in the transcription of a number of genes associated with virulence ofP. aeruginosafor the phage-resistant variants. The results of this study indicate a significant change in thein vitrovirulence ofP. aeruginosafollowing phage predation and highlight the need for caution in the selection and design of phages and phage cocktails for therapeutic use.

scholarly journals Synergy of Silver Nanoparticles and Aztreonam against Pseudomonas aeruginosa PAO1 Biofilms

2014 ◽  
Vol 58 (10) ◽  
pp. 5818-5830 ◽  
Author(s):  
Marc B. Habash ◽  
Amber J. Park ◽  
Emily C. Vis ◽  
Robert J. Harris ◽  
Cezar M. Khursigara
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Antimicrobial Properties ◽  
Planktonic Cell ◽  
Chronic Infections ◽  
Content Type

ABSTRACTPathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to the inherent architecture of the biofilm community. The protection provided by the biofilm limits antimicrobial dispersion and penetration and reduces the efficacy of antibiotics that normally inhibit planktonic cell growth. Thus, alternative antimicrobial strategies are required to combat persistent infections. The antimicrobial properties of silver have been known for decades, but silver and silver-containing compounds have recently seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the efficacy of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the monobactam antibiotic aztreonam, to inhibitPseudomonas aeruginosaPAO1 biofilms. Among the different sizes of AgNPs examined, 10-nm nanoparticles were most effective in inhibiting the recovery ofP. aeruginosabiofilm cultures and showed synergy of inhibition when combined with sub-MIC levels of aztreonam. Visualization of biofilms treated with combinations of 10-nm AgNPs and aztreonam indicated that the synergistic bactericidal effects are likely caused by better penetration of the small AgNPs into the biofilm matrix, which enhances the deleterious effects of aztreonam against the cell envelope ofP. aeruginosawithin the biofilms. These data suggest that small AgNPs synergistically enhance the antimicrobial effects of aztreonam againstP. aeruginosain vitro, and they reveal a potential role for combinations of small AgNPs and antibiotics in treating patients with chronic infections.

scholarly journals Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Michael A. Pfaller ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Antimicrobial Surveillance ◽  
Broth Microdilution Method

ABSTRACT The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillin-tazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.

scholarly journals A Dimer, but Not Monomer, of Tobramycin Potentiates Ceftolozane against Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa and Delays Resistance Development

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Temilolu Idowu ◽  
George G. Zhanel ◽  
Frank Schweizer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
In The Wild ◽  
Tract Infections ◽  
Hospital Acquired

ABSTRACT Ceftolozane-tazobactam is a potent β-lactam/β-lactamase inhibitor combination approved for the treatment of complicated intraabdominal and complicated urinary tract infections and, more recently, the treatment of hospital-acquired and ventilator-associated bacterial pneumonia. Although the activities of ceftolozane are not enhanced by tazobactam against Pseudomonas aeruginosa, it remains the most potent antipseudomonal agent approved to date. Emerging data worldwide has included reports of microbiological failure in patients with serious bacterial infections caused by multidrug-resistant (MDR) P. aeruginosa as a result of ceftolozane resistance developed within therapy. The objective of this study is to compare the efficacy of a tobramycin homodimer plus ceftolozane versus ceftolozane-tazobactam alone against MDR and extensively drug-resistant (XDR) P. aeruginosa. Tobramycin homodimer, a synthetic dimer of two monomeric units of tobramycin, was developed to abrogate the ribosomal properties of tobramycin with a view to mitigating aminoglycoside-related toxicity and resistance. Herein, we report that tobramycin homodimer, a nonribosomal aminoglycoside derivative, potentiates the activities of ceftolozane versus MDR/XDR P. aeruginosa in vitro and delays the emergence of resistance to ceftolozane-tazobactam in the wild-type PAO1 strain. This combination is also more potent than a standard ceftazidime-avibactam combination against these isolates. Conversely, a tobramycin monomer with intrinsic ribosomal properties does not potentiate ceftolozane under similar conditions. Susceptibility and checkerboard studies were assessed using serial 2-fold dilution assays, following the Clinical and Laboratory Standards Institute (CLSI) guidelines. This strategy provides an avenue to further preserve the clinical utility of ceftolozane and enhances its spectrum of activity against one of the most difficult-to-treat pathogens in hospitals.

scholarly journals OligoG CF-5/20 Disruption of Mucoid Pseudomonas aeruginosa Biofilm in a Murine Lung Infection Model

2016 ◽  
Vol 60 (5) ◽  
pp. 2620-2626 ◽  
Author(s):  
Wang Hengzhuang ◽  
Zhijun Song ◽  
Oana Ciofu ◽  
Edvar Onsøyen ◽  
Philip D. Rye ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Infection Model ◽  
Dependent Manner ◽  
Clinical Value ◽  
Biofilm Growth ◽  
Content Type ◽  
Log Reduction

ABSTRACTBiofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used bothin vitrominimum biofilm eradication concentration (MBEC) assays and anin vivomodel of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF-5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate ofPseudomonas aeruginosaembedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose-dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore,in vitroassays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 μg/ml to 4 μg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections.

scholarly journals Phage Therapy: a Step Forward in the Treatment of Pseudomonas aeruginosa Infections

2015 ◽  
Vol 89 (15) ◽  
pp. 7449-7456 ◽  
Author(s):  
Diana P. Pires ◽  
Diana Vilas Boas ◽  
Sanna Sillankorva ◽  
Joana Azeredo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Therapeutic Strategy ◽  
Phage Therapy ◽  
Content Type ◽  
Common Causes ◽  
Health Care Associated Infections ◽  
Common Infection

Antimicrobial resistance constitutes one of the major worldwide public health concerns. Bacteria are becoming resistant to the vast majority of antibiotics, and nowadays, a common infection can be fatal. To address this situation, the use of phages for the treatment of bacterial infections has been extensively studied as an alternative therapeutic strategy. SincePseudomonas aeruginosais one of the most common causes of health care-associated infections, many studies have reported thein vitroandin vivoantibacterial efficacy of phage therapy against this bacterium. This review collects data of all theP. aeruginosaphages sequenced to date, providing a better understanding about their biodiversity. This review further addresses thein vitroandin vivoresults obtained by using phages to treat or preventP. aeruginosainfections as well as the major hurdles associated with this therapy.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals In VitroAntibacterial Activity of NB-003 against Propionibacterium acnes

2011 ◽  
Vol 55 (9) ◽  
pp. 4211-4217 ◽  
Author(s):  
J. Pannu ◽  
A. McCarthy ◽  
A. Martin ◽  
T. Hamouda ◽  
S. Ciotti ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Propionibacterium Acnes ◽  
Resistant Mutant ◽  
Microtiter Plate ◽  
Content Type ◽  
Oil In Water ◽  
Complete Disruption ◽  
Kinetics Of ◽  
Gel Formulations

ABSTRACTNB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections.In vitrosusceptibility ofPropionibacterium acnesto NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against allP. acnesisolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC90s/minimum bactericidal concentrations (MBC90s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 μg/ml, respectively. In the presence of 50% sebum, the MIC90s/MBC90s of NB003 and BPOs increased to 128/1,024 and 400/1,600 μg/ml, respectively. The MIC90s/MBC90s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC90s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC90s/MBC90s of 128/256 μg/ml for NB003 and 214/428 μg/ml for BPO. The addition of EDTA enhanced thein vitroefficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16- and >256-fold decrease in MIC90and MBC90, yielding a more potent MIC90/MBC90of ≤1/<1 μg/ml. The kinetics of bactericidal activity of NB-003 againstP. acneswere compared to those of a commercially available product of BPO. Electron micrographs ofP. acnestreated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance ofP. acnesrevealed no stably resistant mutant strains.

scholarly journals Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistant Mutant ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Content Type ◽  
E Coli ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
The Impact

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.

scholarly journals Bacteriocins of Non-aureus Staphylococci Isolated from Bovine Milk

2017 ◽  
Vol 83 (17) ◽  
Author(s):  
Domonique A. Carson ◽  
Herman W. Barkema ◽  
Sohail Naushad ◽  
Jeroen De Buck
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Genome Mining ◽  
Bovine Milk ◽  
Gene Clusters ◽  
Antibiotic Use ◽  
Content Type ◽  
Treatment And Prevention ◽  
Whole Genomes

ABSTRACT Non-aureus staphylococci (NAS), the bacteria most commonly isolated from the bovine udder, potentially protect the udder against infection by major mastitis pathogens due to bacteriocin production. In this study, we determined the inhibitory capability of 441 bovine NAS isolates (comprising 26 species) against bovine Staphylococcus aureus. Furthermore, inhibiting isolates were tested against a human methicillin-resistant S. aureus (MRSA) isolate using a cross-streaking method. We determined the presence of bacteriocin clusters in NAS whole genomes using genome mining tools, BLAST, and comparison of genomes of closely related inhibiting and noninhibiting isolates and determined the genetic organization of any identified bacteriocin biosynthetic gene clusters. Forty isolates from 9 species (S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. saprophyticus, S. sciuri, S. simulans, S. warneri, and S. xylosus) inhibited growth of S. aureus in vitro, 23 isolates of which, from S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. simulans, and S. xylosus, also inhibited MRSA. One hundred five putative bacteriocin gene clusters encompassing 6 different classes (lanthipeptides, sactipeptides, lasso peptides, class IIa, class IIc, and class IId) in 95 whole genomes from 16 species were identified. A total of 25 novel bacteriocin precursors were described. In conclusion, NAS from bovine mammary glands are a source of potential bacteriocins, with >21% being possible producers, representing potential for future characterization and prospective clinical applications. IMPORTANCE Mastitis (particularly infections caused by Staphylococcus aureus) costs Canadian dairy producers $400 million/year and is the leading cause of antibiotic use on dairy farms. With increasing antibiotic resistance and regulations regarding use, there is impetus to explore bacteriocins (bacterially produced antimicrobial peptides) for treatment and prevention of bacterial infections. We examined the ability of 441 NAS bacteria from Canadian bovine milk samples to inhibit growth of S. aureus in the laboratory. Overall, 9% inhibited growth of S. aureus and 58% of those also inhibited MRSA. In NAS whole-genome sequences, we identified >21% of NAS as having bacteriocin genes. Our study represents a foundation to further explore NAS bacteriocins for clinical use.

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