Reservoirs of resistance: polymyxin resistance in veterinary-associated companion animal isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 185 (7) ◽  
pp. 206-206 ◽  
Author(s):  
Andrea Scott ◽  
Sian Pottenger ◽  
Dorina Timofte ◽  
Matthew Moore ◽  
Laura Wright ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Respiratory Infections ◽  
Companion Animals ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Potential Reservoir ◽  
Human Infections ◽  
Animal Isolates

BackgroundPseudomonas aeruginosa is an opportunistic pathogen and a major cause of infections. Widespread resistance in human infections are increasing the use of last resort antimicrobials such as polymyxins. However, these have been used for decades in veterinary medicine. Companion animals are an understudied source of antimicrobial resistant P. aeruginosa isolates. This study evaluated the susceptibility of P. aeruginosa veterinary isolates to polymyxins to determine whether the veterinary niche represents a potential reservoir of resistance genes for pathogenic bacteria in both animals and humans.Methods and resultsClinical P. aeruginosa isolates (n=24) from UK companion animals were compared for antimicrobial susceptibility to a panel of human-associated isolates (n=37). Minimum inhibitory concentration (MIC) values for polymyxin B and colistin in the companion animals was significantly higher than in human isolates (P=0.033 and P=0.013, respectively). Genotyping revealed that the veterinary isolates were spread throughout the P. aeruginosa population, with shared array types from human infections such as keratitis and respiratory infections, suggesting the potential for zoonotic transmission. Whole genome sequencing revealed mutations in genes associated with polymyxin resistance and other antimicrobial resistance-related genes.ConclusionThe high levels of resistance to polymyxin shown here, along with genetic similarities between some human and animal isolates, together suggest a need for sustained surveillance of this veterinary niche as a potential reservoir for resistant, clinically relevant bacteria in both animals and humans.

Pseudomonas aeruginosa Oligoribonuclease Controls Susceptibility to Polymyxin B by Regulating Pel Exopolysaccharide Production

2022 ◽  
Author(s):  
Baopeng Yang ◽  
Yujun Jiang ◽  
Yongxin Jin ◽  
Fang Bai ◽  
Zhihui Cheng ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Resistance ◽  
Defense Mechanism ◽  
Extracellular Polysaccharide ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Guanosine Monophosphate ◽  
Extracellular Dna ◽  
Bacterial Cells ◽  
Bacterial Survival

Polymyxins are considered as the last resort antibiotics to treat infections caused by multidrug-resistant Gram negative pathogens. Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections in humans. Proteins involved in lipopolysaccharide modification and maintaining inner and outer membrane integrities have been found to contribute to the bacterial resistance to polymyxins. Oligoribonuclease (Orn) is an exonuclease that regulates the homeostasis of intracellular (3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), thereby regulating the production of extracellular polysaccharide in P. aeruginosa . Previously, we demonstrated that Orn affects the bacterial resistance to fluoroquinolone, β-lactam and aminoglycoside antibiotics. In this study, we found that mutation of orn increased the bacterial survival following polymyxin B treatment in a wild type P. aeruginosa strain PA14. Overexpression of c-di-GMP degradation enzymes in the orn mutant reduced the bacterial survival. By using a fluorescence labeled polymyxin B, we found that mutation of orn increased the bacterial surface bound polymyxin B. Deletion of the Pel synthesis genes or treatment with a Pel hydrolase reduced the surface bound polymyxin B and bacterial survival. We further demonstrated that Pel binds to extracellular DNA (eDNA), which traps polymyxin B and thus protects the bacterial cells. Collectively, our results revealed a novel defense mechanism against polymyxin in P. aeruginosa .

scholarly journals F-type Pyocins are Diverse Non-Contractile Phage Tail-Like Weapons for Killing Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Senjuti Saha ◽  
Chidozie D. Ojobor ◽  
Erik Mackinnon ◽  
Olesia I. North ◽  
Joseph Bondy-Denomy ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Pathogenic Bacteria ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Genes Encoding ◽  
Intraspecies Competition

ABSTRACTMost Pseudomonas aeruginosa strains produce bacteriocins derived from contractile or non-contractile phage tails known as R-type and F-type pyocins, respectively. These bacteriocins possess strain-specific bactericidal activity against P. aeruginosa and likely increase evolutionary fitness through intraspecies competition. R-type pyocins have been studied extensively and show promise as alternatives to antibiotics. Although they have similar therapeutic potential, experimental studies on F-type pyocins are limited. Here, we provide a bioinformatic and experimental investigation of F-type pyocins. We introduce a systematic naming scheme for genes found in R- and F-type pyocin operons and identify 15 genes invariably found in strains producing F-type pyocins. Five proteins encoded at the 3’-end of the F-type pyocin cluster are divergent in sequence, and likely determine bactericidal specificity. We use sequence similarities among these proteins to define 11 distinct F-type pyocin groups, five of which had not been previously described. The five genes encoding the variable proteins associate in two modules that have clearly re-assorted independently during the evolution of these operons. These proteins are considerably more diverse than the specificity-determining tail fibers of R-type pyocins, suggesting that F-type pyocins emerged earlier or have been subject to distinct evolutionary pressures. Experimental studies on six F-type pyocin groups show that each displays a distinct spectrum of bactericidal activity. This activity is strongly influenced by the lipopolysaccharide O-antigen type, but other factors also play a role. F-type pyocins appear to kill as efficiently as R-type pyocins. These studies set the stage for the development of F-type pyocins as anti-bacterial therapeutics.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen that causes a broad spectrum of antibiotic resistant infections with high mortality rates, particularly in immunocompromised individuals and cystic fibrosis patients. Due to the increasing frequency of multidrug-resistant P. aeruginosa infections, there is great interest in the development of alternative therapeutics. One alternative is protein-based antimicrobials called bacteriocins, which are produced by one strain of bacteria to kill other strains. In this study, we investigate F-type pyocins, bacteriocins naturally produced by P. aeruginosa that resemble non-contractile phage tails. We show that they are potent killers of P. aeruginosa, and distinct pyocin groups display different killing specificities. We have identified the probable specificity determinants of F-type pyocins, which opens up the potential to engineer them to precisely target strains of pathogenic bacteria. The resemblance of F-type pyocins to well characterized phage tails will greatly facilitate their development into effective antibacterials.

scholarly journals Light Modulates Important Pathogenic Determinants and Virulence in Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus ESKAPE Pathogens

2020 ◽  
Author(s):  
M. R. Tuttobene ◽  
J. F. Pérez ◽  
E. Pavesi ◽  
B. Perez Mora ◽  
D. Biancotti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
General Concept ◽  
Infection Model ◽  
Type Vi Secretion System ◽  
Sense And Respond ◽  
Human Infections

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that ESKAPE priority pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility and growth under iron deprived conditions are modulated by light in S. aureus. Light also regulates persistence, metabolism and the ability to kill competitors, in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, though the response is not the same in the different species: virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) are involved in virulence modulation by light in A. baumannii. Overall, this fundamental knowledge highlights the potential use of light to control pathogen's virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration. IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease: in the presence of light some of them become more aggressive while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to control infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

scholarly journals Poly (acetyl arginyl) glucosamine attenuates Pseudomonas aeruginosa in a rat lung infection model

2021 ◽  
Author(s):  
Bryan Garcia ◽  
Melissa S. McDaniel ◽  
Allister J. Loughran ◽  
J. Dixon Johns ◽  
Vidya Narayanaswamy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Respiratory Infections ◽  
Bacterial Species ◽  
Membrane Integrity ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Total Biomass ◽  
Chronic Infections

Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer which has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity which can normalize rheologic properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, which may warrant further evaluation as a therapeutic.

scholarly journals Caspofungin and Polymyxin B Reduce the Cell Viability and Total Biomass of Mixed Biofilms of Carbapenem-Resistant Pseudomonas aeruginosa and Candida spp.

2020 ◽  
Vol 11 ◽  
Author(s):  
Luciana Fernandes ◽  
Bruna Nakanishi Fortes ◽  
Nilton Lincopan ◽  
Kelly Ishida
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Activity ◽  
Inhibitory Concentration ◽  
Polymyxin B ◽  
Antibiofilm Activity ◽  
Total Biomass ◽  
Planktonic Cells ◽  
Carbapenem Resistant ◽  
Cell Counts ◽  
Viable Cells

Pseudomonas aeruginosa and Candida spp. are biofilm-forming pathogens commonly found colonizing medical devices, being mainly associated with pneumonia and bloodstream infections. The coinfection by these pathogens presents higher mortality rates when compared to those caused by a single microbial species. This study aimed to evaluate the antibiofilm activity of echinocandins and polymyxin B (PMB) against polymicrobial biofilms of carbapenem-resistant (CR) Pseudomonas aeruginosa and Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata). In addition, we tested the antimicrobial effect on their planktonic and monomicrobial biofilm counterparties. Interestingly, beyond inhibition of planktonic [minimum inhibitory concentration (MIC) = 0.5 μg/ml] and biofilm [minimum biofilm inhibitory concentration (MBIC)50 ≤ 2–8 μg/ml] growth of P. aeruginosa, PMB was also effective against planktonic cells of C. tropicalis (MIC = 2 μg/ml), and polymicrobial biofilms of CR P. aeruginosa with C. tropicalis (MBIC50 ≤ 2 μg/ml), C. parapsilosis (MBIC50 = 4–16 μg/ml), C. glabrata (MBIC50 = 8–16 μg/ml), or C. albicans (MBIC50 = 8–64 μg/ml). On the other hand, while micafungin (MFG) showed highest inhibitory activity against planktonic (MIC ≤ 0.008–0.5 μg/ml) and biofilm (MBIC50 ≤ 2–16 μg/ml) growth of Candida spp.; caspofungin (CAS) displays inhibitory activity against planktonic cells (MIC = 0.03–0.25 μg/ml) and monomicrobial biofilms (MBIC50 ≤ 2–64 μg/ml) of Candida spp., and notably on planktonic and monomicrobial biofilms of CR P. aeruginosa (MIC or MBIC50 ≥ 64 μg/ml). Particularly, for mixed biofilms, while CAS reduced significantly viable cell counts of CR P. aeruginosa and Candida spp. at ≥32 and ≥ 2 μg/ml, respectively; PMB was effective in reducing viable cells of CR P. aeruginosa at ≥2 μg/ml and Candida spp. at ≥8 μg/ml. Similar reduction of viable cells was observed for CAS (32–64 μg/ml) combined with PMB (2 μg/ml). These findings highlight the potential of PMB and CAS for the treatment of polymicrobial infections caused by Candida spp. and critical priority CR P. aeruginosa.

scholarly journals Prevalence, Virulence, Antimicrobial Resistance, and Molecular Characterization of Pseudomonas aeruginosa Isolates From Drinking Water in China

2020 ◽  
Vol 11 ◽  
Author(s):  
Lei Wei ◽  
Qingping Wu ◽  
Jumei Zhang ◽  
Weipeng Guo ◽  
Qihui Gu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drinking Water ◽  
Antimicrobial Resistance ◽  
Virulence Genes ◽  
Drinking Water Treatment ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Detection Rates ◽  
Water Treatment Process ◽  
Comprehensive Data

Pseudomonas aeruginosa is an important opportunistic pathogen and remains a major threat to the microbial safety of drinking water. There is a lack of comprehensive data on P. aeruginosa contamination in drinking water in China. Therefore, this study aimed to determine the prevalence, genetic diversity, virulence genes, and antimicrobial resistance of P. aeruginosa isolated from mineral water and spring water in China. From January 2013 to January 2014, 314 drinking water samples were collected from 23 cities in China. Of the collected samples, 77 (24.5%) were contaminated with P. aeruginosa, and these comprised 34 raw water (30.4%), 39 activated carbon-filtered water (30.6%), and four final water product (3.9%). A total of 132 P. aeruginosa isolates were obtained, and all of them showed the presence of virulence genes, with the detection rates of ExoU, ExoS, phzM, toxA, and lasB genes being 7.6, 86.3, 95.5, 89.4, and 100%, respectively. All isolates were sensitive to the 14 antibiotics (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, gentamicin, tobramycin, amikacin, polymyxin B, imipenem, meropenem, aztreonam, ceftazidime, cefepime, and piperacillin/tazobactam) tested. The 132 isolates were categorized into 42 sequence types according to multilocus sequence typing, and ST235 accounted for 8.3% (11) of the total isolates. Thus, this study provides comprehensive data on the prevalence and characteristics of P. aeruginosa in drinking water in China and can aid in developing preventive measures against contamination during the drinking water treatment process.

scholarly journals Prevalence and clinical outcomes of episodes of ventilator-associated pneumonia caused by SPM-1-producing and non-producing imipenem-resistant Pseudomonas aeruginosa

2011 ◽  
Vol 44 (5) ◽  
pp. 604-606 ◽  
Author(s):  
Guilherme Henrique Campos Furtado ◽  
Ana Cristina Gales ◽  
Luciana Baria Perdiz ◽  
Anderson Fernandes Santos ◽  
Eduardo Alexandrino Servolo de Medeiros
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Outcomes ◽  
Respiratory Infections ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Ventilator Associated Pneumonia ◽  
Antimicrobial Drugs ◽  
Major Mechanism ◽  
Carbapenem Resistant ◽  
Related Mortality

INTRODUCTION: Pseudomonas aeruginosa is a leading cause of ventilator-associated pneumonia (VAP) and exhibits high rates of resistance to several antimicrobial drugs. The carbapenens are usually the drugs of choice against this microorganism. However, the carbapenem resistance has increased among these strains worldwide. The presence of metallo-β-lactamases (MBL) has been pointed out as a major mechanism of resistance among these strains. No previous study addressed outcomes of respiratory infections caused by these strains. METHODS: Our group sought to analyze the epidemiology and clinical outcomes of patients with VAP caused by imipenem-resistant P. aeruginosa. A total of 29 clinical isolates of carbapenem-resistant Pseudomonas aeruginosa were screened for metallo-β-lactamase (MBL) genes. RESULTS: Demographic and clinical variables were similar between the SPM-1-producing and non-SPM-1-producing group. Five (17.2%) isolates were positive for blaSPM-1. No other MBL gene was found. All patients were treated with polymyxin B. The infection-related mortality was 40% and 54.2% for SPM-1-producing and -non-producing isolates, respectively. CONCLUSIONS: There were no differences in epidemiological and clinical outcomes between the two groups.

Detection of Virulence Factors and Antibiotic Resistance Pattern of Clinical and Intensive Care Unit Environmental Isolates of Pseudomonas aeruginosa

2020 ◽  
Vol 20 (5) ◽  
pp. 758-762
Author(s):  
Omid Zarei ◽  
Hassan Mahmoudi ◽  
Ali Mohammadi Bardbari ◽  
Pezhman Karami ◽  
Mohammad Yousef Alikhani
Keyword(s):  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Intensive Care ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Diffusion Method ◽  
Resistance Pattern ◽  
Disk Diffusion Method ◽  
Human Infections

Background: Pseudomonas aeruginosa is a gram-negative non-glucose fermenting aerobic bacteria and an opportunistic pathogen in humans and animals. The present study was carried out to investigate the distribution of virulence factors and antibiotic resistance properties of P. aeruginosa isolated from patients and intensive care unit (ICU) environment. Material and Methods: A total of 116 P. aeruginosa isolated from patients and ICU environment were collected from Besat hospital in Hamadan, the West of Iran. P. aeruginosa isolates were analyzed based on the presence of the virulence factors encoding genes included exoA, exoS, exoU, and algD using polymerase chain reaction (PCR). Antimicrobial susceptibility test was performed using a disk diffusion method. Results: The results showed the prevalence of exoA 33 (56.9%), exoS 21 (36.20%), exoU 37 (63.8%), and algD 35 (60.34%) genes in ICU environment P. aeruginosa strains and exo A 23 (39.25%), exoS 25 (43.1%), exoU 40(68.98%), and algD 25 (43.1%) genes in clinical isolates of P. aeruginosa. High resistance levels of the clinical and ICU environment isolate to ampicillinsulbactam (100%), were also observed. Conclusions: Our findings should raise awareness about antibiotic resistance in hospitalized patients in Iran. Clinicians should exercise caution in prescribing antibiotics, especially in cases of human infections.

scholarly journals In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 101 ◽  
Author(s):  
Nagaia Ciacci ◽  
Selene Boncompagni ◽  
Felice Valzano ◽  
Lisa Cariani ◽  
Stefano Aliberti ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Respiratory Infections ◽  
Topical Administration ◽  
Opportunistic Pathogen ◽  
Wide Range ◽  
Tract Infections ◽  
Human Infections ◽  
Time Kill ◽  
Dose Dependent

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 µg/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time–kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further.

scholarly journals The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 2120-2132 ◽  
Author(s):  
Olivier M. Vandeputte ◽  
Martin Kiendrebeogo ◽  
Tsiry Rasamiravaka ◽  
Caroline Stévigny ◽  
Pierre Duez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Gene Products ◽  
Strain Pao1 ◽  
Preliminary Screening ◽  
Mutant Strains

Preliminary screening of the Malagasy plant Combretum albiflorum for compounds attenuating the production of quorum sensing (QS)-controlled virulence factors in bacteria led to the identification of active fractions containing flavonoids. In the present study, several flavonoids belonging to the flavone, flavanone, flavonol and chalcone structural groups were screened for their capacity to reduce the production of QS-controlled factors in the opportunistic pathogen Pseudomonas aeruginosa (strain PAO1). Flavanones (i.e. naringenin, eriodictyol and taxifolin) significantly reduced the production of pyocyanin and elastase in P. aeruginosa without affecting bacterial growth. Consistently, naringenin and taxifolin reduced the expression of several QS-controlled genes (i.e. lasI, lasR, rhlI, rhlR, lasA, lasB, phzA1 and rhlA) in P. aeruginosa PAO1. Naringenin also dramatically reduced the production of the acylhomoserine lactones N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL), which is driven by the lasI and rhlI gene products, respectively. In addition, using mutant strains deficient for autoinduction (ΔlasI and ΔrhlI) and LasR- and RhlR-based biosensors, it was shown that QS inhibition by naringenin not only is the consequence of a reduced production of autoinduction compounds but also results from a defect in the proper functioning of the RlhR–C4-HSL complex. Widely distributed in the plant kingdom, flavonoids are known for their numerous and determinant roles in plant physiology, plant development and in the success of plant–rhizobia interactions, but, as shown here, some of them also have a role as inhibitors of the virulence of pathogenic bacteria by interfering with QS mechanisms.

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