scholarly journals Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii Using Engineered Quorum-Quenching Lactonases

2013 ◽  
Vol 58 (3) ◽  
pp. 1802-1805 ◽  
Author(s):  
Jeng Yeong Chow ◽  
Yuanyong Yang ◽  
Song Buck Tay ◽  
Kim Lee Chua ◽  
Wen Shan Yew
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Directed Evolution ◽  
Nosocomial Infections ◽  
Biofilm Formation ◽  
Quorum Quenching ◽  
Multidrug Resistant ◽  
Human Pathogen ◽  
Content Type ◽  
Biofilm Disruption

ABSTRACTAcinetobacter baumanniiis a major human pathogen associated with multidrug-resistant nosocomial infections; its virulence is attributed to quorum-sensing-mediated biofilm formation, and disruption of biofilm formation is an attractive antivirulence strategy. Here, we report the first successful demonstration of biofilm disruption in a clinical isolate ofA. baumanniiS1, using a quorum-quenching lactonase obtained by directed evolution; this engineered lactonase significantly reduced the biomass ofA. baumannii-associated biofilms, demonstrating the utility of this antivirulence strategy.

scholarly journals Aerosolized Hypertonic Saline Hinders Biofilm Formation to Enhance Antibiotic Susceptibility of Multidrug-Resistant Acinetobacter baumannii

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1115
Author(s):  
Hui-Ling Lin ◽  
Chen-En Chiang ◽  
Mei-Chun Lin ◽  
Mei-Lan Kau ◽  
Yun-Tzu Lin ◽  
...  
Keyword(s):  
Particle Size ◽  
Particle Size Distribution ◽  
Acinetobacter Baumannii ◽  
Hypertonic Saline ◽  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
Therapeutic Strategy ◽  
Extracellular Polymeric Substances ◽  
Multidrug Resistant ◽  
Biofilm Disruption

Limited therapeutic options are available for multidrug-resistant Acinetobacter baumannii (MDR-AB), and the development of effective treatments is urgently needed. The efficacy of four aerosolized antibiotics (gentamicin, amikacin, imipenem, and meropenem) on three different MDR-AB strains was evaluated using hypertonic saline (HS, 7 g/100 mL) as the aerosol carrier. HS aerosol effectively hindered biofilm formation by specific MDR-AB strains. It could also interrupt the swarming dynamics of MDR-AB and the production of extracellular polymeric substances, which are essential for biofilm progression. Biofilms protect the microorganisms from antibiotics. The use of HS aerosol as a carrier resulted in a decreased tolerance to gentamicin and amikacin in the biofilm-rich MDR-AB. Moreover, we tested the aerosol characteristics of antibiotics mixed with HS and saline, and results showed that HS enhanced the inhaled delivery dose with a smaller particle size distribution of the four antibiotics. Our findings demonstrate the potential of using “old” antibiotics with our “new” aerosol carrier, and potentiate an alternative therapeutic strategy to eliminate MDR-AB infections from a biofilm-disruption perspective.

scholarly journals CsrA Coordinates Compatible Solute Synthesis in Acinetobacter baumannii and Facilitates Growth in Human Urine

2021 ◽  
Author(s):  
Josephine Joy Hubloher ◽  
Kim Schabacker ◽  
Volker Müller ◽  
Beate Averhoff
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Compatible Solute ◽  
Human Pathogen ◽  
Content Type ◽  
Clinical Environments ◽  
Resistant Strains ◽  
Opportunistic Human Pathogen ◽  
Mrna Binding ◽  
Optimal Adaptation

The opportunistic human pathogen Acinetobacter baumannii has become one of the leading causes of nosocomial infections around the world due to the increasing prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. Recently, it was found that CsrA, a global mRNA binding posttranscriptional regulator, plays a role in osmotic stress adaptation, virulence, and growth on amino acids of A. baumannii AB09-003 and 17961.

scholarly journals Biofilm Formation and Quorum-Sensing-Molecule Production by Clinical Isolates of Serratia liquefaciens

2015 ◽  
Vol 81 (10) ◽  
pp. 3306-3315 ◽  
Author(s):  
Sara Remuzgo-Martínez ◽  
María Lázaro-Díez ◽  
Celia Mayer ◽  
Maitane Aranzamendi-Zaldumbide ◽  
Daniel Padilla ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Quorum Sensing ◽  
Nosocomial Infections ◽  
Biofilm Formation ◽  
Acyl Chain ◽  
Homoserine Lactone ◽  
Hospital Environment ◽  
Term Survival ◽  
Content Type ◽  
Serratia Liquefaciens

ABSTRACTSerratiaspp. are opportunistic human pathogens responsible for an increasing number of nosocomial infections. However, little is known about the virulence factors and regulatory circuits that may enhance the establishment and long-term survival ofSerratia liquefaciensin the hospital environment. In this study, two reporter strains,Chromobacterium violaceumCV026 and VIR24, and high-resolution triple-quadrupole liquid chromatography–mass spectrometry (LC-MS) were used to detect and to quantifyN-acyl-homoserine lactone (AHL) quorum-sensing signals in 20S. liquefaciensstrains isolated from clinical samples. Only four of the strains produced sufficient amounts of AHLs to activate the sensors. Investigation of two of the positive strains by high-performance liquid chromatography (HPLC)-MS confirmed the presence of significant amounts of short-acyl-chain AHLs (N-butyryl-l-homoserine lactone [C4-HSL] andN-hexanoyl-l-homoserine lactone [C6-HSL]) in both strains, which exhibited a complex and strain-specific signal profile that included minor amounts of other short-acyl-chain AHLs (N-octanoyl-l-homoserine lactone [C8-HSL] andN-3-oxohexanoyl-l-homoserine lactone [OC6-HSL]) and long-acyl-chain (C10, C12, and C14) AHLs. No correlation between biofilm formation and the production of large amounts of AHLs could be established. Fimbria-like structures were observed by transmission electron microscopy, and the presence of the type 1 fimbrial adhesin genefimHin all strains was confirmed by PCR. The ability ofS. liquefaciensto adhere to abiotic surfaces and to form biofilms likely contributes to its persistence in the hospital environment, increasing the probability of causing nosocomial infections. Therefore, a better understanding of the adherence properties of this species will provide greater insights into the diseases it causes.

scholarly journals Molecular Analysis of the Acinetobacter baumannii Biofilm-Associated Protein

2013 ◽  
Vol 79 (21) ◽  
pp. 6535-6543 ◽  
Author(s):  
H. M. Sharon Goh ◽  
Scott A. Beatson ◽  
Makrina Totsika ◽  
Danilo G. Moriel ◽  
Minh-Duy Phan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Biofilm Growth ◽  
Content Type ◽  
Amino Acid Region ◽  
Carbapenem Resistant ◽  
C Terminus ◽  
And Function

ABSTRACTAcinetobacter baumanniiis a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability ofA. baumanniito survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of theA. baumanniibiofilm-associated protein (Bap) in 24 carbapenem-resistantA. baumanniiST92 strains isolated from a single institution over a 10-year period. Thebapgene was highly prevalent, with 22/24 strains being positive forbapby PCR. Partial sequencing ofbapwas performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that BapMS1968clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, thebapMS1968gene was cloned, and its expression in a recombinantEscherichia colistrain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority ofA. baumanniistrains expressed an ∼200-kDa Bap protein. Further analysis of three Bap-positiveA. baumanniistrains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth byA. baumanniiclinical isolates.

scholarly journals Blue light directly modulates the quorum network in the human pathogen Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marisel Romina Tuttobene ◽  
Gabriela Leticia Müller ◽  
Lucía Blasco ◽  
Natalia Arana ◽  
Mónica Hourcade ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Blue Light ◽  
Therapeutic Potential ◽  
Quorum Quenching ◽  
Human Pathogen ◽  
Independent Manner ◽  
Collective Behaviors ◽  
Promising Strategy ◽  
Environmental Temperatures

AbstractQuorum sensing modulates bacterial collective behaviors including biofilm formation, motility and virulence in the important human pathogen Acinetobacter baumannii. Disruption of quorum sensing has emerged as a promising strategy with important therapeutic potential. In this work, we show that light modulates the production of acyl-homoserine lactones (AHLs), which were produced in higher levels in the dark than under blue light at environmental temperatures, a response that depends on the AHL synthase, AbaI, and on the photoreceptor BlsA. BlsA interacts with the transcriptional regulator AbaR in the dark at environmental temperatures, inducing abaI expression. Under blue light, BlsA does not interact with AbaR, but induces expression of the lactonase aidA and quorum quenching, consistently with lack of motility at this condition. At temperatures found in warm-blooded hosts, the production of AHLs, quorum quenching as well as abaI and aidA expression were also modulated by light, though in this case higher levels of AHLs were detected under blue light than in the dark, in a BlsA-independent manner. Finally, AbaI reduces A. baumannii's ability to kill C. albicans only in the dark both at environmental as well as at temperatures found in warm-blooded hosts. The overall data indicate that light directly modulates quorum network in A. baumannii.

scholarly journals Blue Light Directly Modulates the Quorum Network in the Human Pathogen Acinetobacter baumannii

2021 ◽  
Author(s):  
Marisel Romina Tuttobene ◽  
Gabriela Leticia Müller ◽  
Lucía Blasco ◽  
Lautaro Diacovich ◽  
Pamela Cribb ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Blue Light ◽  
Therapeutic Potential ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Human Pathogen ◽  
Independent Manner ◽  
Collective Behaviors ◽  
Environmental Temperatures

Abstract Quorum sensing modulates bacterial collective behaviors including biofilm formation, motility and virulence in the important human pathogen Acinetobacter baumannii. Disruption of quorum sensing has emerged as a promising strategy with important therapeutic potential. In this work, we show that light modulates the production of secreted molecules that complement motility in the acyl-homoserine lactone (AHL) synthase mutant, abaI, at environmental temperatures. Also, AHLs were produced in higher levels in the dark than under blue light at environmental temperatures, a response that depends on AbaI and on the photoreceptor BlsA. BlsA interacts with the transcriptional regulator AbaR in the dark at environmental temperatures, inducing abaI expression. Under blue light, BlsA does not interact with AbaR, but induces expression of the lactonase aidA and quorum quenching, consistently with lack of motility at this condition. At temperatures found in warm-blooded hosts, the production of AHLs, quorum quenching as well as abaI and aidA expression were also modulated by light in a BlsA-independent manner. Finally, AbaI reduces A. baumannii's ability to kill C. albicans only in the dark both at environmental as well as at temperatures found in warm-blooded hosts. The overall data indicate that light directly modulates quorum network in A. baumannii.

scholarly journals Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate

2015 ◽  
Vol 60 (3) ◽  
pp. 1370-1376 ◽  
Author(s):  
Ghulam Nasser Dhabaan ◽  
Sazaly AbuBakar ◽  
Gustavo Maia Cerqueira ◽  
Mohammed Al-Haroni ◽  
Sui Ping Pang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Clinical Success ◽  
Multidrug Resistant ◽  
Type Iv Pili ◽  
Control Measures ◽  
Content Type ◽  
Type Iv ◽  
Abiotic Surfaces ◽  
Colonization Factors

Acinetobacter baumanniihas emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential forA. baumanniiadherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Impr) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imps) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imprbut not in the Impsisolate. Notably, this finding is corroborated by an increase in the motility of the Imprstrain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage toA. baumanniiand may contribute to clinical success.

scholarly journals Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains

2013 ◽  
Vol 58 (3) ◽  
pp. 1622-1629 ◽  
Author(s):  
Ramamourthy Gopal ◽  
Young Gwon Kim ◽  
Jun Ho Lee ◽  
Seog Ki Lee ◽  
Jeong Don Chae ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Synergistic Effects ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Antibacterial Effects ◽  
Content Type ◽  
Chimeric Peptides ◽  
Novel Antibiotics

ABSTRACTThe increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested againstAcinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. NineteenA. baumanniistrains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC = 3.12 to 12.5 μM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect againstA. baumanniibiofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

scholarly journals A Novel Quorum-Quenching N-Acylhomoserine Lactone Acylase from Acidovorax sp. Strain MR-S7 Mediates Antibiotic Resistance

2017 ◽  
Vol 83 (13) ◽  
Author(s):  
Hiroyuki Kusada ◽  
Hideyuki Tamaki ◽  
Yoichi Kamagata ◽  
Satoshi Hanada ◽  
Nobutada Kimura
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Quorum Quenching ◽  
Multidrug Resistant ◽  
Bifunctional Enzyme ◽  
Content Type ◽  
Acylhomoserine Lactone ◽  
Multidrug Resistant Bacterium

ABSTRACT N-Acylhomoserine lactone acylase (AHL acylase) is a well-known enzyme responsible for disrupting cell-cell communication (quorum sensing) in bacteria. Here, we isolated and characterized a novel and unique AHL acylase (designated MacQ) from a multidrug-resistant bacterium, Acidovorax sp. strain MR-S7. The purified MacQ protein heterologously expressed in Escherichia coli degraded a wide variety of AHLs, ranging from C6 to C14 side chains with or without 3-oxo substitutions. We also observed that AHL-mediated virulence factor production in a plant pathogen, Pectobacterium carotovorum, was dramatically attenuated by coculture with MacQ-overexpressing Escherichia coli, whereas E. coli with an empty vector was unable to quench the pathogenicity, which strongly indicates that MacQ can act in vivo as a quorum-quenching enzyme and interfere with the quorum-sensing system in the pathogen. In addition, this enzyme was found to be capable of degrading a wide spectrum of β-lactams (penicillin G, ampicillin, amoxicillin, carbenicillin, cephalexin, and cefadroxil) by deacylation, clearly indicating that MacQ is a bifunctional enzyme that confers both quorum quenching and antibiotic resistance on strain MR-S7. MacQ has relatively low amino acid sequence identity to any of the known acylases (<39%) and has among the broadest substrate range. Our findings provide the possibility that AHL acylase genes can be an alternative source of antibiotic resistance genes posing a threat to human health if they migrate and transfer to pathogenic bacteria. IMPORTANCE N-Acylhomoserine lactones (AHLs) are well-known signal molecules for bacterial cell-cell communication (quorum sensing), and AHL acylase, which is able to degrade AHLs, has been recognized as a major target for quorum-sensing interference (quorum quenching) in pathogens. In this work, we succeeded in isolating a novel AHL acylase (MacQ) from a multidrug-resistant bacterium and demonstrated that the MacQ enzyme could confer multidrug resistance as well as quorum quenching on the host organism. Indeed, the purified MacQ protein was found to be bifunctional and capable of degrading not only various AHL derivatives but also multiple β-lactam antibiotics by deacylation activities. Although quorum quenching and antibiotic resistance have been recognized to be distinct biological functions, our findings clearly link the two functions by discovering the novel bifunctional enzyme and further providing the possibility that a hitherto-overlooked antibiotic resistance mechanism mediated by the quorum-quenching enzyme may exist in natural environments and perhaps in clinical settings.

scholarly journals Draft Genome Sequences of Three Human Pathogenic Acinetobacter baumannii Strains

2019 ◽  
Vol 8 (14) ◽  
Author(s):  
Masoumeh Madhi ◽  
Troels Ronco ◽  
Alka Hasani ◽  
Rikke H. Olsen
Keyword(s):  
Intensive Care ◽  
Acinetobacter Baumannii ◽  
Intensive Care Units ◽  
Nosocomial Infections ◽  
Draft Genome ◽  
Human Pathogen ◽  
Genome Sequences ◽  
Content Type ◽  
Opportunistic Human Pathogen

Acinetobacter baumannii is an opportunistic human pathogen with the ability to develop multiple resistances against the main antibiotic classes. It causes nosocomial infections, especially in intensive care units.

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