scholarly journals Acinetobacter baumannii Quorum sensing: A way to communicate and a target to eradicate

2021 ◽  
Vol 3 (2) ◽  
pp. 134-145
Author(s):  
Elkheloui Raja ◽  
Hamadi Fatima ◽  
Mimouni Rachida
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Chronic Infections ◽  
New Strategy

Quorum sensing is a communication system based on the actions of chemical signal molecules depending on the density of the cell population. These molecules are widely considered as effectors of the gene expression of several virulence factors. As a result, it has attracted a lot of attention because of its possible applicability as a target for treating infections. This review attempts to give a description of this system on gram negative bacteria specifically on Acinetobacter baumannii as an important nosocomial pathogen. Additionally, quorum sensing in biofilm will be also treated because it is considered as the origin of several chronic infections. Numerous studies have been carried out to prove the role of inhibitors in the disruption of quorum sensing, known as quorum quenching. Quorum quenching is a new strategy to eradicate bacterial infections due to the crucial intervention of quorum sensing in different virulence factors and particularly in the biofilm formation.

scholarly journals Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N-Acylhomoserine Lactone Lactonase QsdA

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Franziska S. Birmes ◽  
Ruth Säring ◽  
Miriam C. Hauke ◽  
Niklas H. Ritzmann ◽  
Steffen L. Drees ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Rhodococcus Erythropolis ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Content Type ◽  
Acylhomoserine Lactone ◽  
Regulatory Effects ◽  
Epithelial Lung Cells

ABSTRACT The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in cocultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.

scholarly journals Quenching of acyl-homoserine lactone-dependent quorum sensing by enzymatic disruption of signal molecules.

2009 ◽  
Vol 56 (1) ◽  
Author(s):  
Robert Czajkowski ◽  
Sylwia Jafra
Keyword(s):  
Quorum Sensing ◽  
Pathogenic Bacteria ◽  
Degradation Products ◽  
Antibiotic Production ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Animal Pathogens

Many Gram-positive and Gram-negative bacteria communicate using small diffusible signal molecules called autoinducers. This process, known as quorum sensing (QS), links cell density to the expression of genes as diverse as those associated with virulence factors production of plant and animal pathogens, bioluminescence, antibiotic production, sporulation or biofilm formation. In Gram-negative bacteria, this communication is mainly mediated by N-acyl-homoserine lactones (AHLs). It has been proven that inactivation of the signal molecules attenuates many of the processes controlled by QS. Enzymatic degradation of the signal molecules has been amply described. Two main classes of AHL-inactivating enzymes were identified: AHL lactonases which hydrolyse the lactone ring in AHLs, and AHL acylases (syn. AHL amidases) which liberate a free homoserine lactone and a fatty acid. Recently, AHL oxidoreductase, a novel type of AHL inactivating enzyme, was described. The activity of these enzymes results in silencing the QS-regulated processes, as degradation products cannot act as signal molecules. The ability to inactivate AHL (quorum quenching, QQ) might be useful in controlling virulence of many pathogenic bacteria.

scholarly journals Quorum Sensing Pseudomonas Quinolone Signal Forms Chiral Supramolecular Assemblies With the Host Defense Peptide LL-37

2021 ◽  
Vol 8 ◽  
Author(s):  
Ferenc Zsila ◽  
Maria Ricci ◽  
Imola Csilla Szigyártó ◽  
Priyanka Singh ◽  
Tamás Beke-Somfai
Keyword(s):  
Quorum Sensing ◽  
Host Defense ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Quorum Quenching ◽  
Bacterial Biofilms ◽  
Phenotypic Traits ◽  
Signal Molecules ◽  
Supramolecular Architectures

Host defense antimicrobial peptides (HDPs) constitute an integral component of the innate immune system having nonspecific activity against a broad spectrum of microorganisms. They also have diverse biological functions in wound healing, angiogenesis, and immunomodulation, where it has also been demonstrated that they have a high affinity to interact with human lipid signaling molecules. Within bacterial biofilms, quorum sensing (QS), the vital bacterial cell-to-cell communication system, is maintained by similar diffusible small molecules which control phenotypic traits, virulence factors, biofilm formation, and dispersion. Efficient eradication of bacterial biofilms is of particular importance as these colonies greatly help individual cells to tolerate antibiotics and develop antimicrobial resistance. Regarding the antibacterial function, for several HDPs, including the human cathelicidin LL-37, affinity to eradicate biofilms can exceed their activity to kill individual bacteria. However, related underlying molecular mechanisms have not been explored yet. Here, we employed circular dichroism (CD) and UV/VIS spectroscopic analysis, which revealed that LL-37 exhibits QS signal affinity. This archetypal representative of HDPs interacts with the Pseudomonas quinolone signal (PQS) molecules, producing co-assemblies with peculiar optical activity. The binding of PQS onto the asymmetric peptide chains results in chiral supramolecular architectures consisting of helically disposed, J-aggregated molecules. Besides the well-known bacterial membrane disruption activity, our data propose a novel action mechanism of LL-37. As a specific case of the so-called quorum quenching, QS signal molecules captured by the peptide are sequestered inside co-assemblies, which may interfere with the microbial QS network helping to prevent and eradicate bacterial infections.

High frequency of blaPER-1 gene in clinical strains of Acinetobacter baumannii and its association with quorum sensing and virulence factors

Gene Reports ◽  
2021 ◽  
Vol 24 ◽  
pp. 101232
Author(s):  
Fariba Naeimi Mazraeh ◽  
Alka Hasani ◽  
Javid Sadeghi ◽  
Hossein Samadi Kafil ◽  
Mohammad Hossein Soroush Barhaghi ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
High Frequency ◽  
Clinical Strains

scholarly journals Bacterial Quorum-Quenching Lactonase Hydrolyzes Fungal Mycotoxin and Reduces Pathogenicity of Penicillium expansum—Suggesting a Mechanism of Bacterial Antagonism

2021 ◽  
Vol 7 (10) ◽  
pp. 826
Author(s):  
Shlomit Dor ◽  
Dov Prusky ◽  
Livnat Afriat-Jurnou
Keyword(s):  
Cell Wall ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Recombinant Expression ◽  
Bacterial Species ◽  
Quorum Quenching ◽  
Host Cells ◽  
Penicillium Expansum ◽  
Fungal Colonization

Penicillium expansum is a necrotrophic wound fungal pathogen that secrets virulence factors to kill host cells including cell wall degrading enzymes (CWDEs), proteases, and mycotoxins such as patulin. During the interaction between P. expansum and its fruit host, these virulence factors are strictly modulated by intrinsic regulators and extrinsic environmental factors. In recent years, there has been a rapid increase in research on the molecular mechanisms of pathogenicity in P. expansum; however, less is known regarding the bacteria–fungal communication in the fruit environment that may affect pathogenicity. Many bacterial species use quorum-sensing (QS), a population density-dependent regulatory mechanism, to modulate the secretion of quorum-sensing signaling molecules (QSMs) as a method to control pathogenicity. N-acyl homoserine lactones (AHLs) are Gram-negative QSMs. Therefore, QS is considered an antivirulence target, and enzymes degrading these QSMs, named quorum-quenching enzymes, have potential antimicrobial properties. Here, we demonstrate that a bacterial AHL lactonase can also efficiently degrade a fungal mycotoxin. The mycotoxin is a lactone, patulin secreted by fungi such as P. expansum. The bacterial lactonase hydrolyzed patulin at high catalytic efficiency, with a kcat value of 0.724 ± 0.077 s−1 and KM value of 116 ± 33.98 μM. The calculated specific activity (kcat/KM) showed a value of 6.21 × 103 s−1M−1. While the incubation of P. expansum spores with the purified lactonase did not inhibit spore germination, it inhibited colonization by the pathogen in apples. Furthermore, adding the purified enzyme to P. expansum culture before infecting apples resulted in reduced expression of genes involved in patulin biosynthesis and fungal cell wall biosynthesis. Some AHL-secreting bacteria also express AHL lactonase. Here, phylogenetic and structural analysis was used to identify putative lactonase in P. expansum. Furthermore, following recombinant expression and purification of the newly identified fungal enzyme, its activity with patulin was verified. These results indicate a possible role for patulin and lactonases in inter-kingdom communication between fungi and bacteria involved in fungal colonization and antagonism and suggest that QQ lactonases can be used as potential antifungal post-harvest treatment.

Bacterial Quorum Sensing During Infection

2020 ◽  
Vol 74 (1) ◽  
pp. 201-219 ◽  
Author(s):  
Sheyda Azimi ◽  
Alexander D. Klementiev ◽  
Marvin Whiteley ◽  
Stephen P. Diggle
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Human Infection ◽  
Future Research ◽  
Virulence Determinants ◽  
Plant Laboratory ◽  
Bacterial Quorum Sensing ◽  
Bacterial Quorum

Bacteria are highly interactive and possess an extraordinary repertoire of intercellular communication and social behaviors, including quorum sensing (QS). QS has been studied in detail at the molecular level, so mechanistic details are well understood in many species and are often involved in virulence. The use of different animal host models has demonstrated QS-dependent control of virulence determinants and virulence in several human pathogenic bacteria. QS also controls virulence in several plant pathogenic species. Despite the role QS plays in virulence during animal and plant laboratory-engineered infections, QS mutants are frequently isolated from natural infections, demonstrating that the function of QS during infection and its role in pathogenesis remain poorly understood and are fruitful areas for future research. We discuss the role of QS during infection in various organisms and highlight approaches to better understand QS during human infection. This is an important consideration in an era of growing antimicrobial resistance, when we are looking for new ways to target bacterial infections.

scholarly journals Genetic analysis of surface motility in Acinetobacter baumannii

Microbiology ◽  
2011 ◽  
Vol 157 (9) ◽  
pp. 2534-2544 ◽  
Author(s):  
Katy M. Clemmer ◽  
Robert A. Bonomo ◽  
Philip N. Rather
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Null Allele ◽  
De Novo ◽  
Type Iv ◽  
Lytic Transglycosylase ◽  
Outer Membrane Porin ◽  
Surfactant Production ◽  
Surface Motility

The Gram-negative pathogen Acinetobacter baumannii strain M2 was found to exhibit a robust surface motility on low-percentage (0.2–0.4 %) agar plates. These patterns of motility were dramatically different depending on whether Difco or Eiken agar was used. Motility was observed in many, but not all, clinical and environmental isolates. The use of drop collapse assays to demonstrate surfactant production was unsuccessful, and the role of surfactants in A. baumannii M2 motility remains unclear. Surface motility was impaired by an insertion in pilT, encoding a gene product that is often required for retraction of the type IV pilus. Motility was also dependent on quorum sensing, as a null allele in the abaI autoinducer synthase decreased motility, and the addition of exogenous N-(3-hydroxy)-dodecanoylhomoserine lactone (3-OH C12-HSL) restored motility to the abaI mutant. Transposon mutagenesis was used to identify additional genes required for motility and revealed loci encoding various functions: non-ribosomal synthesis of a putative lipopeptide, a sensor kinase (BfmS), a lytic transglycosylase, O-antigen biosynthesis (RmlB), an outer membrane porin (OmpA) and de novo purine biosynthesis (PurK). Two of the above genes required for motility were highly activated by quorum sensing, and may explain, in part, the requirement for quorum sensing in motility.

scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

scholarly journals PqsE Functions Independently of PqsR-Pseudomonas Quinolone Signal and Enhances the rhl Quorum-Sensing System

2008 ◽  
Vol 190 (21) ◽  
pp. 7043-7051 ◽  
Author(s):  
John M. Farrow ◽  
Zoe M. Sund ◽  
Matthew L. Ellison ◽  
Dana S. Wade ◽  
James P. Coleman ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Chronic Infections ◽  
Signaling Systems ◽  
Sensing System ◽  
Pseudomonas Quinolone Signal ◽  
Quorum Sensing System ◽  
Hostile Environments

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections in immunocompromised individuals. This gram-negative bacterium produces a battery of virulence factors that allow it to infect and survive in many different hostile environments. The control of many of these virulence factors falls under the influence of one of three P. aeruginosa cell-to-cell signaling systems. The focus of this study, the quinolone signaling system, functions through the Pseudomonas quinolone signal (PQS), previously identified as 2-heptyl-3-hydroxy-4-quinolone. This signal binds to and activates the LysR-type transcriptional regulator PqsR (also known as MvfR), which in turn induces the expression of the pqsABCDE operon. The first four genes of this operon are required for PQS synthesis, but the fifth gene, pqsE, is not. The function of the pqsE gene is not known, but it is required for the production of multiple PQS-controlled virulence factors and for virulence in multiple models of infection. In this report, we show that PqsE can activate PQS-controlled genes in the absence of PqsR and PQS. Our data also suggest that the regulatory activity of PqsE requires RhlR and indicate that a pqsE mutant can be complemented for pyocyanin production by a large excess of exogenous N-butyryl homoserine lactone (C4-HSL). Finally, we show that PqsE enhances the ability of Escherichia coli expressing RhlR to respond to C4-HSL. Overall, our data lead us to conclude that PqsE functions as a regulator that is independent of PqsR and PQS but dependent on the rhl quorum-sensing system.

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