Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review

Soheili, Vahid; Tajani, Amineh Sadat; Ghodsi, Razieh; Bazzaz, Bibi Sedigheh Fazly

doi:10.1016/j.ejmech.2019.03.049

Cited by 59 publications

(46 citation statements)

References 51 publications

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“…In clinic therapeutics for infectious diseases, antibiotic resistance has been spreading widely and rapidly, which becomes a major challenge for modern medicine. The strategy of interfering the biofilm formation is effective through bacterial cell-to-cell communication, especially with QS system (Soheili et al, 2019). More recently, QS inhibitors are drawing great attention in blocking the pathogenicity from P. aeruginosa (Calvert et al, 2018; Schütz and Empting, 2018).…”

Section: Resultsmentioning

confidence: 99%

Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa?

Yan

2019

Front. Microbiol.

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Pseudomonas aeruginosa is a Gram-negative bacterium causing diseases in plants, animals, and humans, and its drug resistance is a major concern in medical care. Biofilms play an important role in P. aeruginosa drug resistance. Three factors are most important to induce biofilm: quorum sensing (QS), bis-(3′-5′)-cyclic diguanosine monophosphate (c-di-GMP), and small RNAs (sRNAs). P. aeruginosa has its own specific QS system (PQS) besides two common QS systems, LasI–LasR and RhlI–RhlR, in bacteria. PQS is interesting not only because there is a negative regulation from RhlR to pqsR but also because the null mutation in PQS leads to a reduced biofilm formation. Furthermore, P. aeruginosa dispersed cells have physiological features that are distinct between the planktonic cells and biofilm cells. In response to a low concentration of c-di-GMP, P. aeruginosa cells can disperse from the biofilms to become planktonic cells. These raise an interesting hypothesis of whether biofilm can be reversed through the QS mechanism in P. aeruginosa . Although a single factor is certainly not sufficient to prevent the biofilm formation, it necessarily explores such possibility. In this hypothesis, the literature is analyzed to determine the negative regulation pathways, and then the transcriptomic data are analyzed to determine whether this hypothesis is workable or not. Unexpectedly, the transcriptomic data reveal a negative regulation between lasI and psqR . Also, the individual cases from transcriptomic data demonstrate the negative regulations of PQS with laslI, laslR , rhlI , and rhlR under different experiments. Based on our analyses, possible strategies to reverse biofilm formation are proposed and their clinic implications are addressed.

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Section: Resultsmentioning

confidence: 99%

Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa?

Yan

2019

Front. Microbiol.

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“…Previous studies were aimed at identifying novel antibiotics by targeting the transcriptional machinery of bacteria ( 91 , 92 ). This can include targeting riboswitches ( 66 , 82–84 , 93 ), transcription factors ( 94 , 95 ) or the RNA polymerase itself ( 96 , 97 ). Rifampicin inhibits the bacterial RNAP ( 98 ) by blocking elongation ( 99 ) and is the leading drug to treat mycobacterial infections such as tuberculosis ( 100 ).…”

Section: Resultsmentioning

confidence: 99%

SPRINT: a Cas13a-based platform for detection of small molecules

Iwasaki

Batey

2020

Nucleic Acids Research

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Recent efforts in biological engineering have made detection of nucleic acids in samples more rapid, inexpensive and sensitive using CRISPR-based approaches. We expand one of these Cas13a-based methods to detect small molecules in a one-batch assay. Using SHERLOCK-based profiling of in vitrotranscription (SPRINT), in vitro transcribed RNA sequence-specifically triggers the RNase activity of Cas13a. This event activates its non-specific RNase activity, which enables cleavage of an RNA oligonucleotide labeled with a quencher/fluorophore pair and thereby de-quenches the fluorophore. This fluorogenic output can be measured to assess transcriptional output. The use of riboswitches or proteins to regulate transcription via specific effector molecules is leveraged as a coupled assay that transforms effector concentration into fluorescence intensity. In this way, we quantified eight different compounds, including cofactors, nucleotides, metabolites of amino acids, tetracycline and monatomic ions in samples. In this manner, hundreds of reactions can be easily quantified in a few hours. This increased throughput also enables detailed characterization of transcriptional regulators, synthetic compounds that inhibit transcription, or other coupled enzymatic reactions. These SPRINT reactions are easily adaptable to portable formats and could therefore be used for the detection of analytes in the field or at point-of-care situations.

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“…O sistema pqs (Sinal de quinolona de Pseudomonas) funciona a partir de dois autoindutores, a molécula 2-heptil-3hidroxi-4-quinolona (PQS) (Figura 1) e sua precursora, a molécula 2-heptil-4-quinolona (HHQ) (Gallagher et al, 2002). O pqs é ativado quando o fator transcricional PqsR é estimulado pelos autoindutores HHQ ou PQS, amplificando a expressão do opéron pqsABCDE, onde o quinto gene deste operon, pqsE, tem como produto a enzima pqsE, uma metalo-hidrolase que estimula a produção de elastase, piocianina e ramnolipídeo (Rampioni et al, 2010;Mukherjee et al, 2018;Soheili et al, 2019).…”

Section: Figura 1 -Estrutura Química Das Moléculas Autoindutoras Presunclassified

A influência do quórum sensing na formação do biofilme por Pseudomonas aeruginosa

Neves

Nunes²,

Rocha

et al. 2021

RSD

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As bactérias se organizam de forma agregada numa matriz extracelular, chamada biofilme, estrutura que confere proteção a bactéria a ação dos antimicrobianos e a resposta imune do hospedeiro. Assim, Pseudomonas aeruginosa, é classificado como um micro-organismo oportunista, responsável por causar altos números de infecções hospitalares devido a resistência bacteriana desenvolvida por fatores de virulência como o biofilme, controlados por o sistema quorum sensing. Desse modo, o objetivo desse trabalho foi descrever a comunicação das células bacteriana para formação do biofilme por P. aeruginosa, durante o processo de colonização e infecção no hospedeiro. Seguiu-se a metodologia de uma revisão narrativa, com base nos artigos publicados entre os anos de 2000 e 2020, indexados na Biblioteca Virtual em Saúde (BVS), utilizando para busca os descritores: “quorum sensing”, "Pseudomonas aeruginosa", "biofilm", "virulence factors", "Flagella", "pili", "bacterial adhesion" "polysaccharide" "adhesins" e "biofilm matrix”. Foram selecionados artigos publicados na íntegra, em inglês, entre os anos de 1990 e 2020. Foram excluídos artigos incompletos, duplicados e trabalhos acadêmicos como teses e dissertações. Evidenciou-se que a resistência bacteriana de P. aeruginosa aos antibióticos está relacionada a sua alta capacidade de adaptação a ambientes hostis e aos mecanismos de resistência desenvolvidos pela espécie, especialmente a formação do biofilme bacteriano pelo sistema quorum sensing a partir da biossíntese de moléculas autoindutoras como: N-3-oxo-dodecanoil homoserina lactona, N-butanoil-homoserina lactona e 2-heptil-3-hidroxi-4-quinolona, responsáveis por mediar a produção dos fatores de virulência. Esta revisão abordou os aspectos gerais que envolve a patogenicidade oriunda da comunicação bacteriana durante o seu processo de colonização.

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Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review

Cited by 59 publications

References 51 publications

Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa?

Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa?

SPRINT: a Cas13a-based platform for detection of small molecules

A influência do quórum sensing na formação do biofilme por Pseudomonas aeruginosa

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