Design, synthesis, and biological evaluation of 3-amino-2-oxazolidinone derivatives as potent quorum-sensing inhibitors of Pseudomonas aeruginosa PAO1

Jiang, Kai; Yan, Xinmin; Yu, Jiahao; Xiao, Zijian; Wu, Hao; Zhao, Meihua; Yue, Yuandong; Zhou, Xiaoping; Xiao, Junhai; Lin, Feng

doi:10.1016/j.ejmech.2020.112252

Cited by 39 publications

(28 citation statements)

References 53 publications

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“…Motility and antibiotic resistance have been linked in a variety of pathogens such as Campylobacter jejuni, in which enhanced motility is associated with increased resistance to polymyxin B and ciprofloxacin [28]. In P. aeruginosa, quorum sensing inhibition has been shown to inhibit motility, biofilm formation, and resistance to meropenem [29]. Thus, it is plausible to hypothesize that these phenotypes are governed by similar overlapping regulatory networks in A. baumannii.…”

Section: Discussionmentioning

confidence: 99%

Analysis of virulence phenotypes and antibiotic resistance in clinical strains of Acinetobacter baumannii isolated in Nashville, Tennessee

et al. 2021

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Background Acinetobacter baumannii is a gram-negative bacterium which causes opportunistic infections in immunocompromised hosts. Genome plasticity has given rise to a wide range of strain variation with respect to antimicrobial resistance profiles and expression of virulence factors which lead to altered phenotypes associated with pathogenesis. The purpose of this study was to analyze clinical strains of A. baumannii for phenotypic variation that might correlate with virulence phenotypes, antimicrobial resistance patterns, or strain isolation source. We hypothesized that individual strain virulence phenotypes might be associated with anatomical site of isolation or alterations in susceptibility to antimicrobial interventions. Methodology A cohort of 17 clinical isolates of A. baumannii isolated from diverse anatomical sites were evaluated to ascertain phenotypic patterns including biofilm formation, hemolysis, motility, and antimicrobial resistance. Antibiotic susceptibility/resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin was determined. Results Antibiotic resistance was prevalent in many strains including resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin. All strains tested induced hemolysis on agar plate detection assays. Wound-isolated strains of A. baumannii exhibited higher motility than strains isolated from blood, urine or Foley catheter, or sputum/bronchial wash. A. baumannii strains isolated from patient blood samples formed significantly more biofilm than isolates from wounds, sputum or bronchial wash samples. An inverse relationship between motility and biofilm formation was observed in the cohort of 17 clinical isolates of A. baumannii tested in this study. Motility was also inversely correlated with induction of hemolysis. An inverse correlation was observed between hemolysis and resistance to ticarcillin-k clavulanate, meropenem, and piperacillin. An inverse correlation was also observed between motility and resistance to ampicillin-sulbactam, ceftriaxone, ceftoxamine, ceftazidime, ciprofloxacin, or levofloxacin. Conclusions Strain dependent variations in biofilm and motility are associated with anatomical site of isolation. Biofilm and hemolysis production both have an inverse association with motility in the cohort of strains utilized in this study, and motility and hemolysis were inversely correlated with resistance to numerous antibiotics.

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Section: Discussionmentioning

confidence: 99%

Analysis of virulence phenotypes and antibiotic resistance in clinical strains of Acinetobacter baumannii isolated in Nashville, Tennessee

et al. 2021

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“…The most active derivative 15 exhibited interesting anti-virulence properties against a P. aeruginosa PAO1 strain at 162.5 µM, with 40, 22, 16 and 57% of inhibition of biofilm, pyocyanin, elastase and rhamnolipid production, respectively (Scheme 5, Table 1). This compound prolonged the lifespan of PAO1-infected nematodes in combination with meropenem, enhancing the sensibility of biofilm bacteria to the ATB [91].…”

Section: Ahl Autoinducer Analog Qsismentioning

confidence: 99%

Quorum Sensing Inhibitors to Quench P. aeruginosa Pathogenicity

2021

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The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues. Furthermore, P. aeruginosa has the capacity to establish biofilms that reinforce its virulence and intrinsic drug resistance. The regulation of biofilm and virulence factor production of this micro-organism is controlled by a specific bacterial communication system named Quorum Sensing (QS). The development of anti-virulence agents targeting QS that could attenuate P. aeruginosa pathogenicity without affecting its growth seems to be a promising new therapeutic strategy. This could prevent the selective pressure put on bacteria by the conventional antibiotics that cause their death and promote resistant strain survival. This review describes the QS-controlled pathogenicity of P. aeruginosa and its different specific QS molecular pathways, as well as the recent advances in the development of innovative QS-quenching anti-virulence agents to fight anti-bioresistance.

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“…During the growth period, under infection conditions, the resistance of bacteria to antibiotics increases 10 to 1000 times. 37,118 Current biolm targeting methods can be divided into two categories: the rst is a physical-mechanical method designed to interrupt and eliminate the biolm, and the second method involves the use of antibiotics or antibiotics in the matrix to prevent the formation of biolm. 120 DR-1018 (or just 1018) is a small cationic synthetic peptide (VRLIVAVRIWRR-NH 2 ) that has been developed based on bactenecin, a peptide antibiotic isolated from bovine neutrophil granules.…”

Section: Targeting Biolmsmentioning

confidence: 99%

“…In vivo , compound 29 significantly prolonged the lifespan of wild-type C. elegans N2 infected by Pseudomonas aeruginosa PAO1. In summary, compound 29 can be considered as a drug candidate for drug-resistant Pseudomonas aeruginosa PAO1, providing a tool for finding new antibacterial drug 118 ( Fig. 19 ).…”

Section: Targeting Virulence Factormentioning

confidence: 99%

Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance

et al. 2021

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Design, synthesis, and biological evaluation of 3-amino-2-oxazolidinone derivatives as potent quorum-sensing inhibitors of Pseudomonas aeruginosa PAO1

Cited by 39 publications

References 53 publications

Analysis of virulence phenotypes and antibiotic resistance in clinical strains of Acinetobacter baumannii isolated in Nashville, Tennessee

Analysis of virulence phenotypes and antibiotic resistance in clinical strains of Acinetobacter baumannii isolated in Nashville, Tennessee

Quorum Sensing Inhibitors to Quench P. aeruginosa Pathogenicity

Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance

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