Acidic Microenvironment Determines Antibiotic Susceptibility and Biofilm Formation of Pseudomonas aeruginosa

Lin, Qiao; Pilewski, Joseph M.; Di, Y. Peter

doi:10.3389/fmicb.2021.747834

Cited by 29 publications

(16 citation statements)

References 83 publications

(90 reference statements)

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“…The acidic environment stimulated increased P. aeruginosa biofilm formation, promoted faster bacterial evolution to improve antibiotic resistance, and increased the expression of multiple biofilm/ virulence-related genes. Therefore, the use of simple pH-buffering agents alongside antibiotics may be a novel treatment strategy for combating chronic infection in the acidic, DNA-enriched lungs of clinic patients (Lin et al, 2021).…”

Section: Dnasementioning

confidence: 99%

Treatment of Pseudomonas aeruginosa infectious biofilms: Challenges and strategies

et al. 2022

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Pseudomonas aeruginosa, a Gram-negative bacterium, is one of the major pathogens implicated in human opportunistic infection and a common cause of clinically persistent infections such as cystic fibrosis, urinary tract infections, and burn infections. The main reason for the persistence of P. aeruginosa infections is due to the ability of P. aeruginosa to secrete extracellular polymeric substances such as exopolysaccharides, matrix proteins, and extracellular DNA during invasion. These substances adhere to and wrap around bacterial cells to form a biofilm. Biofilm formation leads to multiple antibiotic resistance in P. aeruginosa, posing a significant challenge to conventional single antibiotic therapeutic approaches. It has therefore become particularly important to develop anti-biofilm drugs. In recent years, a number of new alternative drugs have been developed to treat P. aeruginosa infectious biofilms, including antimicrobial peptides, quorum-sensing inhibitors, bacteriophage therapy, and antimicrobial photodynamic therapy. This article briefly introduces the process and regulation of P. aeruginosa biofilm formation and reviews several developed anti-biofilm treatment technologies to provide new directions for the treatment of P. aeruginosa biofilm infection.

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Section: Dnasementioning

confidence: 99%

Treatment of Pseudomonas aeruginosa infectious biofilms: Challenges and strategies

et al. 2022

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“…For planktonic populations, 1/100 or approximately 2.5 × 10 6 colony forming units (CFU)/mL of total overnight culture was transferred into fresh M9 media supplemented with colistin. For biofilm populations, a bead transfer-based biofilm evolution system was used according to a method described previously [ 21 , 22 , 23 ]. Briefly, a single colonized 7 mm polystyrene bead, approximately 2.5 × 10 5 CFU/mL, was transferred into M9 medium supplemented with colistin and two sterile polystyrene beads.…”

Section: Methodsmentioning

confidence: 99%

Determination of Mutational Timing of Colistin-Resistance Genes through Klebsiella pneumoniae Evolution

Kuhn

2023

Pharmaceutics

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The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (KP), one of the carbapenem-resistant Enterobacteriaceae (CRE), is now an emerging cause of antibiotic-resistant nosocomial infections associated with high rates of morbidity and mortality. Colistin, or polymyxin E, is a last-resort peptide antibiotic used to treat multidrug-resistant (MDR) Gram-negative bacterial infections including KP. Unfortunately, resistance to colistin is rising with increasing use in the clinical setting. Although clinical evidence links certain mutations to colistin resistance (COL-R) in KP, the origination and association of the mutations remain unclear. We hypothesize that the timing of COL-R mutations influences the development and progression of KP resistance to colistin. We performed planktonic and biofilm in vitro experimental evolutions of KP strain ATCC 43816 under increasing colistin concentrations to characterize the temporal regulation of critical COL-R mutations throughout COL-R progression. The resistance generation and mutation profiles of independently evolved bacterial populations with different lifestyles were compared. Genes with various functions theorize the timeline in which key mutations are generated and their roles in the progression of COL-R. Our results aim to advance the research and development of effective therapeutics to treat MDR bacterial infection as the dissemination of CRE continues to be a severe public health threat.

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“…Using MOE-2019 software (CCG ® ; Montreal; Canada), the two QS targets ( P. aeruginosa QscR PDB; 3SZT) and C. violaceum CviR PDB; 3QP5) were prepared through three-dimensional protonation, atom types and connectivity auto-correction, and partial charge assignment at physiological neutral pH 7.4 [ 86 , 87 ]. The investigated α -adrenoreceptor inhibitors, as well as control antagonists, were built via MOE module using respective SMILES line annotations.…”

Section: Methodsmentioning

confidence: 99%

Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria

et al. 2022

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Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, α-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the α-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven α-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked α-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against Chromobacterium violaceum and Pseudomonas aeruginosa. Terazosin showed a significant ability to diminish the QS-controlled pigment production in C. violaceum. Moreover, Terazosin decreased the P. aeruginosa biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the P. aeruginosa pathogenesis. In conclusion, α-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage.

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Acidic Microenvironment Determines Antibiotic Susceptibility and Biofilm Formation of Pseudomonas aeruginosa

Cited by 29 publications

References 83 publications

Treatment of Pseudomonas aeruginosa infectious biofilms: Challenges and strategies

Treatment of Pseudomonas aeruginosa infectious biofilms: Challenges and strategies

Determination of Mutational Timing of Colistin-Resistance Genes through Klebsiella pneumoniae Evolution

Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria

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