Pseudomonas aeruginosa Biofilms

Thi, Minh Tam Tran; Wibowo, David; Rehm, Bernd H. A.

doi:10.3390/ijms21228671

Cited by 495 publications

(402 citation statements)

References 221 publications

(167 reference statements)

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“…In addition, exopolysaccharides, such as Psl, Pel, and extracellular DNA, are abundant components of the biofilm in P. aeruginosa [ 45 , 46 ]. These components adhere to each other and play an essential role in the highly complex biofilm formation, which is beneficial for growth and antibiotic tolerance [ 47 , 48 , 49 ]. P. aeruginosa expresses the soluble lectins lecA and lecB, both surface proteins capable of binding the exopolysaccharides [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Hofmann

Hirsch

Ruthstein

2021

IJMS

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Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.

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Section: Introductionmentioning

confidence: 99%

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Hofmann

Hirsch

Ruthstein

2021

IJMS

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“…In 2005, Banin et al conducted a study in which they described biofilm formation in terms of four important steps: (I) attachment, (II) microcolony formation, (III) maturation of biofilm, and (IV) dispersal, whereas a review article published by Thi et al in 2020 split the first step into (attachment) initial reversible adhesion and irreversible attachment, thereby making it five steps in biofilm formation [ 24 , 9 ]. Figure 4 is a pictorial representation of the same.…”

Section: Reviewmentioning

confidence: 99%

“…Biofilm formation is a coordinated effort by individual cells to adapt to cell density changes and environmental stress through an interconnected signaling pathway called quorum sensing (QS). There are four clear pathways in the QS circuits of P. aeruginosa , namely Las, Rhl, PQS, and IQS, of which PQS is triggered by variation in iron concentration [ 9 ]. In their study, Yang et al presented evidence that during low iron concentration, biofilm development occurs via stimulation of the PQS genes and the formation of extracellular DNA.…”

Section: Reviewmentioning

confidence: 99%

“…It involves biofilm formation, a structured aggregate of bacteria implanted in a self-produced matrix consisting of polysaccharide, protein, and DNA [ 7 ]. Biofilms help to endure unpredictable changes in temperature fluctuation and nutrient availability and also serve as a diffusion-barrier to limit antibiotic access to the bacterial cells [ 8 - 9 ]. Figure 1 below illustrates the distinctive time course of P. aeruginosa colonization of the cystic fibrosis respiratory tract and resistance mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Can Targeting Iron Help in Combating Chronic Pseudomonas Infection? A Systematic Review

Firoz¹,

Haris²,

Hussain³

et al. 2021

Cureus

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Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by Pseudomonas aeruginosa (P. aeruginosa). Eradication of these infections has become a challenge as P. aeruginosa has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation, which is the predominant resistance mechanism used by P. aeruginosa to combat antibiotics. The increased iron content in cystic fibrosis patients' sputum samples explains their increased susceptibility to Pseudomonas infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic Pseudomonas infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic Pseudomonas infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.

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“…It is known to form drug-immune biofilms and to cause urinary tract infections; ear, nose, and throat infections; and cardiovascular and bloodstream infections. It devastates immune-compromised individuals such as those suffering from cystic fibrosis, cancer, burns, and major surgery [ 17 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Anti-Virulence Therapeutics against Mono-ADP-Ribosyltransferase Toxins

Lugo

Merrill

2020

Toxins

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Mono-ADP-ribosyltransferase toxins are often key virulence factors produced by pathogenic bacteria as tools to compromise the target host cell. These toxins are enzymes that use host cellular NAD+ as the substrate to modify a critical macromolecule target in the host cell machinery. This post-translational modification of the target macromolecule (usually protein or DNA) acts like a switch to turn the target activity on or off resulting in impairment of a critical process or pathway in the host. One approach to stymie bacterial pathogens is to curtail the toxic action of these factors by designing small molecules that bind tightly to the enzyme active site and prevent catalytic function. The inactivation of these toxins/enzymes is targeted for the site of action within the host cell and small molecule therapeutics can function as anti-virulence agents by disarming the pathogen. This represents an alternative strategy to antibiotic therapy with the potential as a paradigm shift that may circumvent multi-drug resistance in the offending microbe. In this review, work that has been accomplished during the past two decades on this approach to develop anti-virulence compounds against mono-ADP-ribosyltransferase toxins will be discussed.

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Pseudomonas aeruginosa Biofilms

Cited by 495 publications

References 221 publications

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Can Targeting Iron Help in Combating Chronic Pseudomonas Infection? A Systematic Review

Development of Anti-Virulence Therapeutics against Mono-ADP-Ribosyltransferase Toxins

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