Current knowledge in the use of bacteriophages to combat infections caused by Pseudomonas aeruginosa in cystic fibrosis

Martínez-Gallardo, María José; Villicaña, Claudia; Yocupicio-Monroy, Martha; Alcaráz-Estrada, Sofía Lizeth; León‐Félix, Josefina

doi:10.1007/s12223-022-00990-5

Cited by 12 publications

(15 citation statements)

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“…Research for new antimicrobials is a priority given the limitations in the currently available antibiotic treatments for PwCF, particularly in the setting of an aging patient population and high prevalence of MDR pathogens. Phage therapy utilizes viruses to infect specific bacteria and replicate the viral genome in the bacteria, ultimately lysing the host bacteria and killing it [ 37 , 70 ]. Phages, also known as bacteriophages, have been studied for decades, but they recently gained momentum in the CF research community because they may serve as an alternative treatment option with potentially fewer side effects for complex bacterial infections in PwCF [ 71 ].…”

Section: Antimicrobial Therapiesmentioning

confidence: 99%

“…Phages, also known as bacteriophages, have been studied for decades, but they recently gained momentum in the CF research community because they may serve as an alternative treatment option with potentially fewer side effects for complex bacterial infections in PwCF [ 71 ]. Phages occur naturally in the environment, and they are found mostly in wastewater, reserves, lakes, and mammalian serum or compost [ 70 , 71 ]. They are currently being investigated for a variety of pathogenic infections in humans, including, but not limited, to sepsis, urinary tract, respiratory, skin, and joint infections [ 42 ].…”

Section: Antimicrobial Therapiesmentioning

confidence: 99%

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Advances in the Cystic Fibrosis Drug Development Pipeline

Esposito,

Kamper,

Trentacoste

et al. 2023

Life

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Cystic fibrosis is a genetic disease that results in progressive multi-organ manifestations with predominance in the respiratory and gastrointestinal systems. The significant morbidity and mortality seen in the CF population has been the driving force urging the CF research community to further advance treatments to slow disease progression and, in turn, prolong life expectancy. Enormous strides in medical advancements have translated to improvement in quality of life, symptom burden, and survival; however, there is still no cure. This review discusses the most current mainstay treatments and anticipated therapeutics in the CF drug development pipeline within the mechanisms of mucociliary clearance, anti-inflammatory and anti-infective therapies, restoration of the cystic fibrosis transmembrane conductance regulator (CFTR) protein (also known as highly effective modulator therapy (HEMT)), and genetic therapies. Ribonucleic acid (RNA) therapy, gene transfer, and gene editing are being explored in the hopes of developing a treatment and potential cure for people with CF, particularly for those not responsive to HEMT.

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Section: Antimicrobial Therapiesmentioning

confidence: 99%

Section: Antimicrobial Therapiesmentioning

confidence: 99%

Advances in the Cystic Fibrosis Drug Development Pipeline

Esposito,

Kamper,

Trentacoste

et al. 2023

Life

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“…In addition to intrinsic resistance to various antimicrobial agents (β-lactam and penem group of antibiotics), P. aeruginosa can acquire resistance to other antibiotics using the mechanisms depicted in Figure-1 [16]. Although several antibiotics continue to work well against P. aeruginosa, more and more researchers recommend alternative solutions that can counteract antibiotic resistance in P. aeruginosa, effectively fight sensitive strains, and reduce the risks of acquiring antibiotic resistance [17][18][19][20][21]. Recent studies [19][20][21] have suggested that nanoparticles (NPs) and nanocomplexes constitute a suitable alternative for combating microorganisms in general and Pseudomonas, in particular, by limiting the possibility for these strains to develop resistance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of green-engineered silver nanoparticles using Cymbopogon citratus (lemongrass) and its antibacterial activity against clinical Pseudomonas aeruginosa

Arsene,

Davares,

Goriainov

et al. 2024

Int J One Health

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Background and Aim: The use of bioengineered nanocomposites as antimicrobials has increased in recent years, but very few investigations have been conducted to test their effectiveness against Pseudomonas aeruginosa, a pathogen presenting public health risks that can impact both humans and animals. The aim of this study was to assess the antimicrobial potential of phytofabricated silver nanoparticles synthesized using lemongrass extract against clinical isolates of P. aeruginosa. Materials and Methods: The extraction of active compounds from the leaves of Cymbopogon citratus was performed using ethanol (80%) as a solvent, high-performance liquid chromatography-mass spectrometry was used to analyze the chemical composition of the extract, the synthesis of silver nanoparticles (AgNPs) was done using silver nitrate (AgNO3) as a precursor, and the antimicrobial and antibiofilm activity of the extract and the AgNPs phytofabricated was assessed against 10 clinical strains of P. aeruginosa. Results: Lemongrass extract was found to consist of the following main compounds: Caffeic acid (445.21 ± 32.77 μg/g), p-coumaric acid (393.32 ± 39.56 μg/g), chlorogenic acid (377.65 ± 4.26 μg/g), quinic acid (161.52 ± 17.62 μg/g), and quercetin-3-glucoside (151.35 ± 11.34 μg/g). AgNPs were successfully phytofabricated using 2.5 mM AgNO3. The ultraviolet (UV)-visible absorption spectra of the AgNPs showed a localized surface plasmon resonance at 464 nm with an absorbance of 0.32 A. The 50x hydrodynamic diameter was 50.29 nm with a surface area value of 120.10 m2/ cm3, and the volume mean diameter and Sauter mean diameter were 50.63 nm and 49.96 nm, respectively. Despite the compound found in lemongrass extract, no antimicrobial activity was observed with the extract, while AgNPs exhibited noteworthy dose-dependent antimicrobial activity with inhibition diameters up to 24 mm and minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 2 to 16 and 4–64 µg/mL, respectively. AgNPs also demonstrated significant antibiofilm activity by inhibiting biofilms up to 99% between MIC/2 and 2MIC. Conclusion: The present study suggests that lemongrass is a good candidate for the synthesis of AgNPs with good physicochemical characteristics and having a strong anti-pseudomonas activity. Further research is needed to assess the stability and safety of these AgNPs. Keywords: antibiofilm capacity, antimicrobial activity, green synthesis, lemongrass, Pseudomonas aeruginosa, silver nanoparticles.

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“…Pseudomonas aeruginosa (PA) is a Gram-negative bacterium responsible for 51,000 infections with 2,700 deaths in the US every year ( 1 ) and approximately 559,000 deaths globally in 2019 ( 2 ). PA is also a common complication of cystic fibrosis (CF), with 80% of CF patients developing PA infection ( 3 ) and causing chronic infection in 41% of un-transplanted adults with CF ( 4 ). Antimicrobial resistance of PA infections has become an increased concern ( 1 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

A synthetic biology approach to assemble and reboot clinically relevant Pseudomonas aeruginosa tailed phages

Ipoutcha,

Racharaks,

Huttelmaier

et al. 2024

Microbiol Spectr

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The rise in the frequency of antibiotic resistance has made bacterial infections, specifically Pseudomonas aeruginosa , a cause for greater concern. Phage therapy is a promising solution that uses naturally isolated phages to treat bacterial infections. Ecological limitations, which stipulate a discrete host range and the inevitable evolution of resistance, may be overcome through a better understanding of phage biology and the utilization of engineered phages. In this study, we developed a synthetic biology approach to construct tailed phages that naturally target clinically relevant strains of Pseudomonas aeruginosa . As proof of concept, we successfully cloned and assembled the JG024 and DMS3 phage genomes in yeast using transformation-associated recombination cloning and rebooted these two phage genomes in two different strains of P. aeruginosa . We identified factors that affected phage reboot efficiency like the phage species or the presence of antiviral defense systems in the bacterial strain. We have successfully extended this method to two other phage species and observed that the method enables the reboot of phages that are naturally unable to infect the strain used for reboot. This research represents a critical step toward the construction of clinically relevant, engineered P. aeruginosa phages. IMPORTANCE Pseudomonas aeruginosa is a bacterium responsible for severe infections and a common major complication in cystic fibrosis. The use of antibiotics to treat bacterial infections has become increasingly difficult as antibiotic resistance has become more prevalent. Phage therapy is an alternative solution that is already being used in some European countries, but its use is limited by the narrow host range due to the phage receptor specificity, the presence of antiviral defense systems in the bacterial strain, and the possible emergence of phage resistance. In this study, we demonstrate the use of a synthetic biology approach to construct and reboot clinically relevant P. aeruginosa tailed phages. This method enables a significant expansion of possibilities through the construction of engineered phages for therapy applications.

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Current knowledge in the use of bacteriophages to combat infections caused by Pseudomonas aeruginosa in cystic fibrosis

Cited by 12 publications

References 100 publications

Advances in the Cystic Fibrosis Drug Development Pipeline

Advances in the Cystic Fibrosis Drug Development Pipeline

Synthesis of green-engineered silver nanoparticles using Cymbopogon citratus (lemongrass) and its antibacterial activity against clinical Pseudomonas aeruginosa

A synthetic biology approach to assemble and reboot clinically relevant Pseudomonas aeruginosa tailed phages

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