Using Bacteriophages as a Trojan Horse to the Killing of Dual-Species Biofilm Formed by Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus

Tkhilaishvili, Tamta; Wang, Lei; Perka, Carsten; Trampuž, Andrej; Moreno, Mercedes Gonzalez

doi:10.3389/fmicb.2020.00695

Cited by 41 publications

(36 citation statements)

References 46 publications

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“…Recently, a number of papers have been published that examine different aspects of PAS on P. aeruginosa biofilms [ 16 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. We were particularly interested to discover whether pragmatic PAS with a lytic phage and AzLys was more effective at eradicating PA01 biofilms than phage treatment alone.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, re-colonization is common due to P. aeruginosa persistence in the upper airways [ 66 ]. However, PAS has the potential to improve treatment for chronic infections with the combined action of antibiotics and select phages increasing killing activity against pathogens [ 13 , 14 , 16 , 36 , 37 , 41 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ], and a variety of studies have shown that the combined use of antibiotics and phages reduces the emergence of resistance to one or both killing agents [ 16 , 68 , 69 , 70 , 74 , 75 , 76 , 77 ]. In this study, we show that AzLys is able to increase the activity of phages E79 and phiKZ.…”

Section: Discussionmentioning

confidence: 99%

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Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01

2021

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Pseudomonas aeruginosa is a pernicious bacterial pathogen that is difficult to treat because of high levels of antibiotic resistance. A promising alternative treatment option for such bacteria is the application of bacteriophages; the correct combination of phages plus antibiotics can produce synergistic inhibitory effects. In this study, we describe morphological changes induced by sub-MIC levels of the antibiotic aztreonam lysine (AzLys) on P. aeruginosa PA01, which may in part explain the observed phage–antibiotic synergy (PAS). One-step growth curves for phage E79 showed increased adsorption rates, decreased infection latency, accelerated time to lysis and a minor reduction in burst size. Phage E79 plus AzLys PAS was also able to significantly reduce P. aeruginosa biofilm growth over 3-fold as compared to phage treatment alone. Sub-inhibitory AzLys-induced filamentation of P. aeruginosa cells resulted in loss of twitching motility and a reduction in swimming motility, likely due to a reduction in the number of polar Type IV pili and flagella, respectively, on the filamented cell surfaces. Phage phiKZ, which uses Type IV pili as a receptor, did not exhibit increased activity with AzLys at lower sub-inhibitory levels, but still produced phage–antibiotic synergistic killing with sub-inhibitory AzLys. A one-step growth curve indicates that phiKZ in the presence of AzLys also exhibits a decreased infection latency and moderately undergoes accelerated time to lysis. In contrast to prior PAS studies demonstrating that phages undergo delayed time to lysis with cell filamentation, these PAS results show that phages undergo accelerated time to lysis, which therefore suggests that PAS is dependent upon multiple factors, including the type of phages and antibiotics used, and the bacterial host being tested.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01

2021

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“…Such confirmation, involving clinical trials, is still to be determined and might bring new insights into the potential application of such a treatment. We need to remember that P. aeruginosa and S. aureus are pathogens that tend to create mixed biofilm, significantly more resistant to known antimicrobials (Tkhilaishvili et al, 2020). This phenomenon involves the necessity to use higher antibiotic doses, too high to be reached in clinical practice (Tkhilaishvili et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Anti-biofilm activity of bacteriophages and lysins in chronic rhinosinusitis

Łusiak-Szelachowska¹,

Weber‐Dąbrowska²,

Żaczek³

et al. 2021

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337-1172. M. Łusiak-Szelachowska and B. Weber-Dąbrowska are equal first authors. Abbreviations: AB Alamar Blue assay; AECRS exacerbation of chronic rhinosinusitis; ATCC American Type Culture Collection; CF cystic fibrosis; CFU colony forming unit, Cls clinical strains; CRS chronic rhinosinusitis; CSF cerebrospinal fluid; EDTA ethylenediaminetetraacetic acid; ESS endoscopic sinus surgery; ISMN isosorbide mononitrate; LFNO liposomal formulated nitric oxide; LPS lipopolysaccharide; MBEC minimum biofilm eradication concentration assay; MDR antibiotic resistant variants; MDT antibiotic tolerant variants; MIC minimum inhibitory concentration; MOI phage multiplicity of infection; MRSA methicillin resistant S. aureus; MSSA methicillin sensitive S. aureus; NEC nasal epithelial cells; NO nitric oxide; NOS nitric oxide synthase; PFU plaque forming unit; RBP receptor binding proteins; SDT single-drug tolerance

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“…153 Initial studies in humans have shown promising results of phage therapy as an alternative for treating infections due to highly resistant bacteria. [154][155][156] Bacteriocins are proteins secreted by bacteria for colonization of the host by eliminating other bacterial competitor strains that share the same environment. 157 Bacteriocins are produced mainly by GNB such as P. aeruginosa and E. coli.…”

Section: New Antibiotic Agentsmentioning

confidence: 99%

Emerging Resistance of Gram Negative Pathogens in Community-Acquired Pneumonia

Amati

Restrepo²

2020

Semin Respir Crit Care Med

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AbstractIn recent decades, there has been a growing interest about the role of gram negative bacteria in community-acquired pneumonia (CAP), especially Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. The prevalence of these pathogens differs largely according to the local ecology and the geographical location. Identifying gram negative bacteria, and in particular resistant gram negative bacteria, is of paramount importance in patients with CAP because these pathogens are associated with higher clinical severity and unfavorable outcomes. The use of individualized risk factors to predict each pathogen is a helpful strategy that needs to be locally validated. However, it should be taken into account that most of the risk factors identified in the literature are heterogeneously defined or lack consistency. New diagnostic techniques, such as molecular testing, are promising methods for early detection of these gram negative pathogens. The increasing mechanisms of resistance to antibiotics of these pathogens have limited our therapeutic approach. This narrative review focuses on the epidemiology, risk factors, diagnosis, and therapeutic options for the most relevant gram negative bacteria that cause CAP.

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Using Bacteriophages as a Trojan Horse to the Killing of Dual-Species Biofilm Formed by Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus

Cited by 41 publications

References 46 publications

Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01

Aztreonam Lysine Increases the Activity of Phages E79 and phiKZ against Pseudomonas aeruginosa PA01

Anti-biofilm activity of bacteriophages and lysins in chronic rhinosinusitis

Emerging Resistance of Gram Negative Pathogens in Community-Acquired Pneumonia

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