Increased Innate Immune Susceptibility in Hyperpigmented Bacteriophage-Resistant Mutants of Pseudomonas aeruginosa

Menon, Nitasha D.; Penziner, Samuel; Montaño, Elizabeth T.; Zurich, Raymond H.; Pride, David T.; Nair, Bipin G.; Kumar, Geetha B.; Nizet, Victor

doi:10.1128/aac.00239-22

Cited by 15 publications

(12 citation statements)

References 40 publications

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“…The two genes that are always deleted among the brown phenotype mutants include hmgA , which is related to the brown pigment accumulation ( Rodríguez-Rojas et al, 2009 ; Hosseinidoust et al, 2013 ), and galU , which is involved in lipopolysaccharide production, bacterial virulence, and synthesis of a component by which the phage recognizes ( Le et al, 2015 ; Pires et al, 2017 ; Yang et al, 2020 ). Furthermore, the brown phenotype-producing P. aeruginosa strains that are resistant to phages AM.P2, Mat, and Kat have been recently shown to also exhibit hypersusceptibility toward human antimicrobial peptide LL-37 ( Menon et al, 2022 ). Even though the deletion of this particular genomic fragment has been well conserved among the phage-resistant P. aeruginosa strains, it is still elusive how the deletion of this genomic region would contribute to the antibiotic hypersensitivity of phage-resistant P. aeruginosa .…”

Section: Discussionmentioning

confidence: 99%

Phage-resistant Pseudomonas aeruginosa against a novel lytic phage JJ01 exhibits hypersensitivity to colistin and reduces biofilm production

et al. 2022

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Pseudomonas aeruginosa, a major cause of nosocomial infections, has been categorized by World Health Organization as a critical pathogen urgently in need of effective therapies. Bacteriophages or phages, which are viruses that specifically kill bacteria, have been considered as alternative agents for the treatment of bacterial infections. Here, we discovered a lytic phage targeting P. aeruginosa, designated as JJ01, which was classified as a member of the Myoviridae family due to the presence of an icosahedral capsid and a contractile tail under TEM. Phage JJ01 requires at least 10 min for 90% of its particles to be adsorbed to the host cells and has a latent period of 30 min inside the host cell for its replication. JJ01 has a relatively large burst size, which releases approximately 109 particles/cell at the end of its lytic life cycle. The phage can withstand a wide range of pH values (3–10) and temperatures (4–60°C). Genome analysis showed that JJ01 possesses a complete genome of 66,346 base pairs with 55.7% of GC content, phylogenetically belonging to the genus Pbunavirus. Genome annotation further revealed that the genome encodes 92 open reading frames (ORFs) with 38 functionally predictable genes, and it contains neither tRNA nor toxin genes, such as drug-resistant or lysogenic-associated genes. Phage JJ01 is highly effective in suppressing bacterial cell growth for 12 h and eradicating biofilms established by the bacteria. Even though JJ01-resistant bacteria have emerged, the ability of phage resistance comes with the expense of the bacterial fitness cost. Some resistant strains were found to produce less biofilm and grow slower than the wild-type strain. Among the resistant isolates, the resistant strain W10 which notably loses its physiological fitness becomes eight times more susceptible to colistin and has its cell membrane compromised, compared to the wild type. Altogether, our data revealed the potential of phage JJ01 as a candidate for phage therapy against P. aeruginosa and further supports that even though the use of phages would subsequently lead to the emergence of phage-resistant bacteria, an evolutionary trade-off would make them more sensitive to antibiotics.

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Section: Discussionmentioning

confidence: 99%

Phage-resistant Pseudomonas aeruginosa against a novel lytic phage JJ01 exhibits hypersensitivity to colistin and reduces biofilm production

et al. 2022

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“…Menon et al. explored the properties of hyperpigmented P. aeruginosa mutants, which developed resistance to applied phages [ 32 ]. To address this, the authors administered the phages AM.P2, Mat, and Kat to P. aeruginosa PA01 resulting in resistant mutants designated P. aeruginosa AM.P2-X-1, Mat-X-1, and Kat-X-2.…”

Section: Resultsmentioning

confidence: 99%

“…The killing of the pyomelanogenic mutants in whole blood or serum turned out to be notably faster compared to the phage-sensitive PA01. Furthermore, the P. aeruginosa AM.P2-X-1 mutant strain survived within the lung of infected mice with 10-times lower counts if compared to P. aeruginosa [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, developing resistance to phages rendered MDR P. aeruginosa more sensitive to antibiotics again in several studies [ 15 , 18 , 32 ]. Basically, the respective sensitivity to phages and antibiotics is variable and reciprocally correlated [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…In consequence, phage therapy was discouraged in patients with neutropenia [ 30 ], even though, therapeutic success was achieved in neutropenic mice [ 13 , 15 , 18 ]. Interestingly, resistance to phages was accompanied by facilitated elimination through cathelicidin LL-37, underscoring distinct synergistic effects [ 32 ] as visualized by Figure. 5 .…”

Section: Discussionmentioning

confidence: 99%

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Phage therapy in lung infections caused by multidrug-resistant Pseudomonas aeruginosa – A literature review

Eiselt,

Bereswill,

Heimesaat

2024

EuJMI

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Pulmonary infections of patients with cystic fibrosis (CF) or in intensive care units are frequently caused by the Gram-negative opportunistic pathogen Pseudomonas aeruginosa. Since these bacteria are commonly inherently multidrug-resistant (MDR) and hence, antibiotic treatment options are limited, bacteriophages may provide alternative therapeutic and prophylactic measures in the combat of pneumonia caused by P. aeruginosa. This prompted us to perform a comprehensive literature survey of current knowledge regarding effects of phages applied against pulmonary P. aeruginosa infections. The included 23 studies revealed that P. aeruginosa specific phages lyse and eliminate the bacteria even in case of biofilm production in vitro, whereas application to mice and men resulted in mitigated P. aeruginosa induced clinical signs and enhanced survival. Besides distinct host immune responses, no major adverse effects limiting therapeutic and/or prophylactic phage application were noted. However, the immune system and antibiotics generate synergies with phages due to the mutable sensitivity of P. aeruginosa. In conclusion, results summarized in this review provide evidence that phages constitute promising alternative treatment options for lung infections caused by MDR P. aeruginosa. Further studies are needed, however, to underscore the efficacy and safety aspects of phages application to infected patients including immune-compromised individuals.

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Genomic insights into drug resistance and virulence determinants in rare pyomelanin-producing clinical isolates of Acinetobacter baumannii

Panda,

GK,

Sawant

et al. 2024

Eur J Clin Microbiol Infect Dis

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Increased Innate Immune Susceptibility in Hyperpigmented Bacteriophage-Resistant Mutants of Pseudomonas aeruginosa

Cited by 15 publications

References 40 publications

Phage-resistant Pseudomonas aeruginosa against a novel lytic phage JJ01 exhibits hypersensitivity to colistin and reduces biofilm production

Phage-resistant Pseudomonas aeruginosa against a novel lytic phage JJ01 exhibits hypersensitivity to colistin and reduces biofilm production

Phage therapy in lung infections caused by multidrug-resistant Pseudomonas aeruginosa – A literature review

Genomic insights into drug resistance and virulence determinants in rare pyomelanin-producing clinical isolates of Acinetobacter baumannii

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