@mastersthesis{MTMT:34110556,
	title = {Phage infection reinstates antibiotic sensitivity in MDR Pseudomonas aeruginosa: A study on phage and bacterial evolution},
	url = {https://m2.mtmt.hu/api/publication/34110556},
	author = {Koderi Valappil, Sarshad},
	doi = {10.14232/phd.11330},
	publisher = {Universití of Szeged},
	unique-id = {34110556},
	abstract = {The emergence of antibiotic resistance among bacterial pathogens is a significant public health threat affecting humans worldwide. In Europe, Pseudomonas aeruginosa contributes to almost 9% of overall multi-drug-resistant (MDR) infections. Alternative methods for controlling MDR pathogens have been explored for several decades. Bacteriophage therapy is one of the oldest and most efficient alternative solutions. The study described in this thesis began with the isolation and characterization of 25 MDR P. aeruginosa clinical strains and eigth novel lytic phages. The investigation disclosed the infection with two phage isolates, PIAS and PAPSZ1, led to the sequential appearance of phage-resistant colonies with two phenotypes (green and brown). We examined the evolutionary basis for the two types of mutants and uncovered phage mutants capable of infecting green mutants. Simultaneously we also learned that PIAS phage infected the host via the OrpM-MexXY system involved in drug efflux. Thus, the PIAS-resistant mutants decreased the minimum inhibitory concentrations (MIC) for several non-effective antibiotics. After this new insight into the evolutionary arms race between hosts and phages, we decided to use this window to comprehensively eradicate mutants by treating MDR strain with previously resistant antibiotics combined with PIAS phage. The in vitro study with PIAS phage-antibiotic combination completely prevented the formation and growth of mutants. We tested the same strategy in an in vivo rescue experiment in the mouse lung infection model, when combined with PIAS phage and fosfomycin. The combination therapy saved 75% of the animals. Later, we used PAPSZ1 phage to investigate whether phage mutants can suppress bacterial resistance. We isolated multiple PAPSZ1 mutants after a continuous infection cycle, which can block or suppress bacterial resistance and mutant formation and broaden the host specificity of the phages. Phages like PIAS and PAPSZ1 offer a unique window that can exploit to eradicate MDR bacteria. This study highlights the importance of preliminary and detailed examinations of phage-host bacterium interactions preceding the application of a given phage. The experimental data in this thesis shows that studying phage-host bacterium interactions and coevolution will help to utilize phage therapy’s full potential when treating MDR infections.},
	year = {2022}
}

@article{MTMT:32548543,
	title = {Survival Comes at a Cost: A Coevolution of Phage and Its Host Leads to Phage Resistance and Antibiotic Sensitivity of Pseudomonas aeruginosa Multidrug Resistant Strains},
	url = {https://m2.mtmt.hu/api/publication/32548543},
	author = {Koderi Valappil, Sarshad and Shetty, Prateek and Deim, Zoltán and Terhes, Gabriella and Zsoldiné Urbán, Edit and Váczi, Sándor and Patai, Roland and Polgár, Tamás Ferenc and Pertics, Botond Zsombor and Schneider, György and Kovács, Tamás and Rákhely, Gábor},
	doi = {10.3389/fmicb.2021.783722},
	journal-iso = {FRONT MICROBIOL},
	journal = {FRONTIERS IN MICROBIOLOGY},
	volume = {12},
	unique-id = {32548543},
	issn = {1664-302X},
	abstract = {The increasing ineffectiveness of traditional antibiotics and the rise of multidrug resistant (MDR) bacteria have necessitated the revival of bacteriophage (phage) therapy. However, bacteria might also evolve resistance against phages. Phages and their bacterial hosts coexist in nature, resulting in a continuous coevolutionary competition for survival. We have isolated several clinical strains of Pseudomonas aeruginosa and phages that infect them. Among these, the PIAS (Phage Induced Antibiotic Sensitivity) phage belonging to the Myoviridae family can induce multistep genomic deletion in drug-resistant clinical strains of P. aeruginosa, producing a compromised drug efflux system in the bacterial host. We identified two types of mutant lines in the process: green mutants with SNPs (single nucleotide polymorphisms) and smaller deletions and brown mutants with large (∼250 kbp) genomic deletion. We demonstrated that PIAS used the MexXY-OprM system to initiate the infection. P. aeruginosa clogged PIAS phage infection by either modifying or deleting these receptors. The green mutant gaining phage resistance by SNPs could be overcome by evolved PIASs (E-PIASs) with a mutation in its tail-fiber protein. Characterization of the mutant phages will provide a deeper understanding of phage-host interaction. The coevolutionary process continued with large deletions in the same regions of the bacterial genomes to block the (E-)PIAS infection. These mutants gained phage resistance via either complete loss or substantial modifications of the phage receptor, MexXY-OprM, negating its essential role in antibiotic resistance. In vitro and in vivo studies indicated that combined use of PIAS and antibiotics could effectively inhibit P. aeruginosa growth. The phage can either eradicate bacteria or induce antibiotic sensitivity in MDR-resistant clinical strains. We have explored the potential use of combination therapy as an alternative approach against MDR P. aeruginosa infection.},
	keywords = {Combined treatment; bacteriophage therapy; phage resistance; MexXY-OprM efflux system; phage-provoked sequential genomic mutation/deletion},
	year = {2021},
	eissn = {1664-302X},
	orcid-numbers = {Deim, Zoltán/0000-0003-3925-5564; Terhes, Gabriella/0000-0002-7301-9672; Zsoldiné Urbán, Edit/0000-0002-9602-7552; Váczi, Sándor/0000-0002-9642-7126; Pertics, Botond Zsombor/0000-0002-1734-1632; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:32471534,
	title = {Phage-Induced Antibiotic Sensitivity of Multidrug Resistant Pseudomonas Aeruginosa: A Perspective on Combined Phage-Antibiotic Therapy},
	url = {https://m2.mtmt.hu/api/publication/32471534},
	author = {Koderi Valappil, Sarshad and Deim, Zoltán and Terhes, Gabriella and Zsoldiné Urbán, Edit and Prateek, Shetty and Roland, Patai and György, Schneider and Tamás, Kovács and Rákhely, Gábor},
	journal-iso = {ACTA MICROBIOL IMMUNOL HUNG},
	journal = {ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA},
	volume = {68},
	unique-id = {32471534},
	issn = {1217-8950},
	year = {2021},
	eissn = {1588-2640},
	pages = {47-47},
	orcid-numbers = {Deim, Zoltán/0000-0003-3925-5564; Terhes, Gabriella/0000-0002-7301-9672; Zsoldiné Urbán, Edit/0000-0002-9602-7552; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:31282739,
	title = {Identification of a novel archaea virus, detected in hydrocarbon polluted Hungarian and Canadian samples},
	url = {https://m2.mtmt.hu/api/publication/31282739},
	author = {Molnár, János and Magyar, Balázs and Schneider, György and Laczi, Krisztián and Koderi Valappil, Sarshad and Kovács, Árpád L and Nagy, Ildikó K and Rákhely, Gábor and Kovács, Tamás},
	doi = {10.1371/journal.pone.0231864},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {15},
	unique-id = {31282739},
	issn = {1932-6203},
	abstract = {Metagenomics is a helpful tool for the analysis of unculturable organisms and viruses. Viruses that target bacteria and archaea play important roles in the microbial diversity of various ecosystems. Here we show that Methanosarcina virus MV (MetMV), the second Methanosarcina sp. virus with a completely determined genome, is characteristic of hydrocarbon pollution in environmental (soil and water) samples. It was highly abundant in Hungarian hydrocarbon polluted samples and its genome was also present in the NCBI SRA database containing reads from hydrocarbon polluted samples collected in Canada, indicating the stability of its niche and the marker feature of this virus. MetMV, as the only currently identified marker virus for pollution in environmental samples, could contribute to the understanding of the complicated network of prokaryotes and their viruses driving the decomposition of environmental pollutants.},
	year = {2020},
	eissn = {1932-6203},
	orcid-numbers = {Laczi, Krisztián/0000-0002-9399-7406; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:31272367,
	title = {Identification of a newly isolated lytic bacteriophage against K24 capsular type, carbapenem resistant Klebsiella pneumoniae isolates},
	url = {https://m2.mtmt.hu/api/publication/31272367},
	author = {Horváth, Marianna and Kovács, Tamás and Koderi Valappil, Sarshad and Ábrahám, Hajnalka and Rákhely, Gábor and Schneider, György},
	doi = {10.1038/s41598-020-62691-8},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {10},
	unique-id = {31272367},
	issn = {2045-2322},
	year = {2020},
	eissn = {2045-2322},
	orcid-numbers = {Rákhely, Gábor/0000-0003-2557-3641}
}

@inproceedings{MTMT:30736148,
	title = {A potential application of Pseudomonas aeruginosa phages in water treatments},
	url = {https://m2.mtmt.hu/api/publication/30736148},
	author = {Koderi Valappil, Sarshad and Deim, Zoltán and Péter, Soma Bor and György, Schneider and Kovács, Tamás and Rákhely, Gábor},
	booktitle = {II. Sustainable Raw Materials Conference Book - International Project Week and Scientific Conference},
	unique-id = {30736148},
	year = {2019},
	pages = {183-185},
	orcid-numbers = {Deim, Zoltán/0000-0003-3925-5564; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:30732697,
	title = {Porcine circovirus type 3 detection in a Hungarian pig farm experiencing reproductive failures},
	url = {https://m2.mtmt.hu/api/publication/30732697},
	author = {Deim, Zoltán and Dencső, László and Erdélyi, Ildikó and Koderi Valappil, Sarshad and Varga, Csaba and Pósa, Anikó and Makrai, László and Rákhely, Gábor},
	doi = {10.1136/vr.104784},
	journal-iso = {VET REC},
	journal = {VETERINARY RECORD},
	volume = {185},
	unique-id = {30732697},
	issn = {0042-4900},
	year = {2019},
	eissn = {2042-7670},
	pages = {84-84},
	orcid-numbers = {Deim, Zoltán/0000-0003-3925-5564; Varga, Csaba/0000-0002-2678-665X; Pósa, Anikó/0000-0003-2167-2888; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:3346149,
	title = {Characterization of novel lytic bacteriophages against Pseudomonas aeruginosa clinical isolates},
	url = {https://m2.mtmt.hu/api/publication/3346149},
	author = {Koderi Valappil, Sarshad and Deim, Zoltán and Terhes, Gabriella and Zsoldiné Urbán, Edit and Schneider, György and Kovács, Tamás and Rákhely, Gábor},
	journal-iso = {ACTA MICROBIOL IMMUNOL HUNG},
	journal = {ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA},
	volume = {64},
	unique-id = {3346149},
	issn = {1217-8950},
	year = {2017},
	eissn = {1588-2640},
	pages = {186-186},
	orcid-numbers = {Deim, Zoltán/0000-0003-3925-5564; Terhes, Gabriella/0000-0002-7301-9672; Zsoldiné Urbán, Edit/0000-0002-9602-7552; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:3346143,
	title = {COMPARATIVE GENOMICS OF XOP2-LIKE XANTHOMONAS ORYZAE PV. ORYZAE BACTERIOPHAGES},
	url = {https://m2.mtmt.hu/api/publication/3346143},
	author = {Rákhely, Gábor and ILDIKÓ, VARGA and JÁNOS, MOLNÁR and ANNAMÁRIA, GAZDAG and Szűcs, Dominika and ZSOLT, DOFFKAY and Koderi Valappil, Sarshad and SZILVIA, PAPP and RÉKA, PINTÉR and CASIANA, M VERA CRUZ and TÍMEA, VIZI and GYÖRGY, SCHNEIDER and Kovács, Tamás},
	journal-iso = {ACTA MICROBIOL IMMUNOL HUNG},
	journal = {ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA},
	volume = {64},
	unique-id = {3346143},
	issn = {1217-8950},
	year = {2017},
	eissn = {1588-2640},
	pages = {160-161},
	orcid-numbers = {Rákhely, Gábor/0000-0003-2557-3641}
}