Sarshad Koderi Valappil

University of Szeged

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György Schneider

University of Pecs

Tamás Kovács

Enviroinvest Environmental and Biotechnological Corp

Gábor Rákhely

Institute of Biophysics

Zoltán Deim

University of Szeged

Gábor Rákhely

HUN-REN Szegedi Biológiai Kutatóközpont

Ildikó K. Nagy

Enviroinvest Environmental and Biotechnological Corp

János Molnár

American Institute for Economic Research

Gabriella Terhes

University of Szeged

László Dér

Institute of Biophysics

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Hajnalka Ábrahám

University of Pecs

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University of Szeged

Hungarian Academy of Sciences

HUN-REN Szegedi Biológiai Kutatóközpont

Institute of Biophysics

University of Pecs

Hungarian Research Network

Enviroinvest Environmental and Biotechnological Corp

Princeton University

Johns Hopkins University

Magyar Agrár- és Élettudományi Egyetem

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Identification of a novel archaea virus, detected in hydrocarbon polluted Hungarian and Canadian samples

PLoS ONE (2020)

János Molnár B. Magyar György Schneider Krisztián Laczi Sarshad Koderi Valappil

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.

Environmental Pollution

10.1371/journal.pone.0231864

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Porcine circovirus type 3 detection in a Hungarian pig farm experiencing reproductive failures

Veterinary Record (2019)

Zoltán Deim László Dencső Ildikó Erdélyi Sarshad Koderi Valappil Csaba Varga

Porcine circovirus 3 (PCV3) infection has been reported in piglets and sows with porcine dermatitis and nephropathy syndrome, reproductive failure, and cardiac and multisystemic inflammation. Few studies linked PCV3 infection to increased incidence of abortion and weak-born piglets. This is the first report of a detection of PCV3 Hungarian strain in several organs of aborted and weak-born piglets, including the thymus, lymph node, placenta, spleen, kidney and the liver. The tissue tropism of PCV3 in affected litters was analysed using real-time quantitative PCR, and the result showed the highest load of viral DNA in the thymus and lymph nodes. The ORF2 of Hungarian PCV3 strains was 524 nucleotides in length, and the sequence identity to GenBank sequences ranged from 98.5 per cent to 99.2 per cent. The results suggest that PCV3 may have a relevant role in reproductive failure in gilts.

Mesenteric lymph nodes

Circovirus

10.1136/vr.104784

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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

Frontiers in Microbiology (2021)

Sarshad Koderi Valappil Prateek Shetty Zoltán Deim Gabriella Terhes Edit Urbán

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.

Phage therapy

Myoviridae

Efflux

10.3389/fmicb.2021.783722

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Identification of a newly isolated lytic bacteriophage against K24 capsular type, carbapenem resistant Klebsiella pneumoniae isolates

Scientific Reports (2020)

Marianna Horváth Tamás Kovács Sarshad Koderi Valappil Hajnalka Ábrahám Gábor Rákhely

Abstract The increasing incidence of carbapenemase-producing K. pneumoniae strains (CP-Kps) in the last decade has become a serious global healthcare problem. Therapeutic options for the treatment of emerging hospital clones have drastically narrowed and therefore novel approaches must be considered. Here we have isolated and characterized a lytic bacteriophage, named vB_KpnS_Kp13, that was effective against all Verona integron-encoded metallo-β-lactamase (VIM) producing K. pneumoniae isolates originating from hospital samples (urine, blood, sputum and faeces), belonging to the ST15 clonal lineage and expressing the K24 capsule. Morphological characterization of vB_KpnS_Kp13 showed that the newly identified phage belonged to the Siphoviridae family, and phylogenetic analysis showed that it is part of a distinct clade of the Tunavirinae subfamily. Functional analysis revealed that vB_KpnS_Kp13 had relatively short latent period times (18 minutes) compared to other K. pneumoniae bacteriophages and could degrade biofilm by more than 50% and 70% in 24 and 48 hours respectively. Complete in vivo rescue potential of the new phage was revealed in an intraperitoneal mouse model where phages were administered intraperitoneally 10 minutes after bacterial challenge. Our findings could potentially be used to develop specific anti-CP-Kps bacteriophage-based therapeutic strategies against major clonal lineages and serotypes.

Lytic cycle

Phage therapy

Siphoviridae

10.1038/s41598-020-62691-8

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Microfluidic Ecology Unravels the Genetic and Ecological Drivers of T4r Bacteriophage Resistance in E. coli: Insights into Biofilm-Mediated Evolution

Research Square (Research Square) (2024)

Robert H. Austin Krisztina Nagy Sarshad Koderi Valappil Trung V. Phan Shengkai Li

We use a microfluidic ecology which generates non-uniform phage concentration gradients and micro-ecological niches to reveal the importance of time, spatial population structure and collective population dynamics in the de

Molecular Ecology

10.21203/rs.3.rs-4356333/v1

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Complete Genome Sequences of 10 Xanthomonas oryzae pv. oryzae Bacteriophages

Microbiology Resource Announcements (2019)

Tamás Kovács János Molnár Ildikó Varga Ildikó K. Nagy Sarshad Koderi Valappil

Xanthomonas oryzae pv. oryzae is the causative agent of bacterial leaf blight of rice. The application of bacteriophages may provide an effective tool against this bacterium. Here, we report the complete genome sequences of 10 newly isolated OP2-like X. oryzae pv. oryzae bacteriophages.

Xanthomonas

10.1128/mra.00334-19

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Phage infection reinstates antibiotic sensitivity in MDR Pseudomonas aeruginosa

Sarshad Koderi Valappil

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.

Lytic cycle

Phage therapy

Efflux

10.14232/phd.11330

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