Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae
Autori
Obradović, MinaMalešević, Milka
Di Luca, Mariagrazia
Kekić, Dušan
Gajić, Ina
McAuliffe, Olivia
Neve, Horst
Stanisavljević, Nemanja
Vukotić, Goran
Kojić, Milan
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Klebsiella pneumoniae is a global health threat and bacteriophages are a potential solution in combating pandrug-resistant K. pneumoniae infections. Two lytic phages, LASTA and SJM3, active against several pandrug-resistant, nosocomial strains of K. pneumoniae were isolated and characterized. Their host range is narrow and latent period is particularly long; however, their lysogenic nature was refuted using both bioinformatic and experimental approaches. Genome sequence analysis clustered them with only two other phages into the new genus Lastavirus. Genomes of LASTA and SJM3 differ in only 13 base pairs, mainly located in tail fiber genes. Individual phages, as well as their cocktail, demonstrated significant bacterial reduction capacity in a time-dependent manner, yielding up to 4 log reduction against planktonic, and up to 2.59 log on biofilm-embedded, cells. Bacteria emerging from the contact with the phages developed resistance and achieved numbers comparable to the growth control... after 24 h. The resistance to the phage seems to be of a transient nature and varies significantly between the two phages, as resistance to LASTA remained constant while resensitization to SJM3 was more prominent. Albeit with very few differences, SJM3 performed better than LASTA overall; however, more investigation is needed in order to consider them for therapeutic application.
Ključne reči:
Klebsiella pneumoniae / Lastavirus / lytic bacteriophage / phage resistance / tail fiberIzvor:
Viruses, 2023, 15, 3, 628-Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200042 (Univerzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo) (RS-MESTD-inst-2020-200042)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200178 (Univerzitet u Beogradu, Biološki fakultet) (RS-MESTD-inst-2020-200178)
- Serbian-Italian bilateral project for exchange of researchers 2019-2021 (code RS19MO07)
- FEMS Grant ID#: FEMSRG-2016-0118 provided by Federation of European Microbiological Societies, and by Teagasc (ref. 0027MD)
- MDL was also supported by “PRA –Progetti di Ricerca di Ateneo” (Institutional Research Grants) -Project no. PRA_2020_32 “I batteriofagi: un’alternativa agli antibiotici contro batteri multi-resistenti in comunità sessili
Napomena:
- Related to supp. material: https://imagine.imgge.bg.ac.rs/handle/123456789/2072
Povezane informacije:
- Povezani sadržaj
https://imagine.imgge.bg.ac.rs/handle/123456789/2072
Kolekcije
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Obradović, Mina AU - Malešević, Milka AU - Di Luca, Mariagrazia AU - Kekić, Dušan AU - Gajić, Ina AU - McAuliffe, Olivia AU - Neve, Horst AU - Stanisavljević, Nemanja AU - Vukotić, Goran AU - Kojić, Milan PY - 2023 UR - https://www.mdpi.com/1999-4915/15/3/628 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2065 AB - Klebsiella pneumoniae is a global health threat and bacteriophages are a potential solution in combating pandrug-resistant K. pneumoniae infections. Two lytic phages, LASTA and SJM3, active against several pandrug-resistant, nosocomial strains of K. pneumoniae were isolated and characterized. Their host range is narrow and latent period is particularly long; however, their lysogenic nature was refuted using both bioinformatic and experimental approaches. Genome sequence analysis clustered them with only two other phages into the new genus Lastavirus. Genomes of LASTA and SJM3 differ in only 13 base pairs, mainly located in tail fiber genes. Individual phages, as well as their cocktail, demonstrated significant bacterial reduction capacity in a time-dependent manner, yielding up to 4 log reduction against planktonic, and up to 2.59 log on biofilm-embedded, cells. Bacteria emerging from the contact with the phages developed resistance and achieved numbers comparable to the growth control after 24 h. The resistance to the phage seems to be of a transient nature and varies significantly between the two phages, as resistance to LASTA remained constant while resensitization to SJM3 was more prominent. Albeit with very few differences, SJM3 performed better than LASTA overall; however, more investigation is needed in order to consider them for therapeutic application. T2 - Viruses T1 - Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae IS - 3 SP - 628 VL - 15 DO - 10.3390/v15030628 ER -
@article{ author = "Obradović, Mina and Malešević, Milka and Di Luca, Mariagrazia and Kekić, Dušan and Gajić, Ina and McAuliffe, Olivia and Neve, Horst and Stanisavljević, Nemanja and Vukotić, Goran and Kojić, Milan", year = "2023", abstract = "Klebsiella pneumoniae is a global health threat and bacteriophages are a potential solution in combating pandrug-resistant K. pneumoniae infections. Two lytic phages, LASTA and SJM3, active against several pandrug-resistant, nosocomial strains of K. pneumoniae were isolated and characterized. Their host range is narrow and latent period is particularly long; however, their lysogenic nature was refuted using both bioinformatic and experimental approaches. Genome sequence analysis clustered them with only two other phages into the new genus Lastavirus. Genomes of LASTA and SJM3 differ in only 13 base pairs, mainly located in tail fiber genes. Individual phages, as well as their cocktail, demonstrated significant bacterial reduction capacity in a time-dependent manner, yielding up to 4 log reduction against planktonic, and up to 2.59 log on biofilm-embedded, cells. Bacteria emerging from the contact with the phages developed resistance and achieved numbers comparable to the growth control after 24 h. The resistance to the phage seems to be of a transient nature and varies significantly between the two phages, as resistance to LASTA remained constant while resensitization to SJM3 was more prominent. Albeit with very few differences, SJM3 performed better than LASTA overall; however, more investigation is needed in order to consider them for therapeutic application.", journal = "Viruses", title = "Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae", number = "3", pages = "628", volume = "15", doi = "10.3390/v15030628" }
Obradović, M., Malešević, M., Di Luca, M., Kekić, D., Gajić, I., McAuliffe, O., Neve, H., Stanisavljević, N., Vukotić, G.,& Kojić, M.. (2023). Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae. in Viruses, 15(3), 628. https://doi.org/10.3390/v15030628
Obradović M, Malešević M, Di Luca M, Kekić D, Gajić I, McAuliffe O, Neve H, Stanisavljević N, Vukotić G, Kojić M. Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae. in Viruses. 2023;15(3):628. doi:10.3390/v15030628 .
Obradović, Mina, Malešević, Milka, Di Luca, Mariagrazia, Kekić, Dušan, Gajić, Ina, McAuliffe, Olivia, Neve, Horst, Stanisavljević, Nemanja, Vukotić, Goran, Kojić, Milan, "Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae" in Viruses, 15, no. 3 (2023):628, https://doi.org/10.3390/v15030628 . .