Isolation, Characterization, Genome Analysis and Host Resistance Development of Two Novel Lastavirus Phages Active against Pandrug-Resistant Klebsiella pneumoniae

is a global health threat and bacteriophages are a potential solution in combating pandrug-resistant infections. Two lytic phages, LASTA and SJM3, active against several pandrug-resistant, nosocomial strains of were isolated and characterized. Their host range is narrow and latent period is particul...

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Published in:Viruses 2023-02, Vol.15 (3), p.628
Main Authors: Obradović, Mina, Malešević, Milka, Di Luca, Mariagrazia, Kekić, Dušan, Gajić, Ina, McAuliffe, Olivia, Neve, Horst, Stanisavljević, Nemanja, Vukotić, Goran, Kojić, Milan
Format: Article
Language:English
Subjects:
Antibiotics
Antimicrobial agents
Bacteriophages
Biofilms
Drug resistance
E coli
Genome, Viral
Genomes
Host range
Host Specificity
Infections
Klebsiella pneumoniae
Klebsiella pneumoniae - genetics
Laboratories
Lastavirus
Latent period
Lysogeny
lytic bacteriophage
Microscopy
Multidrug resistant organisms
Mutation
New genera
Nucleotide sequence
phage resistance
Phages
Polyethylene glycol
Propagation
Public health
Sequence analysis
tail fiber
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Summary:is a global health threat and bacteriophages are a potential solution in combating pandrug-resistant infections. Two lytic phages, LASTA and SJM3, active against several pandrug-resistant, nosocomial strains of 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 . 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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v15030628