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RLP, a bacteriophage of the family Podoviridae, rescues mice from bacteremia caused by multi-drug-resistant Pseudomonas aeruginosa

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Abstract

Antimicrobial resistance is a serious threat to public health around the globe. According to the World Health Organization, there will be a return to the pre-penicillin era by 2050 if no new antimicrobials are discovered. It is therefore necessary to find new antimicrobials and alternatives. Pseudomonas aeruginosa exhibits resistance against many antibiotics and causes a variety of infections in immunocompromised individuals and especially in those with burn wounds and lung infections. Bacteriophage RLP against P. aeruginosa strain PA-1 was isolated from the Ravi River near Lahore. It showed marked stability at different pH values and temperatures, with the maximum storage stability at 4 °C. It demonstrated the ability to inhibit bacterial growth for up to 20 h, replicated in 25 min, and produced 154 virions per infected cell. RLP showed a broad host range, infecting 50% (19/38) of the multiple-drug-resistant (MDR) P. aeruginosa strains that were tested. The 43-kbp-long genome of RLP is a double-stranded DNA molecule that encodes 56 proteins in total: 34 with known functions, and 22 with no homolog in the gene databases. A cascade system of lytic machinery is also present in the form of four genes (R/z, R/z1, holin and endolysin). Therapeutic studies of RLP in bacteremic mice infected with P. aeruginosa strain PA-1 demonstrated a 92% survival rate in the treated group compared with 7.4% in the untreated group, and this result was statistically significant. Based on its physiological and genetic properties, ability to cause a reduction in bacterial growth in vitro and its in vivo therapeutic efficacy, RLP could be a good candidate for use in phage therapy.

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Author information

Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, 54590, Pakistan

    Iqbal Ahmad Alvi, Muhammad Asif, Rabia Tabassum, Rehan Aslam, Zaigham Abbas & Shafiq ur Rehman

  2. Department of Microbiology, Hazara University, Mansehra, 21300, Pakistan

    Iqbal Ahmad Alvi

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  1. Iqbal Ahmad Alvi
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  2. Muhammad Asif
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  4. Rehan Aslam
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  6. Shafiq ur Rehman
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Contributions

The research work was conducted as a part of the PhD research of Iqbal Ahmad Alvi. Shafiq Ur Rehman and Iqbal Ahmad Alvi designed the study; Iqbal Ahmad Alvi and Muhammad Asif performed the in vitro studies; Iqbal Ahmad Alvi, Rehan Aslam and Zaigham Abbas performed animal model studies; and Iqbal Ahmad Alvi, Muhammad Asif, Rabia Tabassum and Shafiq Ur Rehman perfomed the pharmacokinetics studies, compiled the data and prepared the manuscript.

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Correspondence to Shafiq ur Rehman.

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Handling Editor: T. K. Frey.

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The 16S rRNA sequence of the bacterial strain (Pseudomonas aeruginosa strain PA-1) was submitted to NCBI GenBank with accession number MG763232. The whole genome sequence of bacteriophage RLP was submitted to NCBI GenBank with accession number MH979674.

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Alvi, I.A., Asif, M., Tabassum, R. et al. RLP, a bacteriophage of the family Podoviridae, rescues mice from bacteremia caused by multi-drug-resistant Pseudomonas aeruginosa. Arch Virol 165, 1289–1297 (2020). https://doi.org/10.1007/s00705-020-04601-x

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