Identification of Novel Phage Resistance Mechanisms in Campylobacter jejuni by Comparative Genomics
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Identification of Novel Phage Resistance Mechanisms in Campylobacter jejuni by Comparative Genomics. / Sørensen, Martine C.H.; Gencay, Yilmaz Emre; Fanger, Florian; Chichkova, Mariana A.T.; Mazúrová, Mária; Klumpp, Jochen; Nielsen, Eva M.; Brøndsted, Lone.
In: Frontiers in Microbiology, Vol. 12, 780559, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of Novel Phage Resistance Mechanisms in Campylobacter jejuni by Comparative Genomics
AU - Sørensen, Martine C.H.
AU - Gencay, Yilmaz Emre
AU - Fanger, Florian
AU - Chichkova, Mariana A.T.
AU - Mazúrová, Mária
AU - Klumpp, Jochen
AU - Nielsen, Eva M.
AU - Brøndsted, Lone
N1 - Publisher Copyright: Copyright © 2021 Sørensen, Gencay, Fanger, Chichkova, Mazúrová, Klumpp, Nielsen and Brøndsted.
PY - 2021
Y1 - 2021
N2 - Phages infecting Campylobacter jejuni are considered a promising intervention strategy at broiler farms, yet phage sensitivity of naturally occurring poultry isolates is not well studied. Here, we investigated phage sensitivity and identified resistance mechanisms of C. jejuni strains originating from Danish broilers belonging to the most prevalent MLST (ST) types. Determining plaque formation of 51 phages belonging to Fletchervirus or Firehammervirus showed that 21 out of 31 C. jejuni strains were susceptible to at least one phage. While C. jejuni ST-21 strains encoded the common phase variable O-methyl phosphoramidate (MeOPN) receptor of the Fletchervirus and were only infected by these phages, ST-45 strains did not encode this receptor and were exclusively infected by Firehammervirus phages. To identify internal phage resistance mechanism in ST-21 strains, we performed comparative genomics of two strains, CAMSA2002 sensitive to almost all Fletchervirus phages and CAMSA2038, resistant to all 51 phages. The strains encoded diverse clustered regularly interspaced short palindromic repeats (CRISPR) spacers but none matched the tested phages. Sequence divergence was also observed in a predicted SspE homolog and putative restriction modification systems including a methyl-specific McrBC endonuclease. Furthermore, when mcrB was deleted, CAMSA2038 became sensitive to 17 out of 43 phages, three being Firehammervirus phages that otherwise did not infect any ST-21 strains. Yet, 16 phages demonstrated significantly lower efficiencies of plating on the mcrB mutant suggesting additional resistance mechanism still restricting phage propagation in CAMSA2038. Thus, our work demonstrates that C. jejuni isolates originating from broilers may have acquired several resistance mechanisms to successfully prevent phage infection in their natural habitat.
AB - Phages infecting Campylobacter jejuni are considered a promising intervention strategy at broiler farms, yet phage sensitivity of naturally occurring poultry isolates is not well studied. Here, we investigated phage sensitivity and identified resistance mechanisms of C. jejuni strains originating from Danish broilers belonging to the most prevalent MLST (ST) types. Determining plaque formation of 51 phages belonging to Fletchervirus or Firehammervirus showed that 21 out of 31 C. jejuni strains were susceptible to at least one phage. While C. jejuni ST-21 strains encoded the common phase variable O-methyl phosphoramidate (MeOPN) receptor of the Fletchervirus and were only infected by these phages, ST-45 strains did not encode this receptor and were exclusively infected by Firehammervirus phages. To identify internal phage resistance mechanism in ST-21 strains, we performed comparative genomics of two strains, CAMSA2002 sensitive to almost all Fletchervirus phages and CAMSA2038, resistant to all 51 phages. The strains encoded diverse clustered regularly interspaced short palindromic repeats (CRISPR) spacers but none matched the tested phages. Sequence divergence was also observed in a predicted SspE homolog and putative restriction modification systems including a methyl-specific McrBC endonuclease. Furthermore, when mcrB was deleted, CAMSA2038 became sensitive to 17 out of 43 phages, three being Firehammervirus phages that otherwise did not infect any ST-21 strains. Yet, 16 phages demonstrated significantly lower efficiencies of plating on the mcrB mutant suggesting additional resistance mechanism still restricting phage propagation in CAMSA2038. Thus, our work demonstrates that C. jejuni isolates originating from broilers may have acquired several resistance mechanisms to successfully prevent phage infection in their natural habitat.
KW - bacteriophage
KW - Campylobacter jejuni
KW - comparative genomics
KW - McrBC
KW - MLST (multilocus sequence typing)
KW - phage resistance
KW - phage sensitivity
KW - restriction modification system
U2 - 10.3389/fmicb.2021.780559
DO - 10.3389/fmicb.2021.780559
M3 - Journal article
C2 - 34970240
AN - SCOPUS:85121976983
VL - 12
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 780559
ER -
ID: 289393759