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Exploitation of a Bacterium-Encoded Lytic Transglycosylase by a Human Oral Lytic Phage To Facilitate Infection

Cen, Lujia and Chang, Yunjie and Bedree, Joseph K. and Ma, Yansong and Zhong, Qiu and Utter, Daniel R. and Dong, Pu-Ting and Lux, Renate and Bor, Batbileg and Liu, Jun and McLean, Jeffrey S. and Le, Shuai and He, Xuesong (2022) Exploitation of a Bacterium-Encoded Lytic Transglycosylase by a Human Oral Lytic Phage To Facilitate Infection. Journal of Virology, In Press . ISSN 0022-538X. doi:10.1128/jvi.01063-22. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20220901-156679900

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Abstract

The evidence for the presence of a diverse and abundant phage population in the host-associated oral microbiome came largely from metagenomic analysis or the observation of virus-like particles within saliva/plaque samples, while the isolation of oral phage and investigation of their interaction with bacterial hosts are limited. Here, we report the isolation of LC001, the first lytic phage targeting oral Schaalia odontolytica. formerly known as Actinomyces odontolyticus) strain XH001. We showed that LC001 attached to and infected surface-grown, but not planktonic, XH001 cells, and it displayed remarkable host specificity at the strain level. Whole-genome sequencing of spontaneous LC001-resistant, surface-grown XH001 mutants revealed that the majority of the mutants carry nonsense or frameshift mutations in XH001 gene APY09_05145 (renamed ltg-1), which encodes a putative lytic transglycosylase (LT). The mutants are defective in LC001 binding, as revealed by direct visualization of the significantly reduced attachment of phage particles to the XH001 spontaneous mutants compared that to the wild type. Meanwhile, targeted deletion of ltg-1 produced a mutant that is defective in LC001 binding and resistant to LC001 infection even as surface-grown cells, while complementation of ltg-1 in the mutant background restored the LC001-sensitive phenotype. Intriguingly, similar expression levels of ltg-1 were observed in surface-grown and planktonic XH001, which displayed LC001-binding and nonbinding phenotypes, respectively. Furthermore, the overexpression of ltg-1 failed to confer an LC001-binding and -sensitive phenotype to planktonic XH001. Thus, our data suggested that rather than directly serving as a phage receptor, ltg-1-encoded LT may increase the accessibility of phage receptor, possibly via its enzymatic activity, by cleaving the peptidoglycan structure for better receptor exposure during peptidoglycan remodeling, a function that can be exploited by LC001 to facilitate infection. IMPORTANCE The evidence for the presence of a diverse and abundant phage population in the host-associated oral microbiome came largely from metagenomic analysis or the observation of virus-like particles within saliva/plaque samples, while the isolation of oral phage and investigation of their interaction with bacterial hosts are limited. Here, we report the isolation of LC001, the first lytic phage targeting oral Schaalia odontolytica. Our study suggested that LC001 may exploit the host bacterium-encoded lytic transglycosylase function to gain access to the receptor, thus facilitating its infection.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1128/jvi.01063-22DOIJournal Article
ORCID:
AuthorORCID
Bedree, Joseph K.0000-0002-3822-649X
Utter, Daniel R.0000-0003-3322-7108
Lux, Renate0000-0003-3253-0471
Bor, Batbileg0000-0002-1797-1730
Liu, Jun0000-0003-3108-6735
McLean, Jeffrey S.0000-0001-9934-5137
Le, Shuai0000-0003-3748-5454
He, Xuesong0000-0002-3333-9188
Additional Information:The study was in part supported by NIH/NIDCR grant no. R01DE023810 (X.H., J.S.M.), R01DE030943 (X.H.), 3R01DE023810-07S1 (X.H., J.L.) and F31DE026057 (J.B.) and the National Natural Science Foundation of China (NSFC grant no. 31870167 to S.L.). We thank Meng Shao for preparing cryo-ET samples with cryo-FIB/SEM at the Liu laboratory at Yale; Y.C. and J.L. were supported by grants R01AI087946 and R01AI132818 from the National Institute of Allergy and Infectious Diseases (NIAID); Cryo-ET data were collected at the Yale Cryo-EM resources and funded in part by the NIH grant 1S10OD023603-01A1.
Funders:
Funding AgencyGrant Number
HHS | NIH | National Institute of Dental and Craniofacial ResearchR01DE023810
HHS | NIH | National Institute of Dental and Craniofacial Research3R01DE023810-07S1
HHS | NIH | National Institute of Dental and Craniofacial ResearchR01DE030943
HHS | NIH | National Institute of Dental and Craniofacial ResearchF31DE026057
National Natural Science Foundation of China31870167
National Institute of Allergy and Infectious Diseases (NIAID)R01AI087946
National Institute of Allergy and Infectious Diseases (NIAID)R01AI132818
NIH1S10OD023603-01A1
DOI:10.1128/jvi.01063-22
Record Number:CaltechAUTHORS:20220901-156679900
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220901-156679900
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:116687
Collection:CaltechAUTHORS
Deposited By: Donna Wrublewski
Deposited On:07 Sep 2022 22:38
Last Modified:07 Sep 2022 22:38

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