Transcriptome Analyses of Prophage in Mediating Persistent Methicillin-Resistant Endovascular Infection

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2022 Sep 23

PMID 36140695

Authors

Yi Li

Liang Chen

Fengli Zhu

Arnold S Bayer

Yan Q Xiong

Affiliations

Soon will be listed here.

Abstract

Persistent methicillin-resistant (MRSA) endovascular infections represent a significant subset of infections and correlate with exceptionally high mortality. We have recently demonstrated that the lysogenization of prophage ϕSA169 from a clinical persistent MRSA bacteremia isolate (300-169) into a clinical resolving bacteremia MRSA isolate (301-188) resulted in the acquisition of well-defined in vitro and in vivo phenotypic and genotypic profiles related to persistent outcome. However, the underlying mechanism(s) of this impact is unknown. In the current study, we explored the genetic mechanism that may contribute to the ϕSA169-correlated persistence using RNA sequencing. Transcriptomic analyses revealed that the most significant impacts of ϕSA169 were: (i) the enhancement of fatty acid biosynthesis and purine and pyrimidine metabolic pathways; (ii) the repression of galactose metabolism and phosphotransferase system (PTS); and (iii) the down-regulation of the mutual prophage genes in both 300-169 and 301-188 strains. In addition, the influence of different genetic backgrounds between 300-169 and 301-188 might also be involved in the persistent outcome. These findings may provide targets for future studies on the persistence of MRSA.

References

El Haddad L, Moineau S . Characterization of a Novel Panton-Valentine leukocidin (PVL)-encoding staphylococcal phage and its naturally PVL-lacking variant. Appl Environ Microbiol. 2013; 79(8):2828-32. PMC: 3623202. DOI: 10.1128/AEM.03852-12. View

Sause W, Balasubramanian D, Irnov I, Copin R, Sullivan M, Sommerfield A . The purine biosynthesis regulator PurR moonlights as a virulence regulator in . Proc Natl Acad Sci U S A. 2019; 116(27):13563-13572. PMC: 6613142. DOI: 10.1073/pnas.1904280116. View

Kanehisa M, Sato Y, Kawashima M . KEGG mapping tools for uncovering hidden features in biological data. Protein Sci. 2021; 31(1):47-53. PMC: 8740838. DOI: 10.1002/pro.4172. View

Li L, Wang G, Li Y, Francois P, Bayer A, Chen L . Impact of the Novel Prophage ϕSA169 on Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection. mSystems. 2020; 5(3). PMC: 7329321. DOI: 10.1128/mSystems.00178-20. View

Li L, Yeaman M, Bayer A, Xiong Y . Phenotypic and Genotypic Characteristics of Methicillin-Resistant (MRSA) Related to Persistent Endovascular Infection. Antibiotics (Basel). 2019; 8(2). PMC: 6627527. DOI: 10.3390/antibiotics8020071. View

Abdelhady W, Bayer A, Seidl K, Moormeier D, Bayles K, Cheung A . Impact of vancomycin on sarA-mediated biofilm formation: role in persistent endovascular infections due to methicillin-resistant Staphylococcus aureus. J Infect Dis. 2014; 209(8):1231-40. PMC: 3969550. DOI: 10.1093/infdis/jiu007. View

Li L, Wang G, Cheung A, Abdelhady W, Seidl K, Xiong Y . MgrA Governs Adherence, Host Cell Interaction, and Virulence in a Murine Model of Bacteremia Due to Staphylococcus aureus. J Infect Dis. 2019; 220(6):1019-1028. PMC: 6688059. DOI: 10.1093/infdis/jiz219. View

Chai Y, Beauregard P, Vlamakis H, Losick R, Kolter R . Galactose metabolism plays a crucial role in biofilm formation by Bacillus subtilis. mBio. 2012; 3(4):e00184-12. PMC: 3419520. DOI: 10.1128/mBio.00184-12. View

Hernandez D, Seidl K, Corvaglia A, Bayer A, Xiong Y, Francois P . Genome Sequences of Sequence Type 45 (ST45) Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia Strain 300-169 and ST45 Resolving MRSA Bacteremia Strain 301-188. Genome Announc. 2014; 2(2). PMC: 3953194. DOI: 10.1128/genomeA.00174-14. View

10.

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

11.

Payne D, Warren P, Holmes D, Ji Y, Lonsdale J . Bacterial fatty-acid biosynthesis: a genomics-driven target for antibacterial drug discovery. Drug Discov Today. 2001; 6(10):537-544. DOI: 10.1016/s1359-6446(01)01774-3. View

12.

Cui L, Isii T, Fukuda M, Ochiai T, Neoh H, Camargo I . An RpoB mutation confers dual heteroresistance to daptomycin and vancomycin in Staphylococcus aureus. Antimicrob Agents Chemother. 2010; 54(12):5222-33. PMC: 2981288. DOI: 10.1128/AAC.00437-10. View

13.

Gera K, Le T, Jamin R, Eichenbaum Z, McIver K . The phosphoenolpyruvate phosphotransferase system in group A Streptococcus acts to reduce streptolysin S activity and lesion severity during soft tissue infection. Infect Immun. 2014; 82(3):1192-204. PMC: 3957985. DOI: 10.1128/IAI.01271-13. View

14.

Fowler Jr V, Miro J, Hoen B, Cabell C, Abrutyn E, Rubinstein E . Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA. 2005; 293(24):3012-21. DOI: 10.1001/jama.293.24.3012. View

15.

Li L, Abdelhady W, Donegan N, Seidl K, Cheung A, Zhou Y . Role of Purine Biosynthesis in Persistent Methicillin-Resistant Staphylococcus aureus Infection. J Infect Dis. 2018; 218(9):1367-1377. PMC: 6151072. DOI: 10.1093/infdis/jiy340. View

16.

Kondo K, Kawano M, Sugai M . Distribution of Antimicrobial Resistance and Virulence Genes within the Prophage-Associated Regions in Nosocomial Pathogens. mSphere. 2021; 6(4):e0045221. PMC: 8386436. DOI: 10.1128/mSphere.00452-21. View

17.

Fernandez L, Gonzalez S, Campelo A, Martinez B, Rodriguez A, Garcia P . Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus. Sci Rep. 2017; 7:40965. PMC: 5244418. DOI: 10.1038/srep40965. View

18.

Novick R . Mobile genetic elements and bacterial toxinoses: the superantigen-encoding pathogenicity islands of Staphylococcus aureus. Plasmid. 2003; 49(2):93-105. DOI: 10.1016/s0147-619x(02)00157-9. View

19.

Wang J, Soisson S, Young K, Shoop W, Kodali S, Galgoci A . Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature. 2006; 441(7091):358-61. DOI: 10.1038/nature04784. View

20.

Miallau L, Hunter W, McSweeney S, Leonard G . Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism. J Biol Chem. 2007; 282(27):19948-57. DOI: 10.1074/jbc.M701480200. View