Genomic insights into multidrug-resistance and virulence in a vancomycin-resistant Staphylococcus aureus strain VR480

Nguyen Quang Huy, Nguyen Thai Son, Nguyen Thai Uyen Thu, Nguyen Thuy Duong, Tran Thi Thanh Tam
Author affiliations


  • Nguyen Quang Huy University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam
  • Nguyen Thai Son University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam
  • Nguyen Thai Uyen Thu University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam
  • Nguyen Thuy Duong University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam
  • Tran Thi Thanh Tam University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Ha Noi, Vietnam



Antibiotic resistance, protein interaction network, Staphylococcus aureus, virulence, vancomycin resistance, whole genome sequencing.


Vancomycin-resistant Staphylococcus aureus (VRSA), a “high priority antibiotic-resistant pathogen”, is emerging and threatening global health. Nevertheless, molecular mechanisms associated with virulence and multidrug resistance in VRSA are not fully investigated particularly in low- and middle-income countries. Here, for the first time, the complete genome of a VRSA strain VR480 isolated from a Vietnamese patient was generated by the combination of long- and short-read sequencing technologies. The VRSA strain VR480 was a multidrug-resistant phenotype with resistance to at least one antibiotic belonging to beta lactams, quinolones, lincomycin, oxazolidinones, tetracyclines, glycylcyclines, macrolide/lincosamide/streptogramin, nitrofurans, rifamycins, sulfonamides and glycopeptides. This strain was classified as vancomycin resistance (MIC ≥  32 μg/mL). VRSA strain VR480 belonged to sequence type ST2779 and carried the SCCmec type II(2A). The VRSA strain VR480 genome contains five resistance mutations in genes. gyrA S84L, parC S80F, parE D432N, fusA L461K and glpT W355Stop, and eleven antibiotic resistant genes including mecA, mecR, mecI, tetM, tet38, mepA, lmrS, ant(9), ermA, fosB and catA. This strain possesses various virulence factors associated with adherence, biofilm formation, colonization, invasion, anti-phagocytosis and toxicity that promote the infection and pathogenesis. Protein interaction network analysis revealed five clusters consisting of known and putative virulence proteins. Furthermore, epimerase, EssC, IcaA, SplA and Ssl1 were the key proteins within each cluster. This study raises a warning about the circulation and dissemination of VRSA in Vietnam. The key proteins would be potential targets for the development of anti-virulent agents to combat the VRSA infection.


Download data is not yet available.


Metrics Loading ...


WHO, 2017. WHO publishes list of bacteria for which new antibiotics are urgently needed ( Accessed: 20/03/2024.

Santajit S. and Indrawattana N., 2016. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. Biomed Res Int, 2016: 2475067.

Tong S. Y., Davis J. S., Eichenberger E., Holland T. L., Fowler V. G., 2015. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev, 28(3): 603−61.

Lee A., Lencastre H. D., Garau H., Kluytmans J., Malhotra-Kumar S., Peschel A., Harbarth S, 2018. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers, 4: 18033.

Turner N. A., Sharma-Kuinkel B. K., Maskarinec S. A., Eichenberger E. M., Shah P. P., Carugati M., Holland T. L., Fowler V. G., 2019. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol, 17: 203–218.

Chen C. J. and Huang Y. C., 2014. New epidemiology of Staphylococcus aureus infection in Asia. Clin Microbiol Infect, 20(7): 605−23.

Köck R., Becker K., Cookson B., Gemert-Pijnen J. E., Harbarth S., Kluytmans J., Mielke M., Peters G., Skov R. L., Struelens M. J., Tacconelli E., Navarro T. A., Witte W., Friedrich A. W., 2010. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill, 15(41): 19688.

Shariati A., Dadashi M., Moghadam M. T., Belkum V. A., Yaslianifard S., Darban-Sarokhalil D., 2020. Global prevalence and distribution of vancomycin resistant, vancomycin intermediate and heterogeneously vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis. Sci Rep, 10(1): 12689.

Gardete S., Tomasz A., 2014. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest, 124(7): 2836–2840.

McGuinness W. A., Malachowa N., DeLeo F. R., 2017. Vancomycin Resistance in Staphylococcus aureus. Yale J Biol Med, 90(2): 269–281.

Stogios P. J. and Savchenko A., 2020. Molecular mechanisms of vancomycin resistance. Protein Sci, 29(3): 654−669.

Monistero V., Barberio A., Biscarini F., Cremonesi P., Castiglioni B., Graber H. U., Bottini E., Ceballos-Marquez A., Kroemker V., Petzer I. M., Pollera C., Santisteban C., Dantos M. V., Bronzo V., Piccinini R., Re G., Cocchi M., Moroni P., 2020. Different distribution of antimicrobial resistance genes and virulence profiles of Staphylococcus aureus strains isolated from clinical mastitis in six countries, J Dai Sci, 103(4): 3431−3446.

Cong Y., Yang S., Rao X., 2020. Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features. J Adv Res, 21: 169−176.

Phu V. D, Wertheim H. F., Larsson M., Nadjm B., Dinh Q. D., Nilsson L. E., Rydell U., Le T. T., Trinh S. H., Pham H. M., Tran C. T., Doan H. T., Tran N. T., Le N. D., Huynh N. V., Tran T. P., Tran B. D., Nguyen S. T., Pham T. T., Dang T. Q., Nguyen C. V., Lam Y. M., Thwaites G., Nguyen V. K, Hanberger H., 2016. Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units. PLoS One, 11(1): e0147544.

Le N. K., Wertheim H. F., Vu P. D., Khu D. T. K., Le H. T., Hoang B. T. N., Vo V. T., Lam Y. M., Vu D. T. V., Nguyen T. H., Thai T. Q., Nilsson L. E., Rydell U., Nguyen K. V., Nadjm B., Clarkson L., Hanberger H., Larsson M., 2016. High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: A multi-centre point prevalence survey. Medicine (Baltimore), 95(27): e4099.

Vu T. V. D., Choisy M., Do T. T. N., Nguyen V. M. H., Campbell J. I., Le T. H., Nguyen V. T., Wertheim H. F. L., Pham N. T., Nguyen V. K., Doorn H. R., the VINARES consortium., 2021. Antimicrobial susceptibility testing results from 13 hospitals in Viet Nam: VINARES 2016–2017. Antimicrob Resist Infect Control, 10(78).

Nguyen V. A., Le H. L. H., Vu H. L., Nguyen T. H. V, Pham Q. H., Le V. H., Nguyen T. S., Le T. H., Dinh V. H., Hoang T. K., Le N. M., Nguyen H. V., Nguyen D. H., Pham N. V., Ta B. T., Tran V. T., Le H. H., 2024. Antimicrobial resistance patterns of Staphylococcus aureus isolated at a general hospital in Vietnam between 2014 and 2021, Dovepress, 2024: 259−273.

Jahanshahi A., Zeighami H., Haghi F., 2018. Molecular Characterization of Methicillin and Vancomycin Resistant Staphylococcus aureus Strains Isolated from Hospitalized Patients. Microb Drug Resist, 24(10): 1529−1536.

Kim E. S., Bae I. G., Cho J. E., Choi Y. J., Kim I. H., Kang G. S., Sin H. Y., Song K. H., Park C., Lee D. G., Kim M., Park K. U., Kim H. B., 2016. Clinical and Molecular Characterization of Invasive Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Infections in Korean Hospitals. J Clin Microbiol, 54(3): 760−763.

Muzammil I., Ljaz M., Saleem M. H., Ali M. M., 2023. Molecular characterization of vancomycin-resistant Staphylococcus aureus isolated from bovine milk. Zoonoses Public Health, 70(5): 420−433.

Nguyen T. S., Vu T. T. H., Vu T. K. L., Do T. Q. N., Tran T. H. A., Tang T. N., Le N. M. H., Tran Q. B., 2019. First Report on Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Isolates in Children Admitted to Tertiary Hospitals in Vietnam. J Microbiol Biotechnol, 29(9): 1460−1469.

Hoang D. P., Tran T. T. T., Le T. T. H., Nguyen T. K. O., Vu D. H. L., Kieu D. H., Banuls A-L, Nguyen Q. H., 2023. Molecular characterization of methicillin-resistant Staphylococcus aureus strain BM85 isolated from a Vietnamese patient with blood stream infection. Vietnam Journal of Biotechnology, 21(1): 35−44.

Sherathiya V. N., Schaid M. D., Seiler J. L., Lopez G. C., Lerner T. N., 2021. GuPPy, a Python toolbox for the analysis of fiber photometry data. Sci Rep, 11(1): 24212.

Ahmed B. O., Elmekki A. M., Omer E. E., Elhassan M., 2014. Molecular detection of methicillin-resistant Staphylococcus aureus in patients with urinary tract infections in Khartoum State. J. Sci. Technol, 15: 1–8.

Clark N., Cooksey R. C., Hill B. C., Swenson J. M., Tenover F. C., 1993. Characterization of glycopeptide-resistant enterococci from U.S. hospitals. Antimicrob Agents Chemother. 37(11): 2311−2317.

He Y-H., Ruan G-J., Hao H. H., Xue F. F., Ma Y-K., Zhu S-N., Zheng B., 2020. Real-time PCR for the rapid detection of vanA, vanB and vanM genes. Journal of Microbiology, Immunology and Infection, 53(5): 746−750.

Wouter D. C., Svenn D., Darrin T. S., Marc C., Christine V. B., 2018, NanoPack: visualizing and processing long-read sequencing data. Bioinformatics, 34(15): 2666–2669.

Wick R. R., Judd L. M., Gorrie C. L., Holt K. E., 2017. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 13(6): e1005595.

Hayer J., Dainat J., Marcy E., Banuls A-L., 2023. Baargin: a Nextflow workflow for the automatic analysis of bacterial genomics data with a focus on Antimicrobial Resistance. Journal of Open Source Software, 8(90): 5397.

Jolley K. A., Bray J. E., Maiden M. C. J., 2018. Open-access bacterial population genomics: BIGSdb software, the website and their applications. Wellcome Open Res., 24(3): 124.

Kaya H., Hasman H., Larsen J., Stegger M., Johannesen T. B., Allesøe R. L., Lemvigh C. K., Aarestrup F. M., Lund O., Larsen A. R., 2018. SCCmecFinder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome mec in Staphylococcus aureus Using Whole-Genome Sequence Data. mSphere, 3(1): e00612–17.

Feldgarden M., Brover V., Gonzalez-Escalona N., Frye J. G., Haendiges J., Haft D. H., Hofmann M., Pettengill J. B., Klimke W., 2021. AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence. Sci Rep, 11: 12728.

Seemann T., 2014. Prokka: rapid prokaryotic genome annotation. Bioinformatics, 30(14): 2068−2069.

Grant J. R., Enns E., Marinier E., Mandal A., Herman E. K., Chen C., Graham M., Domselaar G. V., Stothard P., 2023. Proksee: in-depth characterization and visualization of bacterial genomes. Nucleic Acids Research, 51(W1): W484–W492.

Doncheva N. T., Morris J. H., Gorodkin J., Jensen L. J., 2019. Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data. J Proteome Res, 18(2): 623−632.

Arciola C. R., Campoccia D., Ravaioli S., Montanaro L., 2015. Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects. Front Cell Infect Microbiol, 10(5): 7.

Dasari P., Nordengrün M., Vilhena C., Steil L., Abdurrahman G., Surmann K., Dhople V., Lahrberg J., Bachert C., Skerka C., Völker U., Bröker B. M., Zipfel P. F., 2020. The Protease SplB of Staphylococcus aureus Targets Host Complement Components and Inhibits Complement-Mediated Bacterial Opsonophagocytosis. J Bacteriol, 204(1): e0018421.

Vasquez M. T., Lubkin A., Tamara R. R., Christopher J. D., Keenan A. L., Michael P. J., Victor J. T., 2020. Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes, J Biologic Chemis, 295(50): 17241–17250.

Tam K., Torres V.J., 2019. Staphylococcus aureus Secreted Toxins and Extracellular Enzymes, Microbiol Spectr, 7(2): 10.

Zhao X., Yuan X., Hu M., Zhang Y., Li L., Zhang Q., Yuan X., Wang W., Liu Y., 2021. Prevalence and characterization of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus isolated from bulk tank milk in Shandong dairy farms. Food Control, 125: 107836.

Monteiro A. S., Pinto B. L. S., Monteiro J. M., Ferreira R. M., Ribeiro P. C. S., Bando S. Y., Marques S. G., Silva L. C. N., Neto W. R. N., Ferreira G. F., 2019. Phylogenetic and Molecular Profile of Staphylococcus aureus Isolated from Bloodstream Infections in Northeast Brazil. Microorganisms, 7: 210.

Hafer C., Lin Y., Kornblum J., Lowy F. D., Uhlemann A. C., 2012. Contribution of selected gene mutations to resistance in clinical isolates of vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother. 56(11): 5845–51.

Hiramatsu K., Kayayama Y., Matsuo M., Aiba Y., Saito M., Hishinuma T., Iwamoto A., 2014. Vancomycin-intermediate resistance in Staphylococcus aureus. Journal of Global Antimicrobial Resistance, 2(4): 213–224.

Cheung G. Y. C., Bae J. S., Otto M., 2021. Pathogenicity and virulence of Staphylococcus aureus. Virulence, 12(1): 547–569.

Shettigar K., Murali T. S., 2020. Virulence factors and clonal diversity of Staphylococcus aureus in colonization and wound infection with emphasis on diabetic foot infection. Eur J Clin Microbiol Infect Dis, 39: 2235–2246.

Cress B. F., Englaender J. A., He W., Kasper D., Linhardt R. J., Koffas M. A. G., 2014. Masquerading microbial pathogens: capsular polysaccharides mimic host-tissue molecules, FEMS Microbiology Reviews, 38(4): 660–697.

Jäger F., Kneuper H., Palmer T., 2018. EssC is a specificity determinant for Staphylococcus aureus type VII secretion. Microbiology, 164(5): 816–820.

Tang A., Caballero A. R., Bierdeman M. A., Marquart M. E., Foster T. J., Monk I. R., O'Callaghan R. J., 2019. Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease. Pathogens, 8(1): 2.

Kadkhoda H., Ghalavand Z., Nikmanesh B., Kodori M., Houri H., Taghizadeh M. D., Karimi B. A., Eslami G., 2020. Characterization of biofilm formation and virulence factors of Staphylococcus aureus isolates from paediatric patients in Tehran, Iran. Iran J Basic Med Sci, 23(5): 691–698.

Paharik A. E., Salgado-Pabon W., Meyerholz D. K., White M. J., Schlievert P. M., Horswill A. R., 2016. The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia. mSphere, 1(5): e00208–16.




How to Cite

Nguyen, Q. H., Nguyen , T. S., Nguyen Thai, U. T., Nguyen , T. D., & Tran Thi , T. T. (2024). Genomic insights into multidrug-resistance and virulence in a vancomycin-resistant <i>Staphylococcus aureus</i> strain VR480. Academia Journal of Biology, 46(2), 133–146.