Characteristics of Laboratory-Derived Vancomycin-Intermediate Staphylococcus aureus Strains

Sutanya Jongutsa; Suwanna   Trakulsomboon; Srisuda   Pannanusorn; Ruthada  Chanklan; Sudathip Chantorn; Worawat Surarit; Thrissawan Traijitt; Sugunya Utaida

doi:10.59796/jcst.V14N2.2024.21

Authors

Sutanya Jongutsa Microbiology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand & Food and Drug Administration, Ministry of Health, Nonthaburi 11000, Thailand
Suwanna Trakulsomboon Faculty of Allied Health Sciences, Division of Medical Technology, Nakhonratchasima College, Nakhonratchasima 30000, Thailand
Srisuda Pannanusorn Microbiology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand
Ruthada Chanklan Microbiology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand
Sudathip Chantorn Biochemistry and Biology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand
Worawat Surarit Biochemistry and Biology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand
Thrissawan Traijitt Biochemistry and Biology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand
Sugunya Utaida Microbiology group, Department of Biotechnology, Faculty of Science and Technology, Thammasat University, Rangsit Center, Pathum Thani 12121, Thailand

DOI:

https://doi.org/10.59796/jcst.V14N2.2024.21

Keywords:

vancomycin, VISA, whole cell autolysis, cell wall thickening

Abstract

Four clinical vancomycin susceptible Staphylococcus aureus (VSSA) isolates were subjected to selection for the vancomycin-intermediate S. aureus (VISA) phenotype using increasing concentrations of vancomycin. The vancomycin MIC achieved for VISA strains was 7 µg/mL. Population analysis profiles of the bacteria revealed that almost 100% of population growing at 4 µg/mL of vancomycin while some subpopulations were found to be resistant to concentrations ranging from 6 to 9 µg/mL of vancomycin. The results correlated with the AUC ratios for VISA, which ranged from 3.02-3.3 in this study. In the absence of vancomycin in the assay buffer, all the laboratory-derived VISA strains exhibited reduced whole cell autolysis compared to that of their VSSA counterparts. Examination of cell wall morphologies revealed that almost all the laboratory-derived VISA strains had thicker and rougher cell wall surfaces compared to their parental strains. Vancomycin had no remarkable effects on the thickness and roughness of the cell wall of all the laboratory-derived VISA derivatives.

References

Ahmad, N., Ling, L. N., Ghani, M. K. A., & Nawi, S. (2012) The presence of heterogeneous vancomycin-intermediate Staphylococcus aureus (heteroVISA) in a major Malaysian hospital. Medical Journal of Malaysia, 67(3), 269- 273.

Ansari, S., Jha, R. K., Mishra, S. K., Tiwari, B. R., & Asaad, A. M. (2019). Recent advances in Staphylococcus aureus infection: focus on vaccine development. Infection and Drug Resistance, 12, 1243-1255. https://doi.org/10.2147/IDR.S175014

Cafiso, V., Bertuccio, T., Spina, D., Purrello, S., Campanile, F., Di Pietro, C., ... & Stefani, S. (2012). Modulating activity of vancomycin and daptomycin on the expression of autolysis cell-wall turnover and membrane charge genes in hVISA and VISAstrains. PLoS One, 7(1), Article e29573. https://doi.org/10.1371/journal.pone.0029573

Cameron, D. R., Jiang, J. H., Kostoulias, X., Foxwell, D. J., & Peleg, A. Y. (2016). Vancomycin susceptibility in methicillin-resistant Staphylococcus aureus is mediated by YycHI activation of the WalRK essential two-component regulatory system. Scientific Reports, 6(1), Article 30823. https://doi: 10.1038/srep30823

Cázares-Domínguez, V., Cruz-Córdova, A., Ochoa, S. A., Escalona, G., Arellano-Galindo, J., Rodríguez-Leviz, A., ... & Xicohtencatl-Cortes, J. (2015). Vancomycin tolerant, methicillin-resitant Staphylococcus aureus reveals the effects of vancomycin on cell wall thickening. PLoS ONE, 10(3), Article e0118791. https://doi.org/10.1371/journal.pone. 0118791

Chen, H., Xiong, Z., Liu, K., Li, S., Wang, R., Wang, X., ... & Wang, H. (2016). Transcriptional profiling of the two-component regulatory system VraSR in Staphylococcus aureus with low-level vancomycin resistance. International Journal of Antimicrobial Agents, 47, 362-367. https://doi.org/10.1016/j.ijantimicag.2016.02.003

CLSI. (2021). Performance Standards for Antimicrobial Susceptibility Testing M100 (31st ed.). Pennsylvanai, USA. The Clinical and Laboratory Standards Institute.

Cui, J., Zhang, H., Mo, Z., Yu, M., & Liang, Z. (2021). Cell wall thickness and the molecular mechanism of heterogeneous vancomycin-intermediate Staphylococcus aureus. Letters in Applied Microbiology, 76(5), 604-609. https://doi.org/10.1111/lam.13456

Cui, L., Ma, X., Sato, K., Okuma, K., Tenover, F. C., Mamizuka, E. M., ... & Hiramatsu, K. (2003). Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. Journal of Clinical Microbiology, 41(1), 5-14. https://doi.org/10.1128/JCM.41.1.5-14.2003

Doddangoudar, V. C., O'Donoghue, M. M., Chong, E. Y. C., Tsang, D. N. C., & Boost, M. V. (2012). Role of stop codons in development and loss of vancomycin non-susceptibility in methicillin-resistant Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 67(9), 2101-2106. https://doi.org/10.1093/jac/dks171

Falcón, R., Martínez, A., Albert, E., Madrid, S., Oltra, R., Giménez, E., ... & Navarro, D. (2016). High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes. InternationalJournal of Antimicrobial agents, 47(5), 343-350. https://doi.org/10.1016/j.ijantimicag.2016.01.014

Fukutsuji, K., Yamada, S., & Harada, T. (2013). Ultra structural cell wall characteristics of clinical gentamicin-resistant Staphylococcus aureus isolates. Medical Molecular Morphology, 46, 70-76. https://doi.org/10.1007/s00795-013-0009-0

Gajdiss, M., Monk, I. R., Bertsche, U., Kienemund, J., Funk, T., Dietrich, A., ... & Bierbaum, G. (2020). YycH and YycI regulate expression of Staphylococcus aureus autolysins by activation of WalRK phosphorylation. Microorganisms, 8(6), Article 870. https://doi.org/10.3390/microorganisms8060870

Gardete, S & Tomasz, A. (2014). Mechanisms of vancomycin resistance in Staphylococcus aureus. The Journal of Clinical Investigation, 124(7), 2836-2840. https://doi.org/10.1172/JCI68834

Hiramatsu, K., Hanaki, H., Ino, T., Yabuta, K., Oguri, T., & Tenover, F. C. (1997a). Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. Journal of Antimicrobial Agents Chemotherapy, 40(1), 135-136. https://doi.org/10.1093/jac/40.1.135

Hiramatsu, K., Aritaka, N., Hanaki, H., Kawasaki, S., Hosoda, Y., Hori, S., ... & Kobayashi, I. (1997b). Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. The Lancet, 350(9092), 1670-1673. https://doi.org/10.1016/S0140-6736(97)07324-8

Holmes, N. E., Johnson, P. D., & Howden, B. P. (2012). Relationship between vancomycin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, high vancomycin MIC, and outcome in serious S. aureus infections. Journal of Clinical Microbiology, 50(8), 2548-2552. https://doi.org/10.1128/jcm.00775-12

Howden, B. P., Davies, J. K., Johnson, P. D., Stinear, T. P., & Grayson, M. L. (2010). Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clinical Microbiology Reviews, 23, 99-139. https://doi.org/10.1128/cmr.00042-09

Howden, B. P., McEvoy, C. R., Allen, D. L., Chua, K., Gao, W., Harrison, P. F., ... & Stinear, T. P. (2011). Evolution of multidrug resistance during Staphylococcus aureus infection involves mutation of the essential two component regulator WalKR. PLOS Pathogens, 7(11), Article e1002359. https://doi.org/10.1371/journal.ppat.1002359

Hsu, C. Y., Lin, M. H., Chen, C. C., Chien, S. C., Cheng, Y. H., Su, I. N., & Shu, J. C. (2011). Vancomycin promotes the bacterial autolysis, release of extracellular DNA, and biofilm formation in vancomycin-non-susceptible Staphylococcus aureus. FEMS Immunology & Medical Microbiology, 63(2), 236-247. https://doi.org/10.1111/j.1574-695X.2011.00846.x

Hu, J., Ma, X. X., Tian, Y., Pang, L., Cui, L. Z., & Shang, H. (2013). Reduced vancomycin susceptibility found in methicillin-resistant and methicillin-sensitive Staphylococcus aureus clinical isolates in Northeast China. PLoS One, 8(9), Article e73300. https://doi.org/10.1371/journal.pone.0073300

Hyo, Y., Yamada, S., Fukutsuji, K., & Harada, T. (2013). Thickening of the cell wall in a macrolide-resistant Staphylococcus aureus. Medical Molecular Morphology. 46, 217-224. https://doi.org/10.1007/s00795-013-0027-y

Kazimoto, T., Abdulla, S., Bategereza, L., Juma, O., Mhimbira, F., Weisser, M., ... & Becker, S. L. (2018). Causative agents and antimicrobial resistance patterns of human skin and soft tissue infections in Bagamoyo, Tanzania. Acta tropica, 186, 102-106. https://doi.org/10.1016/j.actatropica.2018.07.007

Liu, C., & Chambers, H. F. (2003). Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrobial Agents and Chemotherapy, 47(10), 3040-3045. https://doi.org/10.1128/aac.47.10.3040-3045.2003

Lulitanond, A., Engchanil, C., Chaimanee, P., Vorachit, M., Ito, T., & Hiramatsu, K. (2009). The first vancomycin-intermediate Staphylococcus aureus strains isolated from patients in Thailand. Journal of Clinical Microbiology, 47(7), 2311-2316. https://doi.org/10.1128/jcm.01749-08

Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., & Marusza, W. (2022). Molecular mechanisms of drug resistance in Staphylococcus aureus. International Journal of Molecular Sciences, 23(15), Article 8088. https://doi.org/10.3390/ijms23158088

Mongodin, E., Finan, J., Climo, M. W., Rosato, A., Gill, S., & Archer, G. L. (2003). Microarray transcription analysis of clinical Staphylococcus aureus isolates resistant to vancomycin. Journal of Bacteriology, 185(15), 4638–4643. https://doi.org/10.1128/jb.185.15.4638-4643.2003

Park, J. W., Lee, H., Kim, J. W., & Kim, B. (2019). Characterization of infections with vancomycin-intermediate Staphylococcus aureus (VISA) and Staphylococcus aureus with reduced vancomycin susceptibility in South Korea. Scientific Reports, 9, Article 6236. https://doi.org/10.1038/s41598-019-42307-6

Peng, H., Hu, Q., Shang, W., Yuan, J., Zhang, X., Liu, H., ... & Rao, X. (2017). WalK (S221P), a naturally occurring mutation, confers vancomycin resistance in VISA strain XN108. Journal of Antimicrobial Chemotherapy, 72(4), 1006-1013. https://doi.org/10.1093/jac/dkw518

Peng, H., Rao, Y., Yuan, W., Zheng, Y., Shang, W., Hu, Z., ... & Rao, X. (2018). Reconstruction of the vancomycin-susceptible Staphylococcus aureus phenotype from a vancomycin-intermediate S. aureus XN108. Frontiers in Microbiology, 9, Article 419471. https://doi.org/10.3389/fmicb.2018.02955

Pfeltz, R. F., Singh, V. K., Schmidt, J. L., Batten, M. A., Baranyk, C. S., Nadakavukaren, M. J., ... & Wilkinson, B. J. (2000). Characterization of passage-selected vancomycin-resistant Staphylococcus aureus strains of diverse parental backgrounds. Antimicrobial Agents and Chemotherapy, 44(2), 294-303. https://doi.org/10.1128/aac.44.2.294-303.2000

Sieradzki, K., & Tomasz A. (2006). Inhibition of autolytic system by vancomycin causes mimicry of vancomycin-intermediate Staphylococcus aureus-type resistance, cell concentration dependence of the mic, and antibiotic tolerance in vancomycin-susceptible S. aureus. Antimicrobial Agents and Chemotherapy, 50(2), 527-533. https://doi.org/10.1128/aac.50.2.527-533.2006

Shen, P., Zhou, K., Wang, Y., Song, J., Liu, Y., Zhou, Y., & Xiao, Y. (2019). High prevalence of a globally disseminated hypervirulent clone, Staphylococcus aureus CC121, with reduced vancomycin susceptibility in community settings in China. Journal of Antimicrobial Chemotherapy, 74(9), 2537-2543. https://doi.org/10.1093/jac/dkz232

Shoji, M., Cui, L., Iizuka, R., Komoto, A., Neoh, H. M., Watanabe, Y., ... & Hiramatsu, K. (2011). walK and clpP mutations confer reduced vancomycin susceptibility in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 55(8), 3870-3881. https://doi.org/10.1128/aac.01563-10

Tavernier, S., Sass, A., De Bruyne, M., Baeke, F., De Rycke, R., Crabbé, A., ... & Coenye, T. (2018). Decreased susceptibility of Streptococcus anginosus to vancomycin in a multispecies biofilm is due to increased thickness of the cell wall. Journal of Antimicrobial Chemotherapy, 73(9), 2323-2330. https://doi.org/10.1093/jac/dky216

Utaida, S., Dunman, P. M., Macapagal, D., Murphy, E., Projan, S. J., Singh, V. K., ... & Wilkinson, B. J. (2003). Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell wall stress stimulon. Microbiology, 149(10), 2719-2732. https://doi.org/10.1099/mic.0.26426-0

Utaida, S., Pfeltz, R. F., Jayaswal, R. K., & Wilkinson, B. J. (2006). Autolytic properties of glycopeptide - intermediate Staphylococcus aureus Mu50. Antimicrobial Agents and Chemotherapy, 50(4), 1541-1545. https://doi.org/10.1128/aac.50.4.1541-1545.2006

Vu, T. V. D., Choisy, M., Do, T. T. N., Nguyen, V. M. H., Campbell, J. I., Le, T. H., ... & VINARES consortium. (2021). Antimicrobial susceptibility testing results from 13 hospitals in Viet Nam: VINARES 2016-2017. Antimicrobial Resistance and Infection Control, 10, Article 78. https://doi.org/10.1186/s13756-021-00937-4

Xu, J., Pang, L., Ma, X. X., Hu, J., Tian, Y., Yang, Y. L., & Sun, D. D. (2018). Phenotype and molecular characterization of Staphylococcus aureus with reduced vancomycin susceptibility derivated in vitro. Open Medicine (Wars), 13(1), 475-486. https://doi.org/10.1515/med-2018-0071

Zhu, J., Liu, B., Shu, X., & Sun, B. (2021). A novel mutation of walK confers vancomycin-intermediate resistance in methicillin-susceptible Staphylococcus aureus. International Journal of Medical Microbiology, 311(2), Article151473. https://doi.org/10.1016/j.ijmm.2021.151473

Zhu, X., Liu, C., Gao, S., Lu, Y., Chen, Z., & Sun, Z. (2015). Vancomycin intermediate-resistant Staphylococcus aureus (VISA) isolated from a patient who never received vancomycin treatment. International Journal of Infectious Diseases, 33, 185-190. https://doi.org/10.1016/j.ijid.2014.12.038