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Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus.
BMC Microbiol. 2020 Jul 01; 20(1):189.BM

Abstract

BACKGROUND

Our previous research indicated the excellent in vitro antibacterial activity of Eravacycline (Erava) and its heteroresistance frequency against clinical Staphylococcus aureus isolates. In this study, we further aimed to investigate the mechanisms of Erava resistance and heteroresistance in S. aureus. Eight parental S. aureus isolates were induced under Erava pressure in vitro and the Erava-resistant isolates were selected and identified. Then, the genetic mutations of 30S ribosomal subunits were analyzed by PCR and sequence alignment. RT-qPCR analysis were performed to compare the relative expression of eight candidate genes impacting the susceptibility of tetracycline (Tet) between the resistant or heteroresistant and parental isolates. Furthermore, the in vitro overexpression vectors of three selected candidate genes were constructed to test their impact on the heteroresistance and resistance of Erava in S. aureus.

RESULTS

The MICs elevation in Erava-induced resistant S. aureus isolates were identified and the increasing MICs values of another two Tet class antibiotics, including both omadacycline (Omada) and tigecycline (Tige) were also tested. Genetic mutations in 30S ribosomal protein S10 were found frequently in Erava-derived resistant isolates. RT-qPCR analysis and the in vitro overexpression experiments indicated that USA300HOU_RS00550 (an Na/Pi cotransporter family protein) and USA300HOU_RS01625 (a branched-chain amino acid transport system II carrier protein) contributed to Erava heteroresistance in S. aureus.

CONCLUSION

Genetic mutation of 30S ribosome subunits contributed to Erava resistance, and the transcriptional overexpression of USA300HOU_RS01625 and USA300HOU_RS00550 also participated in the occurrence of Erava heteroresistance in S. aureus.

Authors+Show Affiliations

Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. Quality control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital of Guangdong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. Quality control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital of Guangdong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. Quality control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital of Guangdong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. 16111010064@fudan.edu.cn. Quality control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital of Guangdong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. 16111010064@fudan.edu.cn.Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, Shenzhen Nanshan people's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. jinxinzheng@fudan.edu.cn. Quality control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital of Guangdong Medical University, No 89, Taoyuan Road, Nanshan district, Shenzhen, 518052, China. jinxinzheng@fudan.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32611319

Citation

Wang, Zhanwen, et al. "Eravacycline Susceptibility Was Impacted By Genetic Mutation of 30S Ribosome Subunits, and Branched-chain Amino Acid Transport System II Carrier Protein, Na/Pi Cotransporter Family Protein in Staphylococcus Aureus." BMC Microbiology, vol. 20, no. 1, 2020, p. 189.
Wang Z, Lin Z, Bai B, et al. Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus. BMC Microbiol. 2020;20(1):189.
Wang, Z., Lin, Z., Bai, B., Xu, G., Li, P., Yu, Z., Deng, Q., Shang, Y., & Zheng, J. (2020). Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus. BMC Microbiology, 20(1), 189. https://doi.org/10.1186/s12866-020-01869-6
Wang Z, et al. Eravacycline Susceptibility Was Impacted By Genetic Mutation of 30S Ribosome Subunits, and Branched-chain Amino Acid Transport System II Carrier Protein, Na/Pi Cotransporter Family Protein in Staphylococcus Aureus. BMC Microbiol. 2020 Jul 1;20(1):189. PubMed PMID: 32611319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus. AU - Wang,Zhanwen, AU - Lin,Zhiwei, AU - Bai,Bing, AU - Xu,Guangjian, AU - Li,Peiyu, AU - Yu,Zhijian, AU - Deng,Qiwen, AU - Shang,Yongpeng, AU - Zheng,Jinxin, Y1 - 2020/07/01/ PY - 2020/03/10/received PY - 2020/06/22/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - Antimicrobial activity KW - Antimicrobial agent KW - Eravacycline KW - Staphylococcus aureus SP - 189 EP - 189 JF - BMC microbiology JO - BMC Microbiol. VL - 20 IS - 1 N2 - BACKGROUND: Our previous research indicated the excellent in vitro antibacterial activity of Eravacycline (Erava) and its heteroresistance frequency against clinical Staphylococcus aureus isolates. In this study, we further aimed to investigate the mechanisms of Erava resistance and heteroresistance in S. aureus. Eight parental S. aureus isolates were induced under Erava pressure in vitro and the Erava-resistant isolates were selected and identified. Then, the genetic mutations of 30S ribosomal subunits were analyzed by PCR and sequence alignment. RT-qPCR analysis were performed to compare the relative expression of eight candidate genes impacting the susceptibility of tetracycline (Tet) between the resistant or heteroresistant and parental isolates. Furthermore, the in vitro overexpression vectors of three selected candidate genes were constructed to test their impact on the heteroresistance and resistance of Erava in S. aureus. RESULTS: The MICs elevation in Erava-induced resistant S. aureus isolates were identified and the increasing MICs values of another two Tet class antibiotics, including both omadacycline (Omada) and tigecycline (Tige) were also tested. Genetic mutations in 30S ribosomal protein S10 were found frequently in Erava-derived resistant isolates. RT-qPCR analysis and the in vitro overexpression experiments indicated that USA300HOU_RS00550 (an Na/Pi cotransporter family protein) and USA300HOU_RS01625 (a branched-chain amino acid transport system II carrier protein) contributed to Erava heteroresistance in S. aureus. CONCLUSION: Genetic mutation of 30S ribosome subunits contributed to Erava resistance, and the transcriptional overexpression of USA300HOU_RS01625 and USA300HOU_RS00550 also participated in the occurrence of Erava heteroresistance in S. aureus. SN - 1471-2180 UR - https://www.unboundmedicine.com/medline/citation/32611319/Eravacycline_susceptibility_was_impacted_by_genetic_mutation_of_30S_ribosome_subunits,_and_branched-chain_amino_acid_transport_system_II_carrier_protein,_Na/Pi_cotransporter_family_protein_in_Staphylococcus_aureus L2 - https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-020-01869-6 DB - PRIME DP - Unbound Medicine ER -
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