scholarly journals In vitro Activity and Heteroresistance of Omadacycline Against Clinical Staphylococcus aureus Isolates From China Reveal the Impact of Omadacycline Susceptibility by Branched-Chain Amino Acid Transport System II Carrier Protein, Na/Pi Cotransporter Family Protein, and Fibronectin-Binding Protein

2019 ◽  
Vol 10 ◽  
Author(s):  
Bing Bai ◽  
Zhiwei Lin ◽  
Zhangya Pu ◽  
Guangjian Xu ◽  
Fan Zhang ◽  
...  
2020 ◽  
Author(s):  
Zhanwen Wang ◽  
Zhiwei Lin ◽  
Bing Bai ◽  
Guangjian Xu ◽  
Peiyu Li ◽  
...  

Abstract Objectives: 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 Erava resistance and heteroresistance in S. aureus.Methods: 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.


2020 ◽  
Vol 15 (10) ◽  
pp. 855-868 ◽  
Author(s):  
Hua Zha ◽  
Yanfei Chen ◽  
Jieyun Wu ◽  
Kevin Chang ◽  
Yanmeng Lu ◽  
...  

Aim: Investigation of characteristics of different duodenal microbial colonization states in patients with liver cirrhosis (LC). Materials & methods: Deep-sequencing analyses of the 16S rRNA gene V1-V3 regions were performed. Results: Both bacterial compositions and richness were different between the three-clustered LC microbiotas, in other words, Cluster_1_LC, Cluster_2_LC and Cluster_3_LC. Cluster_1_LC were more likely at severe dysbiosis status due to its lowest modified cirrhosis dysbiosis ratio. OTU12_ Prevotella and OTU10_ Comamonas were most associated with Cluster_1_LC and Cluster_3_LC, respectively, while OTU38_ Alloprevotella was vital in Cluster_2_LC. Pyruvate-ferredoxin/flavodoxin oxidoreductase, dihydroorotate dehydrogenase and branched-chain amino acid transport system substrate-binding protein were most associated with Cluster_1_LC, Cluster_2_LC and Cluster_3_LC, respectively. Conclusion: The three duodenal microbial colonization states had distinct representative characteristics, which might reflect the health status of cirrhotic patients.


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