Genomic and Phenotypic Evolution of Tigecycline-Resistant Acinetobacter baumannii in Critically Ill Patients.

Acinetobacter baumannii is an important opportunistic pathogen of nosocomial infections. A. baumannii presently exhibits increasing antibiotic resistance, which poses great challenges to public health. The occurrence of tigecycline-resistant A. baumannii is related to tigecycline treatment and the within-host evolution of bacteria. We analyzed isogenic A. baumannii isolates from two critically ill patients who underwent tigecycline treatment. Whole-genome sequencing and comparative analyses were performed to determine the characteristics of genomic evolution. We conducted phenotypic studies, including in vitro antibiotic sensitivity tests, biofilm formation tests, growth curve determination, serum bactericidal determination, and Galleria mellonella lethality assays. In vivo emergent tigecycline resistance was observed after tigecycline treatment. After the withdrawal of tigecycline pressure, tigecycline-resistant isolates were not isolated from one patient. Four tigecycline-resistant isolates exhibited lower growth rates. The biofilm formation and virulence characteristics of tigecycline-resistant isolates were reasonably different between the two patients. A special phenotype appeared after tigecycline treatment in both patients, accompanied by reduced serum tolerance, enhanced biofilm formation ability, and reduced virulence of Galleria mellonella. Most of the genomic variation occurred after the tigecycline treatment, primarily involving transcription-, signal transduction-, translation-, ribosomal biogenesis-, and cell wall biogenesis-related genes. We determined that the genomic variations in baeR, wzc, aroQ, rluC, and adeS and acquisition of ISAba1 were associated with tigecycline resistance in vivo. Capsular polysaccharide-related genes, wzc, and itrA2, and aroQ, were the key genes related to the virulence evolution of A. baumannii within the host. IMPORTANCE Multidrug-resistant Acinetobacter baumannii poses a huge challenge to clinical treatment, and tigecycline is considered a last-line drug for the treatment of multidrug-resistant A. baumannii. However, the mechanism of tigecycline resistance in vivo has not been elucidated. This study analyzed the genomic and phenotypic evolution of tigecycline-resistant A. baumannii in two critically ill patients. In this study, after treatment with tigecycline, tigecycline-resistant A. baumannii emerged with higher fitness costs. After the withdrawal of tigecycline pressure, tigecycline-resistant isolates were not isolated from one patient. The in vivo and in vitro virulence of the isolates exhibited diametrically opposite results in the two patients. Genomic variations in baeR, wzc, aroQ, rluC, and adeS and acquisition of ISAba1 were associated with tigecycline resistance in vivo. The capsular polysaccharide-related genes, wzc, itrA2, and aroQ, were the key genes related to the virulence of A. baumannii in hosts. Our research provides a theoretical basis for elucidating the mechanism of tigecycline resistance and presents new clues for future surveillance and treatment of multidrug-resistant A. baumannii.

[Visualization analysis of traditional Chinese medicine for neurogenesis research based on CiteSpace].

To analyze the research hotspots and trends of traditional Chinese medicine(TCM) for neurogenesis with use of CiteSpace 5.7.R3 software. The bibliometrics analysis on the literatures of TCM for neurogenesis from 1987 to 2020 included in the CNKI database was conducted to visualize the number of papers, authors, institutions and keywords. Totally 736 literatures were included and the volume of annual publications showed an upward in volatility. At present, several stable research teams have been formed, which were represented by DING Fei, ZHOU Chong-jian and ZHOU Yong-hong, but the cooperation was not close among the teams. According to the analysis of research institutions, Institute of Diagnostics of Hunan University of Chinese Medicine and Acupuncture Research Center of Tianjin University of Traditional Chinese Medicine produced largest number of literatures. The cooperation among institutions, with universities of TCM and affiliated hospitals as the main research force, was characterized by dominant cooperation among regional institutions and less cross-regional cooperation. Keywords analysis showed that in the field of TCM for neurogenesis, a lot of studies mainly focused on the disease field, treatment and medication, TCM therapy and molecular mechanism. The research on TCM therapy and molecular mechanism for neurogenesis of central nervous system will be the research hotspots in future.