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194 results on '"Chu, Haiqing"'

1. Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection

Author

Bing, Jian, Guan, Zhangyue, Zheng, Tianhong, Ennis, Craig L, Nobile, Clarissa J, Chen, Changbin, Chu, Haiqing, and Huang, Guanghua

Subjects
Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Infectious Diseases, Genetics, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Mice, Candida, Candidiasis, Candida auris, Saccharomyces cerevisiae, Phenotype, Sepsis, Antifungal Agents, Microbial Sensitivity Tests, Mammals
Abstract

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.

Published
2024

10. Impaired ESX‐3 Induces Bedaquiline Persistence in Mycobacterium abscessus Growing Under Iron‐Limited Conditions.

Author

Li, Bing, He, Siyuan, Tan, Zhili, Li, Anqi, Fan, Junsheng, Zhao, Lan, Zhang, Zhemin, and Chu, Haiqing

Abstract

ESX‐3 is a secretion pathway which is essential for mycobactin‐mediated iron acquisition under iron‐limited conditions. Although present in all Mycobacterium sp., ESX‐3 remains to be elucidated in Mycobacterium abscessus. In the study reported here, impaired ESX‐3 seriously restricts the growth of M. abscesses under iron‐limited conditions; growth is salvaged by functional ESX‐3 or iron supplementation. Notably, impaired ESX‐3 does not kill M. abscesses when environmental iron is insufficient but induces persistence to bedaquiline, a diarylquinoline class antibiotic used to treat multidrug‐resistant mycobacteria. One potential mechanism contributing to persistence is the iron deficiency due to impaired ESX‐3 suppressing succinate dehydrogenase activity, which dysregulates the tricarboxylic acid cycle and inactivates bedaquiline. Experiments conducted here also demonstrate that the regulator, MtrA, can bind ESX‐3 and promote the survival of M. abscessus. As such, this study suggests that a novel pathway involving MtrA, ESX‐3, iron metabolism, and the TCA cycle contributes to bedaquiline persistence in M. abscesses growing under iron‐limited conditions. [ABSTRACT FROM AUTHOR]

Published
2023
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12. sRNA21, a novel small RNA, protects Mycobacterium abscessus against oxidative stress.

Author

Tan, Zhili, Fan, Junsheng, He, Siyuan, Zhang, Zhemin, and Chu, Haiqing

Abstract

Background: During infection, Mycobacterium abscessus encounters numerous environmental changes and adapts to them using a variety of complex mechanisms. Non‐coding small RNAs (sRNAs) have been shown in other bacteria to be involved in post‐transcriptional regulatory pathways, including environmental stress adaptation. However, the potential role of sRNAs in the resistance to oxidative stress in M. abscessus was not clearly described. Methods: In the present study, we analyzed putative sRNAs identified by RNA‐sequencing (RNA‐seq) experiments in M. abscessus ATCC_19977 under oxidative stress, and the transcription profiles of sRNAs with differential expression were verified by quantitative reverse transcription‐PCR (qRT‐PCR). Six sRNA overexpression strains were constructed, and the differences in growth curves between these strains and the control strain were verified. An upregulated sRNA under oxidative stress was selected and named sRNA21. The survival ability of the sRNA21 overexpression strain was assessed, and computer‐based approaches were used to predict the targets and pathways regulated by sRNA21. The total ATP production and NAD+/NADH ratio of the sRNA21 overexpression strain were measured. The expression level of antioxidase‐related genes and the activity of antioxidase were tested to confirm the interaction of sRNA21 with the predicted target genes in silico. Results: In total, 14 putative sRNAs were identified under oxidative stress, and the qRT‐PCR analysis of six sRNAs showed comparable results to RNA‐seq assays. Overexpression of sRNA21 in M. abscessus increased cell growth rate and intracellular ATP level before and after peroxide exposure. The expression of genes encoding alkyl hydroperoxidase and superoxide dismutase was significantly increased, and superoxide dismutase activity was enhanced in the sRNA21 overexpression strain. Meanwhile, after sRNA21 overexpression, the intracellular NAD+/NADH ratio decreased, indicating changes in redox homeostasis. Conclusions: Our findings show that sRNA21 is an oxidative stress‐induced sRNA that increases M. abscessus survival and promotes the expression of antioxidant enzymes under oxidative stress. These findings may provide new insights into the adaptive transcriptional response of M. abscessus to oxidative stress. [ABSTRACT FROM AUTHOR]

Published
2023
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25. In vitro activity of rifabutin against Mycobacterium abscessus, clinical isolates.

Author

Chen, Jianhui, Zhang, Haonan, Guo, Qi, He, Siyuan, Xu, Liyun, Zhang, Zhemin, Ma, Jian, and Chu, Haiqing

Subjects
AMIKACIN, MYCOBACTERIUM, WHOLE genome sequencing, MYCOBACTERIA
Abstract

The antibiotic options available for Mycobacterium abscessus (M. abscessus) infection are limited and no definitive therapeutic strategies have been formulated. The recent discovery that rifabutin is active against M. abscessus has raised interest in using rifabutin to treat this intractable disease. In this study, we evaluated the in vitro activity of rifabutin against 194 M. abscessus clinical isolates collected during 2012 January to 2017 December. As expected, rifabutin demonstrated considerably lower MICs against M. abscessus, with an MIC50 of 2 μg/mL and MIC90 of 4 μg/mL, respectively. Notably, the anti‐M.abscessus activity was even stronger among clarithromycin‐insusceptible strains. In addition, M. abscessus isolates with a rough morphotype were more sensitive to rifabutin compared with those forming smooth colonies when considered as a whole or in separate subspecies. Results from synergistic experiments revealed that the in vitro activity of rifabutin was significantly enhanced by the addition of amikacin, suggesting a promising strategy for M. abscessus infection combination treatment. Finally, five and three mutation patterns in rpoB and arr, respectively, were identified among the 194 strains through whole genome sequencing. However, none of them conferred rifabutin resistance. Our study is among the first to report the susceptibility of M. abscessus to rifabutin in vitro with a large amount of clinical isolates, suggesting that rifabutin is active, both alone and in combination, against M. abscessus and is worth considering as part of a combination treatment regimen for M. abscessus infections. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Zinc Chelator N,N,N′,N′-Tetrakis(2-Pyridylmethyl)Ethylenediamine Reduces the Resistance of Mycobacterium abscessus to Imipenem

Author

He,Siyuan, Zou,Yuzhen, Zhan,Mengling, Guo,Qi, Zhang,Yongjie, Zhang,Zhemin, Li,Bing, Zhang,Shaoyan, and Chu,Haiqing

Subjects
Infection and Drug Resistance, polycyclic compounds, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Siyuan He,1,2,* Yuzhen Zou,1,2,* Mengling Zhan,1,2,* Qi Guo,1,2 Yongjie Zhang,1,2 Zhemin Zhang,1 Bing Li,1 Shaoyan Zhang,1 Haiqing Chu1,3 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 2Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 3Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiqing Chu; Shaoyan ZhangDepartment of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel/ Fax +86 21 6511 5006Email chu_haiqing@126.com; zhangshaoyan000@163.comPurpose: Imipenem is one of the very few effective options for treating Mycobacterium abscessus (M. abscessus) infections; the development of imipenem resistance is a major health concern.Materials and Methods: The susceptibility of 194 clinical M. abscessus isolates to imipenem was determined. The ability of imipenem to synergize with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a zinc chelator and a metallo-β-lactamases (MBLs) inhibitor, to inhibit M. abscessus growth was also assessed.Results: M. abscessus exhibited an elevated resistance to imipenem (MIC50 = 16 mg/L, MIC90 = 64 mg/L). A combination of TPEN and imipenem synergized to inhibit the growth of 100% of imipenem-resistant and 79.2% of imipenem-resistance intermediate isolates; no synergy was observed treating imipenem-sensitive isolates. A remarkable decrease in the MIC50 (from 16 to 4 mg/L) and MIC90 (from 64 to 8 mg/L) of imipenem was observed when it was combined with TPEN; the portion of imipenem-resistant isolates also decreased (from 48.4% to 0%). Consistent with these results demonstrating synergy, a time-kill assay showed the addition of TPEN significantly improved the bactericidal activity of imipenem toward M. abscessus. Similarly, EDTA (a potent MBLs inhibitor) promoted the anti-M. abscessus activity of imipenem in a disk assay, corroborating the effect of TPEN and supporting the role of MBLs in imipenem resistance exhibited by some isolates.Conclusion: These findings demonstrate that TPEN can reduce the resistance of M. abscessus to imipenem and suggest that the inhibition of MBLs activity is the underlying mechanism.Keywords: Mycobacterium abscessus, TPEN, imipenem resistance, metallo-β-lactamases

Published
2020

27. Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, Mycobacterium abscessus Isolates

Author

Guo, Qi, Chen, Jianhui, Zhang, Shaoyan, Zou, Yuzhen, Zhang, Yongjie, Huang, Dongdong, Zhang, Zhemin, Li, Bing, and Chu, Haiqing

Subjects
Mycobacterium abscessus, Infection and Drug Resistance, efflux pumps, clarithromycin resistance, bacterial infections and mycoses, Original Research
Abstract

Qi Guo,1,2 Jianhui Chen,1,2 Shaoyan Zhang,1 Yuzhen Zou,1,2 Yongjie Zhang,1,2 Dongdong Huang,1 Zhemin Zhang,1 Bing Li,1 Haiqing Chu1,3 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 2Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 3Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of ChinaCorrespondence: Haiqing Chu; Bing LiDepartment of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel/Fax +86 021 6511 5006Email chu_haiqing@126.com; libing044162@163.comPurpose: The emergence of clarithromycin resistance is a challenge in treating Mycobacterium abscessus infections. Known mechanisms that contribute to intrinsic clarithromycin resistance focus on rrl gene-related mutations, but resistant clinical isolates often exhibit an inconsistent rrl genotype.Patients and Methods: In this study, 194 clinical Mycobacterium abscessus isolates were collected from patients with lung infections and the whole genome of each isolate was sequenced. A comprehensive examination of the molecular mechanisms underlying intrinsic clarithromycin resistance was performed, combining MIC determination, comparative genome sequence analysis and qRT-PCR.Results: Of the 194 isolates, 13 (6.7%) were clarithromycin resistant; only seven of these harbored a rrl 2270/2271 mutation. The remaining six resistant isolates did not exhibit a specific resistance-associated mutation in the clarithromycin target-site genes, rrl, rplC, rplD and rplV, or in the rrl modification gene erm(41). qRT-PCR analysis showed that the increased expression of the efflux pump genes, MAB_2355c, MAB_1409c and MAB_1846, as well as their positive regulatory gene whiB7, consistently correlated with increased clarithromycin resistance. The presence of efflux pump inhibitors significantly decreased the MIC of clarithromycin for nonsusceptible isolates, especially the intrinsic resistant isolates that exhibited no rrl 2270/2271 mutation.Conclusion: These findings indicate that efflux pumps play a prominent role in the intrinsic resistance of M. abscessus to clarithromycin, complementing other known resistance mechanisms.Keywords: Mycobacterium abscessus, clarithromycin resistance, efflux pumps

Published
2020

28. Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, Mycobacterium abscessus Isolates

Author

Guo,Qi, Chen,Jianhui, Zhang,Shaoyan, Zou,Yuzhen, Zhang,Yongjie, Huang,Dongdong, Zhang,Zhemin, Li,Bing, Chu,Haiqing, Guo,Qi, Chen,Jianhui, Zhang,Shaoyan, Zou,Yuzhen, Zhang,Yongjie, Huang,Dongdong, Zhang,Zhemin, Li,Bing, and Chu,Haiqing

Abstract

Qi Guo,1,2 Jianhui Chen,1,2 Shaoyan Zhang,1 Yuzhen Zou,1,2 Yongjie Zhang,1,2 Dongdong Huang,1 Zhemin Zhang,1 Bing Li,1 Haiqing Chu1,3 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 2Tongji University School of Medicine, Shanghai 200092, People’s Republic of China; 3Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of ChinaCorrespondence: Haiqing Chu; Bing LiDepartment of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel/Fax +86 021 6511 5006Email chu_haiqing@126.com; libing044162@163.comPurpose: The emergence of clarithromycin resistance is a challenge in treating Mycobacterium abscessus infections. Known mechanisms that contribute to intrinsic clarithromycin resistance focus on rrl gene-related mutations, but resistant clinical isolates often exhibit an inconsistent rrl genotype.Patients and Methods: In this study, 194 clinical Mycobacterium abscessus isolates were collected from patients with lung infections and the whole genome of each isolate was sequenced. A comprehensive examination of the molecular mechanisms underlying intrinsic clarithromycin resistance was performed, combining MIC determination, comparative genome sequence analysis and qRT-PCR.Results: Of the 194 isolates, 13 (6.7%) were clarithromycin resistant; only seven of these harbored a rrl 2270/2271 mutation. The remaining six resistant isolates did not exhibit a specific resistance-associated mutation in the clarithromycin target-site genes, rrl, rplC, rplD and rplV, or in the rrl modification gene erm(41). qRT-PCR analysis showed that the increased expression of the efflux pump genes, MAB_2355c, MAB_1409c and MAB_1846, as well as their positive regulatory gen

Published
2020

38. Prevalence of nontuberculous mycobacteria in patients with bronchiectasis: a meta-analysis

Author

Chu, Haiqing, Zhao, Lan, Xiao, Heping, Zhang, Zhemin, Zhang, Jinbo, Gui, Tao, Gong, Sugang, Xu, Liyun, and Sun, Xiwen

Subjects
nontuberculous mycobacteria, meta-analysis, Systematic review/Meta-analysis, bronchiectasis, prevalence, bacterial infections and mycoses
Abstract

Introduction Nontuberculous mycobacteria (NTM) have emerged as critical opportunistic pathogens of lung diseases recently. Patients with preexisting bronchiectasis are susceptible to NTM. Nevertheless, patients with preexisting bronchiectasis are susceptible to NTM but the prevalence of NTM pulmonary infection in different species and geographical areas is still not fully understood. Material and methods The relevant data of the prevalence of NTM in patients with bronchiectasis were retrieved by searching the main databases such as PubMed, MEDLINE, Cochrane Library, and EMBASE. This meta-analysis was performed using Rev. Man 5.1 and Stata 11.0 software. The collected information of NTM prevalence was chosen as the effect size. Results The results of the meta-analysis showed that the overall prevalence of NTM was 9.3% in patients with bronchiectasis. The further stratification of subgroup analysis indicated that the combined prevalence of NTM was higher in studies whose “sample size” was more than or equal to 100 (p = 0.002), in studies in which “time of study” was after or equal to 2002 (p < 0.001), in studies in which “participants’ geographic location” was Asian (p < 0.001) and in studies whose “method of study” was retrospective (p = 0.002) as well, compared with corresponding groups. Conclusions Our findings suggested that the prevalence NTM infection is high in patients with bronchiectasis. A larger number of definitive randomized trials are still required to assess this research issue.

Published
2014

44. Clinical characteristics of amyloidosis with isolated respiratory system involvement: a review of 13 cases

Author

Chu, Haiqing, Zhao, Lan, Zhang, Zhemin, Gui, Tao, Yi, Xianghua, and Sun, Xiwen

Subjects
Lung diseases -- Care and treatment -- Patient outcomes -- Demographic aspects -- Research, Amyloidosis -- Care and treatment -- Patient outcomes -- Demographic aspects -- Research, Health
Abstract

Byline: Haiqing. Chu, Lan. Zhao, Zhemin. Zhang, Tao. Gui, Xianghua. Yi, Xiwen. Sun Background: Isolated pulmonary amyloidosis is a very rare disease. Methods: We retrospectively reviewed the records of patients [...]

Published
2012

45. Characterization of Mycobacterium Abscessus Subtypes in Shanghai of China

Author

Luo, Liulin, Li, Bing, Chu, Haiqing, Huang, Dongdong, Zhang, Zhemin, Zhang, Jingbo, Gui, Tao, Xu, Liyun, Zhao, Lan, Sun, Xiwen, and Xiao, Heping

Subjects
Male, China, Mycobacterium Infections, Nontuberculous, Nontuberculous Mycobacteria, Clinical Trial/Experimental Study, Microbial Sensitivity Tests, Middle Aged, bacterial infections and mycoses, Anti-Bacterial Agents, Bacterial Typing Techniques, Electrophoresis, Gel, Pulsed-Field, Pneumonia, Bacterial, DNA Barcoding, Taxonomic, Humans, Female, Tomography, X-Ray Computed, Research Article, Multilocus Sequence Typing, Retrospective Studies
Abstract

The aim of the study was to investigate the epidemic characteristics of Mycobacterium abscessus in Shanghai. Fifty-five strains from 55 M. abscessus pulmonary disease patients were isolated. Drug sensitivity was measured by a broth microdilution method. Subtypes of M. abscessus were identified by DNA sequencing. Multilocus sequence typing (MLST), mining spanning tree (MST), and pulsed-field gel electrophoresis (PFGE) were used to analyze sequence types (ST) and clonal complexes (CC). Clinical manifestations were assessed by CT imaging. We identified 42 A isolates, 11 M, and 2 B-subtypes. A and M were highly sensitive to tigecycline and amikacin (97.6–100%). The A-type easily developed drug resistance against clarithromycin. Both types were highly resistance to sulfonamides, moxifloxacin, doxycycline, imipenem, and tobramycin. MLST analysis identified 41 STs including 32 new STs. The MST algorithm distributed 55 isolates into 12 separate CC. The PFGE analysis exhibited 53 distinct restriction patterns and the M-type was closely clustered according to their ST and CC numbers. CT imaging showed that tree-in-bud and patch shadow were commonly observed in M-type, whereas pulmonary cavities were often found in A-type infection patients (P

Published
2016

49. Evaluation of Matrix-Assisted Laser Desorption Ionization−Time of Flight Mass Spectrometry for Identification of Mycobacterium abscessus Subspecies According to Whole-Genome Sequencing

Author

Luo, Liulin, primary, Liu, Weijia, additional, Li, Bing, additional, Li, Mengling, additional, Huang, Dongdong, additional, Jing, Linjie, additional, Chen, Huiping, additional, Yang, Jinghui, additional, Yue, Jun, additional, Wang, Fang, additional, Chu, Haiqing, additional, and Zhang, Zhemin, additional

Published
2016
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50. Detection and molecular characterisation of amikacin-resistant Mycobacterium abscessusisolated from patients with pulmonary disease

Author

Wu, Mingyan, Li, Bing, Guo, Qi, Xu, Liyun, Zou, Yuzhen, Zhang, Yongjie, Zhan, Mengling, Xu, Benyong, Ye, Meiping, Yu, Fangyou, Zhang, Zhemin, and Chu, Haiqing

Abstract

•Amikacin (AMK) resistance in clinical Mycobacterium abscessushas emerged.•Data on the prevalence of AMK resistance and underlying resistance mechanisms in clinical M. abscessusare limited.•AMK had high in vitro killing activity against M. abscessusfrom lung infections, with a resistance rate of 2.6% (5/194).•Most of the AMK-resistant isolates harboured a target site rrsmutation.•A1408G mutation in rrsand overexpression of WhiB7 and Tap are main mechanisms of AMK resistance in clinical M. abscessus.

Published
2019
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