RETRACTED ARTICLE: A leptospiral AAA+ chaperone–Ntn peptidase complex, HslUV, contributes to the intracellular survival of Leptospira interrogans in hosts and the transmission of leptospirosis
Authors: Shi-Lei Dong
Xu&#x27;ai Lin
Jie Yan
Yu-Mei Ge
Wei-Lin Hu
David M Ojcius
Journal: Emerging Microbes & Infections (2017)
Discipline: MICROBIOLOGY
Keywords: Leptospirosis; Leptospira; pathogenesis; transmission; HslUV
Affiliations: Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesZhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China, Department of Medical Microbiology and ParasitologyZhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China, Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated HospitalZhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China, Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang 310013, China, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang 310014, China, Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA 94103, USA

Abstract:  Leptospirosis caused by Leptospira is a zoonotic disease of global importance but it is considered as an emerging or re-emerging infectious disease in many areas in the world. Until now, the mechanisms about pathogenesis and transmission of Leptospira remains poorly understood. As eukaryotic and prokaryotic proteins can be denatured in adverse environments and chaperone-protease/peptidase complexes degrade these harmful proteins, we speculate that infection may also cause leptospiral protein denaturation, and the HslU and HslV proteins of L. interrogans may compose a complex to degrade denatured proteins that enhances leptospiral survival in hosts. Here we show that leptospiral HslUV is an ATP-dependent chaperone-peptidase complex containing ATPase associated with various cellular activity (AAA+) and N-terminal nucleophile (Ntn) hydrolase superfamily domains, respectively, which hydrolyzed casein and chymotrypsin-like substrates, and this hydrolysis was blocked by threonine protease inhibitors. The infection of J774A.1 macrophages caused the increase of leptospiral denatured protein aggresomes, but more aggresomes accumulated in hslUV gene-deleted mutant. The abundant denatured leptospiral proteins are involved in ribosomal structure, flagellar assembly, two-component signaling systems and transmembrane transport. Compared to the wild-type strain, infection of cells in vitro with the mutant resulted in a higher number of dead leptospires, less leptospiral colony-forming units and lower growth ability, but also displayed a lower half lethal dose, attenuated histopathological injury and decreased leptospiral loading in lungs, liver, kidneys, peripheral blood and urine in hamsters. Therefore, our findings confirmed that HslUV AAA+ chaperone-Ntn peptidase complex of L. interrogans contributes to leptospiral survival in hosts and transmission of leptospirosis. 

Retracted: Yes

PubPeer comments:
 Figure 7A. * Blue boxes: The Wild-type Kidney 3d panel (right) appears to show an overlap with the DeltaMP1 Kidney 7d panel (left) in Figure 5 of a 2020 paper by some of the same authors, i.e. Yu-Mei Ge et al. , DOI: 10.1093 infdis jiaa176 Could the authors check which of these two very different samples is the correct one, please? ![file] , 
 Figure 6A. Some panels appear to be showing the same bacterial cells. Leptospira that look similar to each other are highlighted in boxes of the same color. ![file] , 
 Figure 7E is one of three figures from three different papers from this research group that appear to share Leptospira cells. * Figure 6C from Yu-Mei Ge et al., Journal of Infectious Diseases (2020), DOI: 10.1093 infdis jiaa176, see: https: pubpeer.com publications 9AA7CE8CF0C2BB2FFA3EE46007EE29 * Figure 7E from Shi-Lei Dong et al., Emerging Microbes Infections (2017), DOI: 10.1038 emi.2017.93, see: https: pubpeer.com publications 8150A52142B1B0920EF68E9F1D8DD2 (this paper) * Figure 5D from Kokouvi Kassegne et al., Journal of Infectious Diseases (2014), DOI: 10.1093 infdis jit659, see: https: pubpeer.com publications 29E72E4707C8EDA9791586F41421B5 ![file] , 
 Figure 6A, update after posting this on social media, with a contribution by a Twitter user: ![file] , 
 We thank the readers for the comment. We are very sorry that the manuscript had these issues. I am contacting the other co-authors to check the data. We are repeating the experiment and will contact the journal for advice. , 
 April 22 2021 retraction, found here: https: www.tandfonline.com doi full 10.1080 22221751.2021.1917762  This article is being retracted due to reuse of images from other articles by the same authors, representing different results. (...) When approached for an explanation, the authors were unable to provide an explanation or verify their original data. The authors wish to apologize for their errors and the resulting inconvenience. The authors agree with the decision to retract this article. I thank the journal publisher staff and authors for their cooperation. , 
 2021 retraction. https: www.tandfonline.com doi full 10.1080 22221751.2021.1917762 We, the Editors and Publishers of Emerging Microbes and Infections, have retracted the following article: Shi-Lei Dong, Wei-Lin Hu, Yu-Mei Ge, David M Ojcius, Xu ai Lin Jie Yan (2017) A leptospiral AAA+ chaperoneu2013Ntn peptidase complex, HslUV, contributes to the intracellular survival of Leptospira interrogans in hosts and the transmission of leptospirosis, Emerging Microbes Infections, 6:1, 1-16, DOI: 10.1038 emi.2017.93 This article is being retracted due to reuse of images from other articles by the same authors, representing different results. This includes a histopathology panel from Figure 7A (Wild-type 3d Kidney), which can be found in the following article, where it is presented as Figure 5 (u0394MPI Kidney 7d), with slightly altered rotation and staining: Yu-Mei Ge, Ai-Hua Sun, David M Ojcius, Shi-Jun Li, Wei-Lin Hu, Xuu2019ai Lin, Jie Yan, M16-Type Metallopeptidases Are Involved in Virulence for Invasiveness and Diffusion of Leptospira interrogans and Transmission of Leptospirosis, The Journal of Infectious Diseases, Volume 222, Issue 6, 15 September 2020, Pages 1008u20131020, DOI: 10.1093 infdis jiaa176 In addition, a Leptospira cell staining panel from Figure 7E (7 d u0394hsIUB) was found to have been presented as a result from an earlier experiment, within urine of a different strain of hamsters, within Figure 5D (7(100x) Wild-type strain) of the following article: Kokouvi Kassegne, Weilin Hu, David M. Ojcius, Dexter Sun, Yumei Ge, Jinfang Zhao, X. Frank Yang, Lanjuan Li, Jie Yan, Identification of Collagenase as a Critical Virulence Factor for Invasiveness and Transmission of Pathogenic Leptospira Species, The Journal of Infectious Diseases, Volume 209, Issue 7, 1 April 2014, Pages 1105u20131115, DOI: 10.1093 infdis jit659 When approached for an explanation, the authors were unable to provide an explanation or verify their original data. The authors wish to apologize for their errors and the resulting inconvenience. The authors agree with the decision to retract this article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,