The mammalian cell entry (Mce) protein of pathogenic Leptospira species is responsible for RGD motif-dependent infection of cells and animals
Authors: Xuai Lin
Liwei Li
Chenglin Zhang
Dexter Sun
Jie Yan
Lanjuan Li
David M Ojcius
Lei Zhang
Jinfang Zhao
Journal: Molecular Microbiology (2012)
Discipline: MICROBIOLOGY
Keywords: Mammalian cell entry proteins; Mycobacterium tuberculosis; Leptospira interrogans; virulence; gene expression
Affiliations: Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract:  Mammalian cell entry proteins (Mces) contribute to Mycobacterium tuberculosis virulence. A mce homologue has been identified in the Leptospira interrogans genome, but its function was unknown. We showed that the mce gene is expressed only by pathogenic Leptospira strains tested. Leptospiral mce mRNA and Mce protein levels increased during infection of macrophages. The ability to infect macrophages was significantly lower in a strain with the mce gene deleted (mce(-) ). Complementation of the mce gene restored the ability of the mutant strain (mce(com) ) to adhere to and invade cells. Importantly, the mce gene knock-in strain (mce(+) ) derived from L. biflexa acquired the ability to infect cells, and the mce(+/ΔRAA) knock-in strain (in which the RGD motif was replaced by RAA) was unable to infect cells. The mce(-) mutant was also dramatically less efficient in infecting hamsters than the wild-type L. interrogans strain, and fewer leptospires of the mutant were found in peripheral blood monocytes and the urine from infected animals. The recombinant Mce protein showed a high binding affinity to the integrins α5β1 and α(V) β3. Blockade of the two integrins or the Mce protein decreased leptospiral adherence and invasiveness. The results showed that Mce is an RGD-motif-dependent virulence factor in pathogenic Leptospira species. 

Retracted: No

PubPeer comments:
 Could the authors comment on the relevance of these References?  Therefore, due to the good biocompatibility of the complex materials, many literatures have studied [transmission-metal coordination chemistry] [6u20138]. - [6] Zhang, D.; Wang, M. M.; Jiang, N.; Liu, Y.; Yu, X. N.; Zhang, H. B. **Electrochemical Corrosion Behavior of Ni-Doped ZnO Thin Film Coated on Low Carbon Steel Substrate in 3.5% NaCl Solution**. Int. J. Electrochem. Sci. 2020, 15, 4117u20134126. - [7]. Su, J.; Sheng, Z.; Xie, L.; Li, G.; Liu, A. X. **Fast Splitting Based Tag Identification Algorithm for anti-Collision in UHF RFID System**. IEEE Trans. Commun. 2019, 67, 2527u20132538. DOI: 10.1109 TCOMM.2018.2884001. - [8]. Arshad, M.; Du, H. L.; Javed, M. S.; Maqsood, A.; Ashraf, I.; Hussain, S.; Ma, W. L.; Ran, H. P. Fabrication, Structure, and Frequency-Dependent Electrical and Dielectric Properties of **Sr-Doped BaTiO3 Ceramics**. Ceram. Int. 2020, 46, 2238u20132246. DOI: 10.1016 j.ceramint.2019.09.208.  For instance, Raja and others synthesized the cobalt(II) isoniazid coordination polymer which has the anticancer activity [9]. - [9]. Du, H.; Ma, C.; Ma, W.; Wang, H. Microstructure Evolution and Dielectric Properties of **Ce-Doped SrBi4Ti4O15 Ceramics** Synthesized via Glycine-Nitrate Process. PAC 2018, 12, 303u2013312. DOI: 10.2298 PAC1804303D. , 
 Fig 2  (c) 1u2019s EDS analysis for the surface (up) and the interior (down, after a single crystal is cut) of a crystal sample for 1. (d) The SEM image of nano 1. ![file] Fig 2c from [Guo et al (2020)] : ![file] , 
 Fig 5,  Inhibited Bcl-2 protein expression in cancer cells after nano 1 treatment . Are two panels supposed to be duplicates? ![file] , 
 Mustn t forget the title:  anti-breast cancer activity on **osteogenic sarcoma** . Osteogenic sarcoma is not mentioned again. Reviewers and editors didn t care. Perhaps the actual authors were not certain of the customer for the manuscript when they started assembling it. , 
 Another interesting aspect of the References is the chunk of citations to the work of Kirillov and Kirillova.  Hence, this compound extends the family of heterometallic coordination polymers possessing a diversity of functional properties and applications [14u201318]. - [15] **Kirillov, A. M.**; Karabach, Y. Y.; Kirillova, M. V.; Haukka, M.; Pombeiro, A. J. L. Topologically Unique 2D Heterometallic Cu(II) Mg Coordination Polymer: Synthesis, Structural Features, and Catalytic Use in Alkane Hydrocarboxylation. Cryst. Growth Des. 2012, 12, 1069u20131074. DOI: 10.1021 cg201459k. - [16] Kirillova, M. V.; **Kirillov, A. M.**; Martins, A. N. C.; Graiff, C.; Tiripicchio, A.; Pombeiro, A. J. L. Topologically Unique Heterometallic Cu(II) Li Coordination Polymers Self-Assembled from N,N-Bis(2-Hydroxyethyl)-2-Aminoethanesulfonic Acid Biobuffer: Versatile Catalyst Precursors for Mild Hydrocarboxylation of Alkanes to Carboxylic Acids. Inorg. Chem. 2012, 51, 5224u20135234. DOI: 10.1021 ic300123d. - [17] **Kirillov, A. M.**; Coelho, J. A. S.; Kirillova, M. V.; da Silva, M. F. C. G.; Nesterov, D. S.; Gruenwald, K. R.; Haukka, M.; Pombeiro, A. J. L. Bringing an u201cOldu201d Biological Buffer to Coordination Chemistry: New 1D and 3D Coordination Polymers with [Cu4(Hbes)4] Cores for Mild Hydrocarboxylation of Alkanes. Inorg. Chem. 2010, 49, 6390u20136392. DOI: 10.1021 ic1007999. - [18] Sotnik, S. A.; Polunin, R. A.; Kiskin, M. A.; **Kirillov, A. M.**; Dorofeeva, V. N.; Gavrilenko, K. S.; Eremenko, I. L.; Novotortsev, V. M.; Kolotilov, S. V. Heterometallic Coordination Polymers Assembled from Trigonal Trinuclear Fe 2 Ni-Pivalate Blocks and Polypyridine Spacers: Topological Diversity, Sorption, and Catalytic Properties. Inorg. Chem. 2015, 54, 5169u20135181. DOI: 10.1021 ic503061z.  The hydrothermal synthesis method has been widely used in the synthesis of coordination polymers with high yield and good crystallinity [20u201324]. - [21] Gu, J. Z.; Liang, X. X.; Cai, Y.; Wu, J.; Shi, Z. F.; **Kirillov, A. M.** Hydrothermal Assembly, Structures, Topologies, Luminescence, and Magnetism of a Novel Series of Coordination Polymers Driven by a Trifunctional Nicotinic Acid Building Block. Dalton Trans. 2017, 46, 10908u201310925. DOI: 10.1039 C7DT01742A. - [22] Gu, J. Z.; Cui, Y. H.; Wu, J.; **Kirillov, A. M.** A Series of Mixed-Ligand 2D and 3D Coordination Polymers Assembled from a Novel Multifunctional Pyridine-Tricarboxylate Building Block: Hydrothermal Syntheses, Structural and Topological Diversity, and Magnetic and Luminescent Properties. RSC Adv. 2015, 5, 78889u201378901. DOI: 10.1039 C5RA13582F. See also [Dong et al (2021)] . Is it possible to ask who edited and reviewed this manuscript? , 
 I will belatedly add that the weird terms in the Methods paragraphs are often found in [the products of a prolific papermill] .  Next, three different breast cancer cell lines BT474, SKBr-3, and ZR-75-30 in the logarithmic growth stage were collected and cultured into plates of 96-well with the **ultimate destiny** is 5 u0006 10^5 cells per well. Then, the cancer cells were treated with nano 1 for one day. After the therapy, the cancer cells were collected, washed and the total RNA in the treated cells was extracted via TRIzol Reagent under manufactureru2019s instruction. The concentration of the total RNA was measured by the OD260 OD280 ratio, and RNA was then reverse transcripted into cDNA with a high-capacity cDNA reverse transcription kit. Ultimately, the miR-16-1 relative expression in cancer cells was determined by SYBR Green Master Mix after compound treatment. 2u0005DDCt method was used for relative quantification from triplicate **preformation**. , 
 According to Table 1, the crystal-structure determination data and parameters for the present compound are in the CCDC database with Deposition Number 1,968,221. The CCDC database informs me that the dataset was deposited by [Meng Qinghua, of Hang Zhou University] . By my reckoning, [Meng Qinghua has deposited 118 crystal structures with CCDC] . Many of them became parts of problematic papers by otherwise-unrelated teams of authors, including this one. ,