MCR Expression Conferring Varied Fitness Costs on Host Bacteria and Affecting Bacteria Virulence
Wan Li,
Zhihai Liu,
Wenjuan Yin,
Lu Yang,
Lu Qiao,
Shikai Song,
Zhuoren Ling,
Ruicheng Zheng,
Congming Wu,
Yang Wang,
Jianzhong Shen
Affiliations
Wan Li
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Zhihai Liu
College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, China
Wenjuan Yin
Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-Autoimmune Diseases of Hebei Province, College of Basic Medical Science, Hebei University, Baoding 071002, China
Lu Yang
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Lu Qiao
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Shikai Song
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Zhuoren Ling
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Ruicheng Zheng
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Congming Wu
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Yang Wang
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Jianzhong Shen
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100193, China
Since the first report of the plasmid-mediated, colistin-resistant gene, mcr-1, nine mcr genes and their subvariants have been identified. The spreading scope of mcr-1~10 varies greatly, suggesting that mcr-1~10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly similar to mcr-1 and -2, and mcr-7~10 are highly similar to mcr-3 and -4. We compared the expression effects of MCR-1~5 on bacteria of common physiological background. The MCR-1-expressing strain showed better growth than did MCR-2~5-expressing strains in the presence of colistin. LIVE/DEAD staining analysis revealed that MCR-3~5 expression exerted more severe fitness burdens on bacteria than did MCR-1 and -2. Bacteria expressing MCRs except MCR-2 showed enhanced virulence with increased epithelial penetration ability determined by trans-well model (p Galleria mellonella model, which may have resulted from bacterial membrane damage and different levels of lipopolysaccharide (LPS) release due to MCR expression. Collectively, MCR-1-expressing strain showed the best survival advantage of MCR-1~5-expressing strains, which may partly explain the worldwide distribution of mcr-1. Our results suggested that MCR expression may cause increased bacterial virulence, which is alarming, and further attention will be needed to focus on the control of infectious diseases caused by mcr-carrying pathogens.
