The Ferric Citrate Uptake System Encoded in a Novel bla CTX-M-3- and bla TEM-1-Harboring Conjugative Plasmid Contributes to the Virulence of Escherichia coli

Wen-Chun Huang; Min-Yi Wong; Ssu-Han Wang; Masayuki Hashimoto; Meng-He Lin; Mei-Feng Lee; Jiunn-Jong Wu; Ming-Cheng Wang; Wei-Hung Lin; Shuen-Lin Jeng; Jiun-Ling Wang; Ya-Lei Chen; Ching-Hao Teng

doi:10.3389/fmicb.2021.667782

The Ferric Citrate Uptake System Encoded in a Novel bla _CTX-M-3- and bla _TEM-1-Harboring Conjugative Plasmid Contributes to the Virulence of Escherichia coli

Front Microbiol. 2021 May 26:12:667782. doi: 10.3389/fmicb.2021.667782. eCollection 2021.

Authors

Wen-Chun Huang¹, Min-Yi Wong¹, Ssu-Han Wang¹, Masayuki Hashimoto^{1

2

3}, Meng-He Lin¹, Mei-Feng Lee^{1

4}, Jiunn-Jong Wu⁵, Ming-Cheng Wang⁶, Wei-Hung Lin⁷, Shuen-Lin Jeng⁸, Jiun-Ling Wang^{9

10}, Ya-Lei Chen⁴, Ching-Hao Teng^{1

2

3

11}

Affiliations

¹ Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan.
⁵ Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁸ Department of Statistics, Institute of Data Science, Center for Innovative FinTech Business Models, National Cheng Kung University, Tainan, Taiwan.
⁹ Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
¹⁰ Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹¹ Center of Allergy and Clinical Immunology Research (ACIR), National Cheng Kung University, Tainan, Taiwan.

Abstract

Escherichia coli is one major cause of bacterial infections and can horizontally acquire antimicrobial resistance and virulence genes through conjugation. Because conjugative plasmids can rapidly spread among bacteria of different species, the plasmids carrying both antimicrobial resistance and virulence genes may pose a significant threat to public health. Therefore, the identification and characterization of these plasmids may facilitate a better understanding of E. coli pathogenesis and the development of new strategies against E. coli infections. Because iron uptake ability is a potential virulence trait of bacteria, we screened for E. coli conjugative plasmids able to confer both iron uptake ability and ampicillin resistance. The plasmid pEC41, which was derived from the bacteremia clinical isolate EC41, was identified. EC41, which carried the fimH27 allele, belonged to sequence type (ST) 405 and phylogroup D. According to the sequencing analyses, pEC41 was 86 kb in size, and its backbone structure was almost identical to that of another highly conjugative plasmid, pCTX-M3, in which the extended-spectrum β-lactamase gene bla _CTX-M-3 was originally identified. pEC41 carried bla _CTX-M-3 and bla _TEM-1. The ferric citrate uptake (fec) system was identified in pEC41 and was responsible for conferring iron uptake ability. The fec system contributes to the pathogenesis of EC41 in systemic infections but not in urinary tract infections (UTIs). However, this system promoted competitive fitness of a cystitis-associated clinical isolate to colonize urinary tracts. Additionally, the distribution of the fec system was related to E. coli isolates associated with human bacteremia and UTIs. In summary, the present study identified a novel conjugative plasmid, pEC41, which conferred both antimicrobial resistance and an extra iron uptake ability to E. coli. The iron uptake ability was encoded in the fec system and contributed to E. coli pathogenesis. This study is the first to show that the fec system is a virulence factor in E. coli.

Keywords: E. coli; ESBL; bacteremia; blaCTX–M–3; conjugative plasmid; ferric citrate; iron uptake system; urinary tract infections.