Structural and Functional Characterization of the FimH Adhesin of Uropathogenic Escherichia coli and Its Novel Applications

Research Article

J Bacteriol Mycol. 2020; 7(5): 1142.

Structural and Functional Characterization of the FimH Adhesin of Uropathogenic Escherichia coli and Its Novel Applications

Neamati F1, Moniri R2*, Khorshidi A1 and Saffari M1

¹Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

²Department of Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Qutb Ravandi Boulevard, Kashan, Iran

*Corresponding author: Moniri R, Department of Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Qutb Ravandi Boulevard, Kashan, Iran

Received: June 05, 2020; Accepted: July 03, 2020; Published: July 10, 2020

Abstract

Type 1 fimbriae are responsible for bacterial pathogenicity and biofilm production, which are important virulence factors in uropathogenic Escherichia coli strains. Many articles are published on FimH, but each examined a specific aspect of this protein. The current review study aimed at focusing on structure and conformational changes and describing efforts to use this protein in novel potential treatments for urinary tract infections, typing methods, and expression systems. The current study was the first review that briefly and effectively examined issues related to FimH adhesin.

Keywords: Uropathogenic E. coli; FimH Adhesion; FimH Typing; Conformation Switch; FimH Antagonists

Abbreviations

UTIs: Urinary Tract Infections; UPEC: Uropathogenic E. Coli; IBCs: Intracellular Bacterial Communities; QIR: Quiescent Intracellular Reservoir; LD: Mannose-Binding Lectin; PD: Fimbria- Incorporating Pilin; MBP: Mannose-Binding Pocket; LIBS: Ligand- Induced Binding Site; THP: Tamm-Horsfall Glycoprotein; MN: Mannan Yeast; MI: Mono-Mannose; MIL: Slow M1-binding; M1H: High M1-binding; SNPs: Single-Nucleotide Polymorphisms; PFGE: Pulsed-Field Gel Electrophoresis; MLST: Multilocus Sequence Typing; RFLP: Restriction Fragment Length Polymorphism; WGS: Whole-Genome Sequencing; ERIC: Enterobacterial Repetitive Intergenic Consensus-PCR; AIEC: Adherent and Invasive E. Coli

Introduction

Urinary Tract Infections (UTIs) are mostly caused by uropathogenic Escherichia coli (UPEC) strains. The UPEC binds the urothelium with type 1 fimbriae encoded by the fim operon [1]. Type 1 fimbriae are expressed in over 95% of all E. coli strains and this expression is partially regulated by phase variable inversion of the genomic structure comprising the fimS promoter, which eventually results in phase ON (expression) or OFF (nonexpression) orientations [1,2]. The two fimC and fimD genes play a role in transcription and assembly of type 1 fimbriae. The fimCencoded chaperone protein transports fimbrial proteins through the periplasmic space, and the fimD-encoded protein acts as an usher (Figure1) [3]. This fimbria has four different subunits, including FimA, FimH, FimF, and FimG. The bulk of the structure is FimA that is polymerized into a right-handed helical fibril and has a variable structure [4]. FimH is the fimbrial adhesin that is at the tip of the organelle and is highly conserved genetically and antigenically among Enterobacteriaceae genera. Perhaps FimF and FimG are required for the integration of FimH into fimbria [4,5]. Bacteria expressing type 1 fimbriae can agglutinate guinea pig red blood cells under mannosesensitive conditions that require FimH to induce this phenotype [6]. FimH proteins play important roles in UPEC pathogenicity and the formation of bacterial biofilms [7]. FimH binds to mannosylated uroplakin proteins in the bladder lumen and invades into the superficial umbrella cells [8]. After the invasion, UPEC is expelled out of the cell in a TLR4 dependent process, or escape into the cytoplasm [9]. The rapid proliferation of bacteria under complex pathways inside the cell leads to the formation of intracellular bacterial communities (IBCs) that morphologically have distinct structures with biofilm characteristics that protect UPEC against the immune system [8]. In the sequel, UPEC forms another type of intracellular structure called the quiescent intracellular reservoir (QIR). QIRs are small collections of UPEC bacteria (up to 12 bacteria) with slow growth, known as recurrent UTIs agents [10]. Also, FimH is involved in the dissemination of infection to other tissues. For example, FimH is the cause of UPEC localization in the brain microvascular endothelium and invade to meninges [11]. The current review study aimed at overviewing FimH adhesin and emphasizing some general aspects of its biogenesis and role in bacterial colonization of host cell surfaces and virulence factors. The current study focused on the essential content of FimH, including the structure, mutations, and applications in biotechnology, subtyping, and treatment of UTIs.