Nanomechanical mechanisms of Lyme disease spirochete motility enhancement in extracellular matrix

Abstract

As opposed to pathogens passively circulating in the body fluids of their host, pathogenic species within the Spirochetes phylum are able to actively coordinate their movement in the host to cause systemic infections. Based on the unique morphology and high motility of spirochetes, we hypothesized that their surface adhesive molecules might be suitably adapted to aid in their dissemination strategies. Designing a system that mimics natural environmental signals, which many spirochetes face during their infectious cycle, we observed that a subset of their surface proteins, particularly Decorin binding protein (Dbp) A/B, can strongly enhance the motility of spirochetes in the extracellular matrix of the host. Using single-molecule force spectroscopy, we disentangled the mechanistic details of DbpA/B and decorin/laminin interactions. Our results show that spirochetes are able to leverage a wide variety of adhesion strategies through force-tuning transient molecular binding to extracellular matrix components, which concertedly enhance spirochetal dissemination through the host.

Plant-Derived Anti-Human Epidermal Growth Factor Receptor 2 Antibody Suppresses Trastuzumab-Resistant Breast Cancer with Enhanced Nanoscale Binding

“…with C eff being the effective concentration of antibodies coupled to the AFM tip. 27,32 C eff is given by…”

Human infections with neglected vector-borne pathogens in China: A systematic review

“…As Rickettsiales bacteria are microorganisms that share features of both bacteria and viruses which are comprised of obligate intracellular parasitic bacteria, 38 , 39 and Spirochaetales bacteria do not possess bacterial adhesins and differ from most other motile pathogenic bacteria in that the spirochetes miss external appendages that are commonly required for bacterial motility. 40 In order to distinguish vector-borne diseases caused by different bacteria, we divided vector-borne bacteria into Rickettsiales bacteria, Spirochaetales bacteria and other bacteria in this review. 41 , 42 , 43 …”

“…As Rickettsiales bacteria are microorganisms that share features of both bacteria and viruses which are comprised of obligate intracellular parasitic bacteria, 38,39 and Spirochaetales bacteria do not possess bacterial adhesins and differ from most other motile pathogenic bacteria in that the spirochetes miss external appendages that are commonly required for bacterial motility. 40 In order to distinguish vectorborne diseases caused by different bacteria, we divided vector-borne bacteria into Rickettsiales bacteria, Spirochaetales bacteria and other bacteria in this review. 41−43 Since the pathogen names and taxonomy might have changed along the study years, online taxonomy search websites, including International Committee on Taxonomy of Viruses (ICTV) (https://talk.ictvonline.org/) and National Center for Biotechnology Information (NCBI) Taxonomy (https://www.ncbi.nlm.nih.gov/taxonomy/) were used to update the current taxonomy classification.…”

Effects of outer surface lipoproteins on the nanomechanical properties of Lyme borrelia

“…AFM has been successfully employed to study characteristics of B. burgdorferi in a handful of studies, including changing characteristics of nanomechanical properties such as adhesion force in the presence of antibodies and complement system, as well as the role of periplasmic flagella in maintaining cellular integrity under external stress [39,40]. AFM was also recently employed to measure the mechanistic properties of the B. burgdorferi adhesins DbpA/B and its substrate decorin [41]. These studies have provided important insights into how the structural integrity of the cell is maintained under stress and how adhesins might enhance the dissemination of B. burgdorferi throughout the host.…”