A Sticky Chain Model of the Elongation and Unfolding of Escherichia coli P Pili under Stress

Andersson, Magnus; Fällman, Erik; Uhlin, Bernt Eric; Axner, Ove

doi:10.1529/biophysj.105.074674

Cited by 59 publications

(122 citation statements)

References 48 publications

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“…As for the later two phases, a sticky-chain model, which describes the stretched behaviors of a type 1 fimbria or a P fimbria (1,23), is suitable to describe the later two phases of a type 3 fimbria. Conceptually, in the uncoiling phase, closed layer-to-layer (LL) bonds in the helix-like structure of a type 3 fimbria are opened successively with the uncoiling force of 66 pN.…”

Section: Discussionmentioning

confidence: 99%

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Structural and Mechanical Properties of Klebsiella pneumoniae Type 3 Fimbriae

et al. 2011

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This study investigated the structural and mechanical properties of Klebsiella pneumoniae type 3 fimbriae, which constitute a known virulence factor for the bacterium. Transmission electron microscopy and optical tweezers were used to understand the ability of the bacterium to survive flushes. An individual K. pneumoniae type 3 fimbria exhibited a helix-like structure with a pitch of 4.1 nm and a three-phase force-extension curve. The fimbria was first nonlinearly stretched with increasing force. Then, it started to uncoil and extended several micrometers at a fixed force of 66 ؎ 4 pN (n ‫؍‬ 22). Finally, the extension of the fimbria shifted to the third phase, with a characteristic force of 102 ؎ 9 pN (n ‫؍‬ 14) at the inflection point. Compared with the P fimbriae and type 1 fimbriae of uropathogenic Escherichia coli, K. pneumoniae type 3 fimbriae have a larger pitch in the helix-like structure and stronger uncoiling and characteristic forces.

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Section: Discussionmentioning

confidence: 99%

“…In this phase, another particular stretching force of the fimbria occurs at the inflection point (x c ) of the S-shaped FEC, where the slope is minimal. This particular force is denoted the characteristic force (F ch ), which for P fimbriae is 67 pN (1).…”

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confidence: 99%

Structural and Mechanical Properties of Klebsiella pneumoniae Type 3 Fimbriae

et al. 2011

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“…9 They have evolved into a three-dimensional helix-like structure, the PapA rod, [10][11][12][13][14] that can be successively and significantly elongated and/or unfolded when exposed to external forces. [13][14][15][16][17][18] The PapA rod is a thin micrometer-long helical rod composed of ~103 subunits that are coupled to their nearest neighbors by a β-strand complementation and combined in a right handed helical arrangement with 3.28 units per turn. [11][12][13][14] It has been hypothesized that the structure of the P pili, with its flexible structure and intricate unfolding mechanism, makes it possible for a UPEC bacterium to withstand considerable shear forces by a process in which a large number of pili can support tension simultaneously, despite dissimilar bacterium-to-host distances, 13,14 which, in turn, could explain why they can remain attached to the host tissue even in the presence of considerable urine flows.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13][14] However, because of the specific importance and unique behavior of E. coli P pili, their intrinsic mechanical properties were recently assessed using FMOT, both under conventional (steady-state) and dynamic modes of operation. [15][16][17][18] It was found that the PapA rod possesses a rich flavor of elongation and contraction behavior. For example, in addition to initial elastic stretching, the elongation of a P pilus takes place by a sequential and cooperative unfolding of its PapA rod.…”

Section: Introductionmentioning

confidence: 99%

Force measuring optical tweezers system for long time measurements of P pili stability

et al. 2006

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A force-measuring optical tweezers instrumentation and long time measurements of the elongation and retraction of bacterial fimbriae from Uropathogenic E. coli (UPEC) under strain are presented. The instrumentation is presented in some detail. Special emphasis is given to measures taken to reduce the influence of noise and drifts in the system and from the surrounding, which makes long term force measurements possible. Individual P pili from UPEC bacteria were used as a biological model system for repetitive unfolding and refolding cycles of bacterial fimbriae under equilibrium conditions. P pili have evolved into a three-dimensional helix-like structure, the PapA rod, that can be successively and significantly elongated and/or unfolded when exposed to external forces. The instrumentation is used for characterization of the force-vs.-elongation response of the PapA rod of individual P pili, with emphasis on the long time stability of the forced unfolding and refolding of the helical structure of the PapA rod. The results show that the PapA rod is capable of withstanding extensive strain, leading to a complete unfolding of the helical structure, repetitive times during the life cycle of a bacterium without any noticeable alteration of the mechanical properties of the P pili. This function is believed to be importance for UPEC bacteria in vivo since it provides a close contact to a host cell (which is an initial step of invasion) despite urine cleaning attempts.

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“…Recent studies suggest that the quaternary structure of a fimbrial shaft plays an additional deterministic role in colonization, inasmuch as the shaft of certain ETEC fimbriae, as well as those of other pathogenic E. coli, is adapted to organ-specific biomechanical and structural features. Despite their differences in biogenesis and assembly processes, when analyzed biomechanically, ETEC-expressed fimbriae unwind at a characteristic low-unwinding steady force of Ͻ20 pN (7,8), while fimbriae expressed by extraintestinal pathogenic E. coli (ExPEC), such as type 1, P, and S fimbriae, require a steady force of Ͼ20 pN to unwind (7,(9)(10)(11)(12).…”

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Antibodies Damage the Resilience of Fimbriae, Causing Them To Be Stiff and Tangled

et al. 2017

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As adhesion fimbriae are a major virulence factor for many pathogenic Gram-negative bacteria, they are also potential targets for antibodies. Fimbriae are commonly required for initiating the colonization that leads to disease, and their success as adhesion organelles lies in their ability to both initiate and sustain bacterial attachment to epithelial cells. The ability of fimbriae to unwind and rewind their helical filaments presumably reduces their detachment from tissue surfaces with the shear forces that accompany significant fluid flow. Therefore, the disruption of functional fimbriae by inhibiting this resilience should have high potential for use as a vaccine to prevent disease. In this study, we show that two characteristic biomechanical features of fimbrial resilience, namely, the extension force and the extension length, are significantly altered by the binding of antibodies to fimbriae. The fimbriae that were studied are normally expressed on enterotoxigenic Escherichia coli, which are a major cause of diarrheal disease. This alteration in biomechanical properties was observed with bivalent polyclonal antifimbrial antibodies that recognize major pilin subunits but not with the Fab fragments of these antibodies. Thus, we propose that the mechanism by which bound antibodies disrupt the uncoiling of natural fimbria under force is by clamping together layers of the helical filament, thereby increasing their stiffness and reducing their resilience during fluid flow. In addition, we propose that antibodies tangle fimbriae via bivalent binding, i.e., by binding to two individual fimbriae and linking them together. Use of antibodies to disrupt physical properties of fimbriae may be generally applicable to the large number of Gram-negative bacteria that rely on these surface-adhesion molecules as an essential virulence factor. IMPORTANCE Our study shows that the resiliency of colonization factor antigen I (CFA/I) and coli surface antigen 2 (CS2) fimbriae, which are current targets for vaccine development, can be compromised significantly in the presence of antifimbrial antibodies. It is unclear how the humoral immune system specifically interrupts infection after the attachment of enterotoxigenic Escherichia coli (ETEC) to the epithelial surface. Our study indicates that immunoglobulins, in addition to their welldocumented role in adaptive immunity, can mechanically damage the resilience of fimbriae of surface-attached ETEC, thereby revealing a new mode of action. Our data suggest a mechanism whereby antibodies coat adherent and free-floating bacteria to impede fimbrial resilience. Further elucidation of this possible mechanism is likely to inform the development and refinement of preventive vaccines against ETEC diarrhea.KEYWORDS pili, IgG, vaccine, CFA/I, CS2, optical tweezers

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A Sticky Chain Model of the Elongation and Unfolding of Escherichia coli P Pili under Stress

Cited by 59 publications

References 48 publications

Structural and Mechanical Properties of Klebsiella pneumoniae Type 3 Fimbriae

Structural and Mechanical Properties of Klebsiella pneumoniae Type 3 Fimbriae

Force measuring optical tweezers system for long time measurements of P pili stability

Antibodies Damage the Resilience of Fimbriae, Causing Them To Be Stiff and Tangled

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