Mycoplasma genitalium adhesin P110 binds sialic-acid human receptors

Aparicio, David; Torres-Puig, Sergi; Ratera, Mercè; Querol, Enrique; Piñol, Jaume; Pich, Óscar Q.; Fita, Ignacio

doi:10.1038/s41467-018-06963-y

Cited by 34 publications

(62 citation statements)

References 67 publications

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“…1). The first transmembrane region (spanning the N-terminus), and the last transmembrane region (spanning the C-terminus) have been identified in previous studies of P1 32,36,66 , and a P1 paralog of Mycoplasma genitalium 73 . The glycosaminoglycan binding sites consist of reiterated copies of positively charged amino acids that are likely to be important in interactions with sulphated derivatives of heparin and heparan sulfate.…”

Section: Resultsmentioning

confidence: 84%

“…, and transmembrane domains (TmD, yellow boxes, TmD 1 predicted by TMpred 66 , TmD 2 previously predicted 32 , TmD 3 previously predicted 36 , and TmD 4 previously predicted in a P1 paralog 73 ) are shown within the black bar. Putative transmembrane domains and the location of 15 subregions of P1 (grey 'RP' boxes) expressed as recombinant proteins from an earlier study 55 are shown.…”

Section: Immunoblot Of M Pneumoniae Cell Lysates Using Anti-p1 Serummentioning

confidence: 99%

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Cell surface processing of the P1 adhesin of Mycoplasma pneumoniae identifies novel domains that bind host molecules

Widjaja

Berry

Jarocki

et al. 2020

Sci Rep

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Mycoplasma pneumoniae is a genome reduced pathogen and causative agent of community acquired pneumonia. The major cellular adhesin, P1, localises to the tip of the attachment organelle forming a complex with P40 and P90, two cleavage fragments derived by processing Mpn142, and other molecules with adhesive and mobility functions. LC-MS/MS analysis of M. pneumoniae M129 proteins derived from whole cell lysates and eluents from affinity matrices coupled with chemically diverse host molecules identified 22 proteoforms of P1. Terminomics was used to characterise 17 cleavage events many of which were independently verified by the identification of semitryptic peptides in our proteome studies and by immunoblotting. One cleavage event released 1597 tSAAKpGApRppVppKpGApKppVQppKKpA 1627 from the C-terminus of P1 and this peptide was shown to bind to a range of host molecules. A smaller synthetic peptide comprising the C-terminal 15 amino acids, 1613 pGApKppVQppKKpA 1627 , selectively bound cytoskeletal intermediate filament proteins cytokeratin 7, cytokeratin 8, cytokeratin 18, and vimentin from a native A549 cell lysate. Collectively, our data suggests that ectodomain shedding occurs on the surface of M. pneumoniae where it may alter the functional diversity of P1, Mpn142 and other surface proteins such as elongation factor Tu via a mechanism similar to that described in Mycoplasma hyopneumoniae. The attachment organelle is a structurally and functionally sophisticated component of the M. pneumoniae cell that is responsible for the assembly of proteins essential for motility and adherence 1-8. An extensive list of host molecules including fibronectin 9-13 , fibrinogen 10-14 , plasminogen 11-13,15-17 , lactoferrin 10-12 , laminin 10-12 , and vitronectin 10-13 interact with surface accessible adhesins in M. pneumoniae. Other less well-defined host molecules include sialylated molecules 18 , oligosaccharides 19 , glycolipids 20 , and glycoproteins 21. The gene mpn141 encoding the major adhesin P1 is located in the same operon along with mpn140 and mpn142 and these three genes constitute a polycistronic transcriptional unit 22,23. mpn140 encodes for a 28 kDa putative phosphoesterase 24 and while it has been shown to degrade nanoRNA and dephosphorylate 3′-phosphoadenosine 5′-phosphate to AMP 25 , no role in adherence has been assigned for this protein. mpn142 generates a 130 kDa product (Mpn142) that is cleaved into two fragments of 40 kDa (P40) and 90 kDa (P90) immediately after or concurrent with translation 26,27. The cleavage event in Mpn142, first described over 25 years ago, was the first in what is now known to be a highly processed molecule on the surface of M. pneumoniae 28. P1 is a remarkably versatile molecule and the subject of numerous studies over the past 30 years. The only cleavage event that has been accurately assigned to P1 is the removal of the N-terminal 59 amino acids as a leader peptide 29. Molecular cross-linking and immunogold-labelling studies indicated that P1 forms a complex with P30, P40, and P90 ...

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Section: Resultsmentioning

confidence: 84%

Section: Immunoblot Of M Pneumoniae Cell Lysates Using Anti-p1 Serummentioning

confidence: 99%

Cell surface processing of the P1 adhesin of Mycoplasma pneumoniae identifies novel domains that bind host molecules

Widjaja

Berry

Jarocki

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The adhesin complex in M. genitalium is also composed of a dimer of heterodimers constructed by P110 and P140, the homologs of P1 adhesin and P90, respectively (53). P110 has a binding site for SOs, so one adhesin complex binds two SOs (31). The adhesin complex of M. gallisepticum is assumed to have two binding sites for SOs because it is composed of CrmA and GapA, the homologs of P110 and P140, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…P90 is encoded in tandem with P1 adhesin and is cleaved from another protein, P40, for maturation (29, 30). A recent study shows that the homolog of P40/P90 in M. genitalium , P110, has a binding pocket of sialylated oligosaccharides (SOs) (31), which are binding targets for Mycoplasma infection and gliding. The mechanism of the gliding motility has been proposed as an ‘inchworm model,’ in which a cell catches SOs on solid surfaces through the adhesin complexes and is propelled by the repetitive extensions and retractions of the internal core (3, 7, 8).…”

Section: Introductionmentioning

confidence: 99%

Behaviors and Energy Source ofMycoplasma gallisepticumGliding

Mizutani

Miyata

2019

Preprint

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Mycoplasma gallisepticum, an avian-pathogenic bacterium, glides on host tissue surfaces by using a common motility system with Mycoplasma pneumoniae. In the present study, we observed and analyzed the gliding behaviors of M. gallisepticum in detail by using optical microscopes. M. gallisepticum glided at a speed of 0.27 ± 0.09 µm/s with directional changes relative to the cell axis of 0.6 ± 44.6 degrees/5 s without the rolling of the cell body. To examine the effects of viscosity on gliding, we analyzed the gliding behaviors under viscous environments. The gliding speed was constant in various concentrations of methylcellulose but was affected by Ficoll. To investigate the relationship between binding and gliding, we analyzed the inhibitory effects of sialyllactose on binding and gliding. The binding and gliding speed sigmoidally decreased with sialyllactose concentration, indicating the cooperative binding of the cell. To determine the direct energy source of gliding, we used a membrane-permeabilized ghost model. We permeabilized M. gallisepticum cells with Triton X-100 or Triton X-100 containing ATP and analyzed the gliding of permeabilized cells. The cells permeabilized with Triton X-100 did not show gliding; in contrast, the cells permeabilized with Triton X-100 containing ATP showed gliding at a speed of 0.014 ± 0.007 μm/s. These results indicate that the direct energy source for the gliding motility of M. gallisepticum is ATP.IMPORTANCEMycoplasmas, the smallest bacteria, are parasitic and occasionally commensal. Mycoplasma gallisepticum is related to human pathogenic Mycoplasmas—Mycoplasma pneumoniae and Mycoplasma genitalium—which causes so-called ‘walking pneumonia’ and non-gonococcal urethritis, respectively. These Mycoplasmas trap sialylated oligosaccharides, which are common targets among influenza viruses, on host trachea or urinary tract surfaces and glide to enlarge the infected areas. Interestingly, this gliding motility is not related to other bacterial motilities or eukaryotic motilities. Here, we quantitatively analyze cell behaviors in gliding and clarify the direct energy source. The results provide clues for elucidating this unique motility mechanism.

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“…In mycoplasmas, cytoadhesins are often involved in several key biological functions. Beside their crucial roles in cell adhesion, they are also important for invasion, colonization, and dissemination within the hosts [47]. This prompted us to test the translocation of strain HB0801 across epithelial cell monolayers.…”

Section: Discussionmentioning

confidence: 99%

Mbov_0503 Encodes a Novel Cytoadhesin that Facilitates Mycoplasma bovis Interaction with Tight Junctions

et al. 2020

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Molecules contributing to microbial cytoadhesion are important virulence factors. In Mycoplasma bovis, a minimal bacterium but an important cattle pathogen, binding to host cells is emerging as a complex process involving a broad range of surface-exposed structures. Here, a new cytoadhesin of M. bovis was identified by producing a collection of individual knock-out mutants and evaluating their binding to embryonic bovine lung cells. The cytoadhesive-properties of this surface-exposed protein, which is encoded by Mbov_0503 in strain HB0801, were demonstrated at both the mycoplasma cell and protein levels using confocal microscopy and ELISA. Although Mbov_0503 disruption was only associated in M. bovis with a partial reduction of its binding capacity, this moderate effect was sufficient to affect M. bovis interaction with the host-cell tight junctions, and to reduce the translocation of this mycoplasma across epithelial cell monolayers. Besides demonstrating the capacity of M. bovis to disrupt tight junctions, these results identified novel properties associated with cytoadhesin that might contribute to virulence and host colonization. These findings provide new insights into the complex interplay taking place between wall-less mycoplasmas and the host-cell surface.

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Mycoplasma genitalium adhesin P110 binds sialic-acid human receptors

Cited by 34 publications

References 67 publications

Cell surface processing of the P1 adhesin of Mycoplasma pneumoniae identifies novel domains that bind host molecules

Cell surface processing of the P1 adhesin of Mycoplasma pneumoniae identifies novel domains that bind host molecules

Behaviors and Energy Source ofMycoplasma gallisepticumGliding

Mbov_0503 Encodes a Novel Cytoadhesin that Facilitates Mycoplasma bovis Interaction with Tight Junctions

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