Give The Designer The Clap it Deserves!

Neisseria gonorrhoeae infection in the human endocervical tissue is visualized by immunofluorescence microscopy. Bacterial (red) colonization causes columnar endocervical epithelial cells to shed and lose the barrier function, which allows bacteria to enter the endocervical tissue. Frozen tissue sections were stained for immunofluorescence with specific antibodies to the apical junctional protein ZO1 (green) and N. gonorrhoeae (red) and the nuclear dye DAPI (blue).

Credit: Liang-Chun Wang,
Department of Cell biology and Molecular Genetics,
University of Maryland, USA

Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation

The Intelligent (sic) Designer really does deserve a big clap! It has come up with a brilliant solution to the problem it caused by its lack of a plan!

You see, the Intelligent (sic) Designer, that imaginary being so beloved of creationists but definitely not God because that would make it religion, not science, wants to make life unpleasant for humans (for strictly scientific reasons, obviously, and nothing to do with The Fall because that's religion) so it designed nasty little organisms like Neisseria gonorrhoeae to infect them when they had sex because it doesn't like them having sex the way it designed them to.

The trouble was, in a forgetful moment, it had designed humans so they could cope with nasty little organisms like N. gonorrhoeae and not be made sick by them. Now though, it has briiantly redesigned N. gonorrhoeae so it gets around the protection if gave humans.

In an open access paper published in PLOS Pathogens today, a team of scientists led by Liang-Chun Wang of the University of Maryland, College Park, have worked out how it got around the problem it had created. It does it by exploiting the very defence mechanism the Intelligent (sic) designer designed in the first place.

Abstract
Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells. We found that GC colonization causes endocervical epithelial cells to shed. The shedding results from the disassembly of the apical junctions that seal the epithelial barrier. Apical junction disruption and epithelial exfoliation increase GC penetration into the endocervical epithelium without reducing bacterial adherence to and invasion into epithelial cells. Both epithelial exfoliation and junction disruption require the activation and accumulation of non-muscle myosin II (NMII) at the apical surface and GC adherent sites. GC inoculation activates NMII by elevating the levels of the cytoplasmic Ca²⁺ and NMII regulatory light chain phosphorylation. Piliation of GC promotes, but the expression of a GC opacity-associated protein variant, OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII activation and reorganization and Ca²⁺ flux. The inhibitory effects of OpaH lead to reductions in junction disruption, epithelial exfoliation, and GC penetration. Therefore, GC phase variation can modulate infection in the human endocervix by manipulating the activity of NMII and epithelial exfoliation.

Author summary
Neisseria gonorrhoeae (GC) infects human genital epithelium causing gonorrhea, a common sexually transmitted infection. Gonorrhea is a critical public health issue due to increased prevalence of antibiotic-resistant strains. Because humans are the only host for GC, a lack of a human infection model has been a major obstacle to our understanding of GC infection. Here we use a human tissue explant model to examine the mechanism by which GC infect the human endocervix, the primary site for GC infection in women. We show that GC penetrate into the human endocervix by activating the actin motor myosin and epithelial shedding. Myosin activation causes the disruption of the endocervical epithelial barrier by inducing apical junction disassembly and epithelial cell shedding, allowing GC penetration into the human endocervical tissue. GC activate myosin by inducing Ca²⁺-dependent phosphorylation of myosin light chain. We further show that GC can enhance and reduce the penetration by expressing pili and the opacity-associated protein that promotes and inhibits myosin activation, respectively. Our study is the first demonstration of GC penetration into the human endocervix. Our results provide new insights into the mechanism by which GC manipulate signaling and cytoskeletal apparatus in epithelial cells to achieve penetrating and non-penetrating infection.

Wang L-C, Yu Q, Edwards V, Lin B, Qiu J, Turner JR, et al. (2017)
Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation.
PLoS Pathog 13(4): e1006269. https://doi.org/10.1371/journal.ppat.1006269

Copyright © 2017 Wang et al. Reprinted under Creative Commons Attribution 4.0 International licence (CC BY 4.0).

Basically, the normal defence mechanism against infection in the human reproductive tract is to shed the infected cells from the lining whilst keeping the barrier behind them intact. N. gonorrhoeae has exploited this by breaking the barrier first, so that when the cells are shed, instead of taking the bacteria bacteria away with the dead cell, it now created a route through the epithelium and into the host so it can cause maximum distress and illness.

Neat huh! This designer certainly deserves the clap it gave us!

Yes! Of course I'm being sarcastic! Nothing that could be described as intelligent, and especially something that could be described as benevolent, would have to solve a problem it created in the first place just so it can cause suffering because it has an obsessive disgust of sex, which it designed us to have.

This system quite obviously evolved by a mindless process without a plan and nothing that could be regarded as morality. This is exactly the sort of thing we would expect of evolution.

'via Blog this'

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