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By Susha Cheriyedath, M.Sc. Jul 31 2023 Reviewed by Benedette Cuffari, M.Sc.

A recent study published in PLOS Pathogens identifies the Leptospira membrane protein L36 (MPL36) as essential for its pathogenesis and, as a result, a potential target for future diagnostics and prophylactics.

Study:  MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection.  Image Credit: Kateryna Kon / Shutterstock.com Background

The human plasminogen (PLG) system provides a proteolytic substrate for pathogen invasiveness and tissue damage, thereby increasing the virulence of various bacterial species. Sequestration of PLG and activation into plasmin (PLA) is important for bacterial survival, as PLA degrades fibrin clots, extracellular matrix (ECM) molecules, and the host's innate immunological proteins to enable bacteria to spread and evade immune responses ultimately.

Leptospirosis, a life-threatening infectious disease, is a zoonotic disease that accounts for over one million infections and about 60,000 deaths each year throughout the world. In severe forms of leptospirosis, patients will often experience severe hemorrhaging and acute kidney injury.

Leptospira enter the host through injured skin or mucous membranes and subsequently travel through viscous environments to ultimately reach the bloodstream. Thereafter, Leptospira participate in cellular adhesion, which is mediated by various surface proteins that interact with ECM components.

Previous studies indicate that many Leptospira proteins act as PLG receptors, some of which include outer membrane proteins (OMPs) like endostatin-like protein A (LenA), as well as Leptospiral immunoglobulin-like proteins A (LigA), LiGB, and LipL32.

To date, there remains a lack of data on the pathogenesis of leptospirosis, which has prevented the development of sensitive diagnostic instruments and efficient prophylactic treatments. The present study reports that MPL36 binds with PLG, promotes adherence to host cells, and degrades fibrinogen by converting bound PLG to PLA. About the study

The current study utilized Leptospira interrogans serovar Manilae strain L495 and its mutant stains, including Manilae mpl36 mutant complemented strain (Δmpl36+) and Leptospira biflexa serovar Patoc strain Patoc 1. These strains were cultured in Madin-Darby canine kidney (MDCK) cells, following which their growth curves were analyzed using dark-field microscopy, motility, and immunoblot assays.  

Recombinant MPL36 (rMPL36) protein was produced using E. coli expression. Intrinsic tryptophan fluorescence spectroscopy and nickel affinity chromatography evaluated the tertiary structure of rMPL36, rMPL36 aa41-305, and rMPL36 aa41-235. The binding capacity of rMPL36 was determined, and the conversion of PLG bound to rMPL36 into active PLA was evaluated.

The binding of rMPL36 to ECM proteins and PLG was determined by staining for fibronectin, laminin, PLG, and bovine serum albumin (BSA). The pathogenicity of Manilae wildtype (WT) and mutant strains was also evaluated in three-week-old male Golden Syrian hamsters. Related StoriesSARS-CoV-2 spike protein's role in lung injury unraveled: promising new approach uncoveredMitochondrial repair protein discovery may lead to new anti-aging treatmentsSalk researchers uncover molecular mechanisms of HIV drug resistance

The tertiary structure of sporulation-related repeat (SPOR) domains from leptospiral species was predicted using AlphaFold and PyMOL software ClustalX to match MPL36 SPOR domain sequences from various Leptospira species. In vivo data was analyzed using Prism 9, Fisher's exact test, and analysis of variance (ANOVA) to ecludate the mechanisms of rMPL36 binding to host components and BSA. MPL36 is a crucial target for leptopsirosis

The motility assay revealed that, as compared to wild-type cells, mpl36 mutant and complemented strains did not significantly differ in their motility or growth characteristics. Immunofluorescence staining confirmed the subcellular localization of MPL36 in Leptospira as an outer membrane protein in both wild-type and complement cells.

Immunoprecipitation studies revealed that rMPL36 exhibited significant binding to both rLigA and rLigB, whereas no binding was observed between rMPL36 and fibronectin nor laminin.

However, rMPL36 was found to effectively bind to human PLG as compared to other recombinant proteins that were used as positive and negative controls. Within rMPL36, the conserved SPOR domain, which is located at the last 70 amino acids of the protein, is essential for the binding between rMPL36 and PLG.

Hamsters that were infected with the wild-type strain died between eight and nine days following infection with Leptospira. Comparatively, mpl36 mutant hamsters who were infected with 108 leptospires survived without exhibiting any symptoms of leptospirosis, thereby demonstrating the significant role of MPL36 in leptospirosis.

Convalescent sera were obtained from Brazilian individuals with laboratory-confirmed severe leptospirosis. To this end, anti-MPL36 immunoglobulin M (IgM) and IgG were observed in leptospirosis patients’ samples as compared to sera from healthy individuals. Study takeaways

MPL36 is an outer membrane Leptospira protein that is capable of binding to PLG, degrading fibrinogen, and facilitating host infection. Despite these findings, additional research is needed to better understand leptospiral pathogenesis and advance diagnostic and prevention strategies. Journal reference: Zhu, W., Passalia, F. J., Hamond, C., et al. (2023). MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection. PLOS Pathogens. doi:10.1371/journal.ppat.1011313 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011313

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Murder arrest after woman stabbed to death in Enfield – as victim named

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Murder arrest after woman stabbed to death in Enfield - as victim named

A woman who was stabbed to death in north London has been named by police – as a man was arrested on suspicion of murder.

Pamela Munro, 45, was found with a stab wound and died at the scene in Ayley Croft, Enfield, on Saturday evening, the Metropolitan Police said.

A 29-year-old man was arrested on suspicion of murder on Monday and is in custody, the force added.

Detective Chief Inspector Neil John said: “Investigating officers have worked relentlessly across the weekend to investigate the circumstances around Pamela’s death.

“We continue to support her family who are understandably devastated.”

GVs from SN footage on 20/04/2025 at scene of murder on 19/04/2025 of woman at Gainsborough House, Ayley Croft, Enfield in north London.
Ingest 25 NM25 SKY SAF ENFIELD MURDER GVS ENFIELD 2045
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Police at the scene at Ayley Croft in Enfield

Read more from Sky News:
Fresh appeal over student’s murder
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The Met Police has asked anyone with information or who was driving through Ayley Court between 6.30pm and 7.30pm on Saturday and may have dashcam footage to contact the force.

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‘British man’ dies after being dragged out of police station in Ecuador – reports

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'British man' dies after being dragged out of police station in Ecuador - reports

A “British man” has died after being beaten and set on fire by a mob in Ecuador, according to reports by media in the South American country.

According to reports, the man – who has not been officially identified – had been detained by police after being accused of being involved in a fatal shooting.

Ecuadorian news outlet Ecuavisa reported that the man had been taken to a police station Playas del Cuyabeno, a remote village in the Amazon rainforest.

While there, a group broke into the station and took the man away. He was then set on fire in the street, it is reported, and died from his burns.

Playas del Cuyabeno
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The incident reportedly happened in the Playas del Cuyabeno area of Sucumbios province

Another local report, from EXTRA.ec, said that specialist police units had been slow to arrive due to the geographical conditions of the area – which is accessible by river.

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According to reports, police officers at the station apparently decided they could not intervene when the mob arrived out of concerns for their own safety.

It is understood the UK Foreign Office is following up reports about the incident and working with local authorities to confirm the details.

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Environment

EcoFlow DELTA 3 Plus exclusive offer at $535, Hoverfly foldable e-bike $423, Anker 90K mAh power station $198, more

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EcoFlow DELTA 3 Plus exclusive offer at 5, Hoverfly foldable e-bike 3, Anker 90K mAh power station 8, more

We’re kicking off a new week here with a nice roundup of power station, e-bike, and other various markdowns in today’s edition of Green Deals. For starters, we’ve unpacked an exclusive offer on EcoFlow’s mid-range DELTA 3 Plus portable power station at $535, but you can also find the rather affordable Hoverfly foldable H3 e-bike as low as $423, and that’s alongside Anker’s SOLIX C300 AC 90,000mAh LiFePO4 power station at $198, but don’t sleep on that one because it expires at the end of the day.

Head below for more and, of course, Electrek’s best EV buying and leasing deals. Also, check out the new Electrek Tesla Shop for the best deals on Tesla accessories.

Exclusive: Here’s one of the best prices to date on EcoFlow’s mid-range DELTA 3 Plus portable power station at $535

We have secured an exclusive discount on the EcoFlow DELTA 3 Plus 1024Wh LiFePO4 Portable Power Station today for 9to5toys readers. Coming courtesy of the folks at Wellbots, using code 9TO5D3P at checkout will drop your total down to $534.65 shipped. Regularly listed at $799 directly from EcoFlow where it is currently marked down to $598, today’s deal delivers up to $264 in savings and the lowest price we can find.

For further comparison, this model is currently being sold for $699 on the EcoFlow Amazon storefront where the previous few deals had it sitting down at $616. We are also looking at a price drop that undercuts our previous exclusive discount from back in early February that had this model sitting down at $541.

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EcoFlow’s DELTA 3 Plus first landed on Amazon back in September 2024 to deliver a mid-range portable power supply ready to handle both emergency situations and the modest off-grid setup you might have planned for this summer.

Carrying a 1,024Wh LiFePO4, it features an 1800W AC output, 2200W (surge 3600W) with X-Boost alongside five methods of recharging (AC, Solar, 800W Alternator Charger, Smart Generator 3000 (Dual Fuel), Multicharging) and as many years of coverage on the included 5-year warranty.

For me these power stations have always been as much about peace of mind as they are useful on the campsite. Just knowing I’ve come some serious battery power at the ready just in case of the worse at home is equally as valuable to me as the portable power action, and more than worth the price of entry. With this in mind, this model in particular sits right in that sweet spot for me – enough to handle some tech out in the wild and more than enough to me through power outages and the like.

Amazon takes Hoverfly’s foldable H3 e-bike with up to 28-mile range down as low as $423 (Reg. $529)

Over at Amazon you can now find the Hoverfly H3 16-inch Folding Electric Bike in blue down at $423.20 shipped. You can also score the black colorway for $424.99. Typically priced at $529, you’re looking at as much as $106 off. This is a return to the price we saw late last month and comes within $23 of the all-time low we tracked back in January. It’s not hard to spend well over $1,000 or an electric bike, so this is an affordable way to take one for a spin this year. You can learn more about this model down below.

Folks who have been itching to pick up an e-bike, but cannot justify a premium model that’s often accompanied by a high price can now pick up Hoverfly H3 for a much more affordable cost. The brand touts that it “can travel 15.5 miles on pure electric” and nearly double that when switching to a pedal-assisted mode which ratchets that up “to more than 28 miles.” Speeds top out at 15.5 MPH and the 280.8Wh battery is removeable, allowing you to easily swap it out with a second battery if you want to go even further. My favorite feature here is that not only is the e-bike more compact than most, but that it also can be folded when not in use.

Today only: Grab Anker’s SOLIX C300 AC 90,000mAh LiFePO4 power station at $198 (Reg. $250)

As a part of its Deals of the Day sale, Best Buy is offering Anker’s SOLIX C300 AC 90,000mAh power station for $198 shipped. This is regularly a $250 power station which is now seeing a straight up $51 discount. We’ve seen this model fetch as low as $179 during Black Friday last year with our exclusive promotional discount, but it hasn’t been that low in quite a while. Today’s deal lands it within $9 of our previous mention from earlier this year, and it’s now fetching $2 less than Anker’s discounted price

Anker’s SOLIX C300 packs a hefty 90,000mAh LiFePO4 battery, delivering up to 600W of peak power (300W continuous), making it great for charging multiple devices and powering small appliances. Unlike the DC version that’s more USB-focused, the AC model featured here has three AC outlets, three USB-C ports, one USB-A port, and a 120W car/aux port. You can recharge the C300 in multiple ways – plug it into a wall to hit 80% under in under an hour, connect up to 100W of solar panels, charge via your car, or you can even use the PD 3.1 USB-C input. For added convenience, it includes a built-in carrying handle and a light bar above the display.

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