Breaking News
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Newly identified subset of immune cells may be key to fighting chronic inflammation
January 19, 2019 - New immune response regulators discovered
January 18, 2019 - Poor blood oxygenation during sleep predicts chance of heart-related death
January 18, 2019 - First international consensus on the diagnosis and management of fibromuscular dysplasia
January 18, 2019 - Rapid resistance gene sequencing technology can hasten identification of antibiotic-resistant bacteria
January 18, 2019 - Researchers develop artificial enzymatic pathway for synthesizing isoprenoids in E. coli
January 18, 2019 - Scientists advise caution in immunotherapy research
January 18, 2019 - How children across the world develop language
January 18, 2019 - Columbia Medical Student Receives McDonogh Scholarship
January 18, 2019 - Secretive ‘Rebate Trap’ Keeps Generic Drugs For Diabetes And Other Ills Out Of Reach
January 18, 2019 - Plant based diet could be the best option for the planet says commission
January 18, 2019 - New conservation practice could reduce nitrogen from agricultural drainage, study shows
January 18, 2019 - UIC researchers receive $1.7 million NCI grant to study Southeast Asian fruit
January 18, 2019 - New study determines the fate of DNA derived from genetically modified food
January 18, 2019 - Scientists develop new gene therapy that prevents axon destruction in mice
January 18, 2019 - Study finds critically low HPV vaccination rates among younger adolescents in the U.S.
January 18, 2019 - Brain cells involved in memory play key role in reducing future eating behavior
January 18, 2019 - Risk for Conversion of MS Varies With Different Therapies
January 18, 2019 - Investigational cream may help patients with inflammatory skin disease
January 18, 2019 - Medical school news office receives six writing awards | News Center
January 18, 2019 - County By County, Researchers Link Opioid Deaths To Drugmakers’ Marketing
January 18, 2019 - Research reveals risk for developing more than one mental health disorder
January 18, 2019 - Scientists discover a dramatic pattern of bone growth in female mice
January 18, 2019 - Study finds link between lengthy periods of undisturbed maternal sleep and stillbirths
January 18, 2019 - New nuclear medicine method could improve detection of primary and metastatic melanoma
January 18, 2019 - Combination therapy shows high efficacy in treating people with leishmaniasis and HIV
January 18, 2019 - Health Tip: Don’t Ignore Changes in Skin Color
January 18, 2019 - Dietary Recommendations for Healthy Children
January 18, 2019 - Eliminating the latent reservoir of HIV
January 18, 2019 - Pain From The Government Shutdown Spreads. This Time It’s Food Stamps
January 18, 2019 - Newly discovered regulatory mechanism helps control fat metabolism
January 18, 2019 - New rapid blood tests could speed up TB diagnosis, save the NHS money
January 18, 2019 - Researchers develop intelligent system for ‘tuning’ powered prosthetic knees
January 18, 2019 - Monoclonal antibody pembrolizumab prolongs survival in patients with squamous cell carcinoma
January 18, 2019 - New research detects mosquito known to transmit malaria for the first time in Ethiopia
January 18, 2019 - Researchers identify new genes linked to development of age-related macular degeneration
January 18, 2019 - Computerized method helps better protect pharma patents
January 18, 2019 - New guidelines to make swallowing safer for people in Australian nursing homes
January 18, 2019 - Lumex Instruments’ RA-915AM monitor installed at Hg treatment plant in Almadén, Spain
January 18, 2019 - ACCC survey finds multiple threats to growth of cancer programs
January 18, 2019 - Meeting the challenge of engaging men in HIV prevention and treatment
January 18, 2019 - Furloughed Feds’ Health Coverage Intact, But Shutdown Still Complicates Things
January 18, 2019 - Experts discuss various aspects on health risks posed by fumigated containers
January 18, 2019 - Researchers use gene-editing tool CRISPR/Cas9 to limit impact of parasitic diseases
January 18, 2019 - Alpha neurofeedback training could be a means of enhancing learning success
January 18, 2019 - Innovative ‘light’ method demonstrates positive results in fight against malignant tumors
January 18, 2019 - The cytoskeleton of neurons found to play role in Alzheimer’s disease
January 18, 2019 - New resource-based approach to improve HIV care in low- and middle-income countries
January 18, 2019 - Bedfont appoints Dr Jafar Jafari as first member of the Gastrolyzer Medical Advisory Board
January 18, 2019 - New study shows link between secondhand smoke and cardiac arrhythmia
January 18, 2019 - DZIF scientists reveal problems with available diagnostics for Zika and chikungunya virus
January 18, 2019 - Breast cancers more likely to metastasize in young women within 10 years of giving birth
January 18, 2019 - Over 5.6 million Americans exposed to high nitrate levels in drinking water
January 18, 2019 - Blood vessels can now be created perfectly in a petri dish
January 18, 2019 - Study identifies prominent socioeconomic and racial disparities in health behavior in Indiana
January 18, 2019 - Young-Onset Type 2 Diabetes Tied to Increased Hospitalization Risk
January 18, 2019 - For-profit nursing schools associated with lower performance on nurse licensure test
January 18, 2019 - Considering the culture of consent in medicine
One type of Chlamydia protein manipulates human cells in two different ways

One type of Chlamydia protein manipulates human cells in two different ways

image_pdfDownload PDFimage_print

When Chlamydia trachomatis, the bacterium that causes one of the most common sexually transmitted infections worldwide, infects a human cell, it hijacks parts of the host to build protective layers around itself.

Inside this makeshift fortress, the bug grows and reproduces, eventually bursting out in search of a new target and killing the host cell. While scientists have known for years that Chlamydia protects itself in this way, they were missing the mechanics until now.

Researchers from Duke University and the MRC Laboratory of Molecular Biology in Cambridge, UK, have shown that one Chlamydia protein, known as ChlaDUB1, is capable of manipulating human cells in two different ways, at least one of which appears to be essential for thriving inside its host.

The findings which appeared this week in Nature Microbiology could pave the way for treating Chlamydia with fewer antibiotics.

Structural biologists led by David Komander of the MRC Laboratory of Molecular Biology and Chlamydia experts at Duke University collaborated on the study. Initially, Komander and postdoctoral fellow Jonathan Pruneda, now an assistant professor at Oregon Health & Science University, contacted Duke Professor Raphael Valdivia, Vice Dean for Basic Science, to discuss the ChlaDUB1 protein, which Valdivia’s team had worked on before.

ChlaDUB1 is one of a class of proteins generated by Chlamydia to disrupt host cell function. Komander, Pruneda, and colleagues found that the protein is an enzyme, a deubiquitinase, that removes ubiquitin, a small protein that human cells attach to other proteins to activate them or to indicate that those proteins should be torn up. Human cells use ubiquitin to send signals, many of which are important for inflammatory responses to pathogens like Chlamydia.

Komander’s group determined through further study of the ChlaDUB1 enzyme’s shape that it can also modify proteins with acetylation to disrupt the alarms human cells raise to fight infection.

“Instead of making two proteins, one that has the deubiquitinase activity and a separate one that has acetylation activity, they’ve combined that into the same protein,” said coauthor Robert Bastidas, a research assistant professor who is part of Valdivia’s group at Duke.

Chlamydia is unlike other bacteria in that it can’t survive on its own outside of a human cell, Bastidas explained. He said it is likely that the bug has cast off large parts of its genome in order to better survive inside host cells. He hypothesizes that the bacterium saves space with this mashed-together protein, the only Chlamydia protein that has been found to have these two functions.

While it was clear that ChlaDUB1 was capable of both functions, Bastidas and his colleagues at Duke wanted to know what the enzyme was doing inside its host during Chlamydia infection. The researchers infected human cells with wildtype Chlamydia, as well as with mutant strains harboring defective copies of ChlaDUB1.

Once Chlamydia has built its fortress within the host cell, it breaks up the host cell’s Golgi apparatus and maneuvers the pieces around itself. The Golgi apparatus is a cellular compartment that typically stays close to the nucleus of the cell and modifies proteins by adding sugars that serve as baggage tags indicating whether the proteins should go to the plasma membrane or to some other cellular compartment. It’s not clear why the bacterium surrounds itself with pieces of the Golgi, perhaps to use the sugars and fats for its own growth, but it’s the only bacterium known to do so.

In the scientists’ infection trials, the wildtype Chlamydia chopped up the Golgi as usual. But when infected with a bug carrying a mutant enzyme, the human cells’ Golgi remained intact, suggesting that ChlaDUB1’s activity is necessary for this aspect of Chlamydia infection.

Bastidas also hypothesizes that the ability for ChlaDUB1 to remove ubiquitin from host proteins protects Chlamydia from the host inflammatory response.

Next, the researchers want to find a drug that will specifically disrupt the function of ChlaDUB1, thus slowing the bacteria’s ability to fight off attack by the host immune system. “If we develop these inhibitors and they’re specific enough, then we won’t have to use antibiotics” or at least use fewer of them, said Bastidas.

In a world where antibiotic use can lead to antibiotic resistance or to disruption of the delicate microbiome of the vagina and the urinary tract, where Chlamydia prefers to reside, Bastidas says a more tailored therapy could prove a better tool to fight infection.

Tagged with:

About author

Related Articles