mBiosphere

Understanding How Gonorrhea Spreads: It's Seminal

The sexually transmitted infection gonorrhea has been around for centuries, described in early writings from Egypt, China and Japan. Even the bible describes warnings about “unclean discharges from the body.” Yet although the bacteria behind the infection, Neisseria gonorrhoeae, were first identified back in 1879, there are still many questions that remain unanswered about how these organisms spread from person to person.

A study in mBio this week offers clues. Researchers at Northwestern University’s Feinberg School of Medicine in Chicago and the University of Cologne in Germany have found that exposure to seminal plasma – the liquid part of semen containing secretions from the male genital tract – allows N. gonorrhoeae to more easily move and start to colonize in human tissues.

In a series of laboratory experiments, the investigators found that 24 times as much N. gonorrhoeae could pass through a synthetic barrier after being exposed to seminal plasma. In addition, exposure to seminal plasma caused hairlike appendages on the bacteria surface, called pili, to move the cells by a process known as twitching motility. This stimulatory effect could be seen even at low concentrations of seminal plasma and beyond the initial influx of seminal fluid.

Additional tests found that exposure to seminal plasma enhanced the formation of bacterial microcolonies on human epithelial cells (cells that line body cavities), which can also promote the establishment of infection.

“Our study illustrates an aspect of biology that was previously unknown,” said lead author study Mark Anderson of Northwestern. “If seminal fluid facilitates motility, it could help transmit gonorrhea from person to person.”

A photomicrograph of Neisseria gonorrhoeae viewed using a Gram-stain technique. Credit: Centers for Disease Control and Prevention

Today gonorrhea is the second most common sexually transmitted infection in the U.S., according to the Centers for Disease Control and Prevention, with estimates upward of 800,000 new cases each year. Fewer than half are diagnosed and reported. Untreated, gonorrhea can lead to serious and permanent health problems, including pelvic inflammatory disease in women and epididymitis, a painful condition of the testicles that may lead to infertility, in men. Untreated gonorrhea also increases a person’s risk of acquiring or transmitting HIV.

With more than 100 million estimated new cases of gonorrhea annually worldwide, said senior study author H. Steven Seifert of Northwestern, “research characterizing the mechanisms of pathogenesis and transmission of N. gonorrhoeae is important for developing new prevention strategies, since antibiotic resistance of the organism is becoming increasingly prevalent.”

Antibiotics once effective against gonorrhea, including penicillin, tetracycline and fluoroquinolones, are no longer recommended because of high rates of resistance. Only one class of antibiotics, cephalosporins including the oral antibiotic cefixime, has been left to treat the disease. But more recently, evidence from CDC’s Gonococcal Isolate Surveillance Project (GISP) suggests that cefixime, too, is becoming less effective. New gonorrhea treatment guidelines published in 2012 suggest only injectable ceftriaxone be used in combination with one of two oral antibiotics, either azithromycin or doxycycline. 

 

-Karen Blum

An effective disinfectant for tuberculosis found on the grocery store shelf: Vinegar kills mycobacteria

Vinegar has been used as a disinfectant for thousands of years, but new evidence shows that it might also be an inexpensive and effective way to fight the spread of tuberculosis (TB) and other mycobacterial infections. 

A colony of Mycobacterium abscessus expresses the red fluorescent protein dtTomato while growing in vivo in an infected zebrafish. Image credit: Audrey Bernut

A new study in mBio this week shows that not only does acetic acid, the active ingredient in vinegar, kill Mycobacterium tuberculosis, but it also kills members of the Mycobacterium abscessus complex, a group of emerging mycobacterial culprits, which can be both antibiotic-resistant and disinfectant-resistant.

“Mycobacteria are known to cause tuberculosis and leprosy, but non-TB mycobacteria are common in the environment, even in tap water, and are resistant to commonly used disinfectants. When they contaminate the sites of surgery or cosmetic procedures, they cause serious infections and can leave deforming scars,” says Howard Takiff, senior author on the study and head of the Laboratory of Molecular Genetics at the Venezuelan Institute of Scientific Investigation (IVIC) in Caracas.  These non-TB mycobacteria were behind one of Brazil’s largest outbreaks of post-surgical infections in 2007.

The most effective disinfectants against TB are chlorine bleach, which is toxic and highly corrosive, or commercial disinfectants that can be very expensive. In the resource-poor countries where the majority of TB occurs, Takiff notes, there is a great need for effective, non-toxic, non-corrosive and inexpensive disinfectants.

Vinegar, which fits all of those requirements, has been used as a cleaning agent and medical remedy since ancient times. Recommended for soothing jellyfish stings and treating swimmer’s ear, it is also used widely used to wash produce. Takiff’s postdoctoral fellow, Claudia Cortesia, rediscovered the disinfecting power of acetic acid during a routine experimental control.

Cortesia was investigating drugs that might block the resistance of M. abscessus to commonly used disinfectants. One such drug needed to be dissolved in acetic acid, but when she ran the negative control for the experiment by simply adding the acetic acid solvent to the bacterial culture, she realized that it alone was killing off the pesky M. abscessus.

“This was one of those ‘Huh?’ moments in science,” says Takiff.  “Is this an artifact or do we pursue this? Claudia is an unassuming, modest, hard-working and talented scientist. She has this habit of making interesting, unexpected observations and then we work to explain them.”

While on a sabbatical in Laurent Kremer’s lab at University of Montpellier 2 in France, Takiff had the chance to confirm how effective acetic acid was against M. abscessus, “perhaps the most resistant and pathogenic of the non-TB mycobacteria and a frequent cause of infections,” he says. He often stopped at the grocery store on his way to the lab and picked up a liter of white vinegar for less than US$1 for his experiments. He found that mixing the cultures with a 10% acetic acid solution for 30 minutes effectively killed the bacteria, including complex members M. abscessus, M. bolletii, and M. massiliense.

Since neither the Kremer nor the Takiff laboratory was equipped to test TB strains, their collaborators Catherine Vilchèze and William Jacobs, Jr. at the Albert Einstein College of Medicine in New York tested acetic acid’s ability to kill M. tuberculosis strains that were virulent, multidrug resistant (MDR), and extensively drug resistant (XDR). For all three strains, 30 minutes exposure to a solution of 6% acetic acid killed the bacteria, with no survivors remaining.

A 10% acetic acid solution is about twice as strong as vinegar sold in US grocery stores, and the authors calculate that enough acetic acid to disinfect 20 liters worth of TB samples or cultures would cost less than US$100. Takiff notes that even a 25% solution is non-toxic and only a mild irritant if spilled on the skin.

Although the team did not investigate the mechanism of action of acetic acid’s ability to kill mycobacteria, they did show that it is not simply due to the low pH of the solution. Takiff says that the lack of any resistant bacteria to it suggests a generic mechanism, rather than something that depends on one or two specific genes in a pathway.

“We can’t say we discovered something since vinegar’s ability to disinfect has been known since the Roman ages. Two thousand years of uses can’t be all wrong,” says Takiff. “It turns out the disinfectant activity of acetic acid was investigated in the early 20^th century and has been studied in the food industry. We observed this interesting effect and extended earlier findings to suggest that vinegar might be worthwhile reconsidering to see if it’s practical and useful in the lab, and maybe even the clinic.”

--Kendall Powell

Camels harbor coronavirus causing Middle East Respiratory Syndrome

Camels are an essential source of labor, transportation and food for millions of people in the Middle East, Africa and Asia. But at least in Saudi Arabia they also may harbor a dangerous coronavirus, according to a study in mBio this week.

The study, a comprehensive survey of dromedary camels throughout Saudi Arabia, found the virus causing Middle East Respiratory Syndrome (MERS), called MERS-CoV, in camels throughout the country. Adult camels were more likely to have antibodies to the virus while juveniles were more likely to have active virus, hinting that infection in camels occurs early in their lives, and if people get the virus from camels it is most likely from contact with young camels, said the researchers, directed by Ian W. Lipkin of Columbia University, New York. In addition, antibodies to the virus were observed in archived camel blood serum dating back to 1992.

Dromedary Camel. Image credit: iStockphoto.

MERS is a serious viral respiratory illness that has been identified in 182 people since 2012, 79 of whom have died from the condition. While most infections have occurred in Saudi Arabia, the origin of disease, in most cases, has remained unknown.

As often happens in science, finding the link to camels was somewhat incidental. In 2012 Saudi Arabia’s Deputy Minister of Health, Ziad Memish, asked Lipkin’s team to help identify an animal source of MERS after the infection was identified in the first victim, an elderly man who had died. Suspecting bats, the team made news headlines last year after reporting they had found a virus in an Egyptian Tomb Bat genetically identical to the one found in the man; the bat was just a few miles from the man’s home. During their sleuthing, the team noted that the man had four pet camels, and “we were struck by that,” Lipkin says. So they collected a dozen or so blood samples from camels, and from some cows and sheep, too.

But bringing the samples back to the United States for analysis proved challenging, Lipkin says, because of concerns about spreading foot-and-mouth disease. Arriving home at New York’s John F. Kennedy Airport, Lipkin’s team found their samples held up by customs, while a series of government agencies including the Department of Homeland Security and the Department of Agriculture became involved. Eventually, says Lipkin, the samples were transported by special hazard truck to the National Biodefense Analysis and Countermeasures Center in Frederick, Md., where they were tested for foot-and-mouth disease. After the samples were cleared, the special hazard truck returned them to New York.

To avoid such snafus during the current study, Lipkin’s colleague Thomas Briese and associates brought a mobile laboratory to Saudi Arabia, where they worked side by side with Abdulaziz Alagaili, Osama Mohammed, and Iyad Zalmout of King Saud University and the Saudi Wildlife Authority in Riyadh testing camel blood samples and swabs from camels’ noses and rectums, and analyzing archived camel serum samples from as early as 1992.

They found that 74 percent of camels sampled countrywide had antibodies to MERS-CoV. More than 80% of adult camels throughout the country had antibodies to the virus, while in camels age two or younger the prevalence ranged from 90% in the eastern part of the country to 5% in the southwest.

Active virus was most frequently detected in nasal swabs, in 35% of young camels and 15% of adult camels countrywide, but less frequently in rectal swabs and not in blood, indicating that the virus most likely is spread by respiratory secretions. 

---by Karen Blum

Canine Distemper Virus Threatens India's Tiger Population

In an mBio article published in August, scientists showed that canine distemper virus (CDV) has infected and caused fatal neurological disease in endangered Amur tigers.  CBS News recently reported that India is challenged in finding ways to protect its tiger population from this disease.  Wild tigers in India are already at risk because of poaching and reduction in dwelling space.  This disease will pose an additional threat to the tiger population.  

Related links:

Canine Distemper Virus: an Emerging Disease in Wild Endangered Amur Tigers (Panthera tigris altaica) (mBio Research Article)

Canine Distemper Virus (CDV) in Another Big Cat: Should CDV Be Renamed Carnivore Distemper Virus? (mBio Commentary article)

Canine distemper an emerging disease in rare Amur tigers, poses "significant risk to survival" (mBiosphere)

India scrambles to save tigers from deadly virus (CBS News)