Bacterial fibers critical to human, avian infection

February 4, 2014

Escherichia coli – a friendly and ubiquitous bacterial resident in the guts of humans and other animals – may occasionally colonize regions outside the intestines. There, it can have serious consequences for health, some of them lethal. 

In a new study conducted in assistant professor Melha Mellata’s lab in the Biodesign Institute at Arizona State University, lead author Alyssa K. Stacy and her colleagues examine one such bacterial adversary, Avian pathogenic Escherichia coli (APEC).  Download Full Image

The research, conducted in collaboration with scientists at the University of Florida, Gainesville, appears in the current issue of the journal PLOS ONE

The researchers targeted a specific group of threadlike fibers known as E. coli common pilus (ECP), which adorn bacterial cell surfaces. In the first study of its kind, they analyzed the way these structures contribute to APEC’s ability to cause infection and form dense cell aggregates known as biofilms. 

APEC infections are a serious threat to poultry, causing both systemic and localized infections, collectively known as colibacillosis. These afflictions cause significant economic losses to the poultry industry, due to the costs of treatment for infected birds, lowered rates of egg production and mortality. 

Further, APEC infections may pose a risk to humans, due to their zoonotic potential – their ability to infect human hosts. A better understanding of infectious capacity (or virulence) and zoonotic potential are therefore essential for combatting these hazardous pathogens. 

Stacy was an undergraduate student in Mellata’s lab, and was partially supported by funding from School of Life Sciences Undergraduate Research (SOLUR), ASU. She was joined by Biodesign researchers Natalie M. Mitchell, Jacob T. Maddux and Roy Curtiss III, director  of the institute’s Center for Infectious Diseases and Vaccinology and professor in the College of Liberal Arts and Sciences.

Avian Pathogenic E. coli belong to a broad group of extraintestinal pathogenic E. coli (ExPEC) strains. Colibacillosis, caused by APEC in birds, leads to serious illness, often attacking the avian respiratory system, producing systemic or localized infections depending on the age and gender of bird, immunologic health and various environmental factors.

Because APEC and human ExPEC forms share important virulence characteristics, possible zoonotic transmission is a serious health concern. APEC may also provide a reservoir for virulence genes that may be acquired by human strains. 

Many types of bacteria produce extracellular surface fibers like ECP, enabling them to adhere to one another, as well as to various surfaces. But such fibers – or pili – perform other vital functions, particularly in the case of pathogenic bacteria. Pili, including those projecting from the surfaces of E. coli, are capable of recognizing specific host cell receptors during their initial phase of colonization. 

Bacteria make further use of their pili to form cellular biofilms. Such bacterial aggregates are of clinical importance, as they provide reservoirs for pathogenic organisms to persist in the host, and often display increased resistance to antibiotics. 

E. coli common pilus was originally identified in an ExPEC form known to cause neonatal meningitis in humans, but was later recognized as a component in all classes of E. coli – both pathogenic and benign.

While E. coli bacteria exist primarily as beneficial residents of the human intestine, extraintestinal variants are responsible for diarrheal diseases like hemorrhagic colitis, as well as urinary tract infections, neonatal meningitis, sepsis and pneumonia. The toll of such diseases – particularly in the developing world – is substantial, claiming some 2.5 million lives per year. Most of these victims are children. 

The current study draws on examinations of ECP, both in vitro and in vivo. The aim was to determine the prevalence of ECP among APEC strains and evaluate its contribution in the early stage of biofilm formation and host-cell recognition. Additionally, the study assessed ECP’s role in virulence in baby chicks. 

The new research demonstrates – for the first time – the prevalence of ecpA, a gene coding for a major structural subunit of ECP in a majority APEC sequences examined. (The complex architecture of ECP fibers is composed of six distinct structural subunits.) With the aid of PCR methods, the group tested 167 APEC strains derived from chickens and turkeys afflicted with colibacillosis, 76 percent of which tested positive for ecpA (which was previousely associated with human pathogenic E. coli). 

The authors stress that the results confirm that APEC and human pathogenic E. coli strains share virulence traits. They further speculate that ecpA may permit the persistence of E. coli bacteria in the intestine, where they exist in a non-threatening state, before migrating to alternate, extraintestinal sites and becoming pathogenic. 

Environmental conditions, including low pH, low growth temperature and high acetate concentration have been shown to upregulate the expression of ECP in human E. coli strains that cause urinary tract infections, meningitis and diarrheal diseases. In the current study, an APEC strain was found to adhere to human cervical cells in a manner similar to human ExPEC infections. Further, the results showed that adorning APEC with anti-ECP antibodies – a process known as opsonization – could significantly inhibit bacterial adherence. This finding suggests that ECP could be considered  as a potential antigen for vaccines for both human and poultry infections.

The formation of biofilms is a common bacterial property, including in E. coli, where the adaptation increases survivability inside and outside of the host, and provides an ideal environment for the exchange of genetic material. Bacteria forming biofilms frequently display antibiotic resistance, and can be tenacious foes to combat medically. Deletion of ECP-related genes was shown to reduce biofilm production.

Finally, the study attempted to evaluate APEC virulence in baby chicks, using strains with deleted ECP genes. Results show a reduction in virulence. In fact, the potential for colonization among the ECP deletion strains was reduced, particularly in the bloodstream. 

The new work demonstrates multiple roles for ECP in APEC, and thus presents a plausible target for future therapeutics aimed at these serious infections of both humans and animals. 

“Our study has clearly shown that although the gene of ECP was found in a large number of APEC, these bacteria express this gene differently when they are in contact with cells or in biofilm,” Mellata says. “Elucidating how the expression of some genes is turned on or off by different factors will help us understand how these bacteria cause disease."

Richard Harth

Science writer, Biodesign Institute at ASU


New gift supports actuarial science at ASU

February 4, 2014

The School of Mathematical and Statistical Sciences at Arizona State University has received a gift provided by Blue Cross Blue Shield of Arizona to support the school’s new actuarial science program.

The Phoenix-based insurance company has established the Blue Cross Blue Shield of Arizona Actuarial Science Scholarship. The company contributed $30,000 to endow the scholarship to support a School of Mathematical and Statistical Sciences student specializing in actuarial science. Download Full Image

The scholarship is the first at the School of Mathematical and Statistical Sciences that specifically benefits actuarial science majors. The school’s new actuarial science program, which is accepting students for fall 2014, will train qualified graduates to earn professional actuarial credentials, thus enhancing the workforce for insurance companies and other organizations. ASU offers the only undergraduate actuarial degree program in Arizona, and one of only a few such programs in the inter-mountain west.

Housed at the School of Mathematical and Statistical Sciences, the bachelor of science in actuarial science program was established to give students a strong background in mathematics, statistics and business. Students must pass a series of exams to become certified actuaries. The first several exams can and should be attempted during their undergraduate studies. The remaining exams can be completed while on the job.

“We’re proud to establish this scholarship in support of the School of Mathematical and Statistical Sciences and its students,” said Sandy Gibson, executive vice president and former chief actuary at Blue Cross Blue Shield of Arizona, who began her actuarial science career at ASU. A member of the new ASU Actuarial Advisory Board, Gibson added, “By providing support for the students in this new actuarial science degree at ASU, we are investing in the development and growth of the next generation of actuaries.”

Al Boggess, director of the school, said the gift “will help qualified undergraduates pursue this new degree which will prepare them for one of the most lucrative careers in the country. I sincerely thank Blue Cross Blue Shield of Arizona for their generosity.”

The first Blue Cross Blue Shield of Arizona Actuarial Science Scholarship of $1,000 will be awarded this fall to a full-time undergraduate actuarial science student at the junior or senior level. Recipients will be known as the Blue Cross Blue Shield of Arizona Actuarial Scholars.

Blue Cross Blue Shield of Arizona, an independent licensee of the Blue Cross and Blue Shield Association, is the largest Arizona-based health insurance company. The not-for-profit company was founded in 1939 and provides health insurance products, services or networks to more than 1.2 million individuals.

The School of Mathematical and Statistical Sciences is an academic unit in the College of Liberal Arts and Sciences. 

Rhonda Olson

Manager of Marketing and Communication, School of Mathematical and Statistical Sciences