How flesh-eating bacteria attack the body's immune system

August 14, 2008

"Flesh-eating" or "Strep" bacteria are able to survive and spread in the body by degrading a key immune defense molecule, according to researchers at the University of California, San Diego, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. The finding, which could aid in development of new treatments for serious infections in human patients, will be reported in the August 14 issue of the journal Cell Host & Microbe.

Led by senior author Victor Nizet, M.D., UC San Diego professor of pediatrics and pharmacy and an infectious diseases physician at Rady Children's Hospital, San Diego, the researchers showed that a protease known as SpyCEP (Strep. pyogenes cell envelope protease) - produced in large amounts by the most dangerous strains of Strep -inactivates an immune system molecule that controls the body's white blood cells ability to fight bacteria. Without signals from this molecule, white blood cells become slower and weaker, and infections can spread out of control.

"These findings may suggest a new approach to treating serious Strep infections by supporting our body's natural defense system," said Nizet.

The research focuses on the major human pathogen group A Streptococcus. Among the most important of all bacterial pathogens, Strep is responsible for a wide range of diseases - from simple strep throat to life-threatening conditions such as necrotizing fasciitis ("flesh-eating disease") and toxic shock syndrome.

The UC San Diego investigators examined the interaction of Strep bacteria with neutrophils, specialized white blood cells that play a front-line role in humans' immune defense against pathogenic microbes. Previous research had shown that Strep bacteria change their pattern of gene expression dramatically during the course of infection, including a massive increase in production of SpyCEP, which has the unique ability to inactivate an immune defense molecule known as interleukin-8 (IL-8). IL-8 is produced at sites of infection and serves as a signal for neutrophils to migrate out of the bloodstream and into the tissues to clear the infection.

The UC San Diego team used a molecular genetic approach for their studies, knocking out the gene encoding the SpyCEP from a pathogenic strep strain that was originally isolated from a patient suffering from necrotizing fasciitis.

"Lacking this single protease, the mutant Strep strain was easily killed by human neutrophils," said lead author Annelies Zinkernagel, M.D., a postgraduate researcher in the UCSD department of pediatrics. "In addition, the mutant Strep bacteria no longer produced a spreading infection when injected into the skin of experimental mice."

The critical role of the Strep protease was confirmed by cloning the corresponding gene into a normally non-pathogenic bacterial strain, which then became resistant to neutrophil killing. More detailed analysis demonstrated that by inactivating IL-8, SpyCEP blocked neutrophil migration across blood vessels as well as neutrophil production of "extracellular traps" used to ensnare bacteria.

The immune-blocking effects of SpyCEP produced by Strep were strong enough to allow other bacterial species to survive at the site of infection, which may contribute to mixed infections that require complex antibiotic regimens. The researchers also showed that a pathogen of fish, Streptococcus iniae, produces its own version of SpyCEP that may contribute to recent reports of severe skin infections caused by this bacterium in fish handlers.

Nizet explained that the researchers' findings could lead to novel treatments for Strep-related diseases. "In addition to attempting to kill the bacteria directly with standard antibiotics, new treatment strategies could be targeted to inhibit the Strep protease and thereby disarm the pathogen, making it susceptible to clearance by our normal immune defenses," he said.

University of California - San Diego

---

---

	Bacteria: Staph, Strep, Clostridium, and Other Bacteria (Class of Their Own) by Judy Wearing (Author)
	Surviving MRSA: Learn How to Protect Yourself by Dr Joseph Parazoo (Author) This is a tale of a vicious disease that has a preference for human flesh, and an appetite that surpasses the worst of nightmares. However, this is not a Hollywood horror movie. This one is made by Mother Nature, and is very, very real..... This is a story of one such real case. Learn how this near death experience changed there lives forever...... for the better. Warning! This book contains Graphic Pictures.
	Streptococcal Infections: Clinical Aspects, Microbiology, and Molecular Pathogenesis by Dennis L. Stevens (Editor), Edward L. Kaplan (Editor) Streptococcal Infections: Clinical Aspects, Microbiology, and Molecular Pathogenesis offers an in-depth examination of the spectrum of hemolytic streptococcal infections and their complications. Additionally, the volume incorporates and discusses aspects of pneumococcal, entrococcal, and oral streptococcal disease. The recent resurgence of rheumatic fever, concomitant outbreaks of severe systemic group A streptococcal infections (often accompanied by toxic shock), an increasing incidence of multiple antibiotic resistance among streptococcal species, and an intensified effort to develop effective streptococcal vaccines have brought renewed attention to the continuing role of streptococci for causing significant medical and public health problems in both industrialized and developing...
	A Field Guide to Germs, Revised and Updated Edition by Wayne Biddle (Author) From the ravages of the Ebola virus in Zaire to outbreaks of pneumonic plague in India and drug-resistant TB in New York City, contagious diseases are fighting back against once-unconquerable modern medicine. Public concern about infectious disease is on the rise as newspapers trumpet the arrivals of new germs and the reemergence of old ones. In A Field Guide to Germs, Pulitzer Prize-winning science writer Wayne Biddle brings readers face to face with nearly one hundred of the best-known (in terms of prevalence, power, historical importance, or even literary interest) of the myriad pathogens that live in and around the human population. Along with physical descriptions of the organisms and the afflictions they cause, the author provides folklore, philosophy, history, and such...
	The Woman with a Worm in Her Head: And Other True Stories of Infectious Disease by Pamela Nagami (Author), F. Gonzalez-Crussi (Foreword) A normal, healthy woman becomes host to a pork tapeworm that is burrowing into her brain and disabling her motor abilities. A handsome man contracts Chicken Pox and ends up looking like the victim of a third degree burn. A vigorous young athlete is bitten by an insect and becomes a target for flesh-eating strep. Even the most innocuous everyday activities such as eating a salad for lunch, getting bitten by an insect, and swimming in the sea bring human beings into contact with dangerous, often deadly microorganisms. In The Woman with a Worm in Her Head, Dr. Pamela Nagami reveals-through real-life cases-the sobering facts about some of the world's most horrific diseases: the warning signs, the consequences, treatments, and most compellingly, what it feels like to...
	Help! Whats Eating My Flesh?: Runaway Staph and Strep Infections! (24/7: Science Behind the Scenes: Medical Files) by Thomasine E. Lewis Tilden (Author) Medical Files examines the science and technology behind some of the most fascinating medical cases and mysteries, from flesh-eating diseases to deadly mosquito bites, and more.
	Biotechnology of Lactic Acid Bacteria: Novel Applications by Fernanda Mozzi PhD (Editor), Rául R. Raya (Editor), Graciela M. Vignolo PhD (Editor) This title represents a broad review of current research on LAB and their novel applications with contributions from a number of well-known leading scientists. The book encompasses a wide range of topics including both traditional and novel developing fields, and provides unparalleled, comprehensive information on new advances of genomics, proteomics, metabolism and biodiversity of LAB. Chapters contain state-of-the-art discussions of specific LAB applications such as their use as probiotics, live vaccines and starter cultures in old and new fermented products. The safety of these microorganisms and their interactions with diverse ecosystems natural biota are also covered as well as the new applications of well-known (bacteriocins) and novel (vitamins, low-calorie sugars, etc.)...
	Baby 411: Clear Answers & Smart Advice For Your Baby's First Year by Denise Fields (Author), Ari Brown M.D. (Author) You are having a baby! Congratulations! Now, the reality hits you—what the heck am I doing?  What if you could bottle the wisdom of all those parents who’ve come before you . . . and mix it with the solid medical advice from an nationally-renowned pediatrician? Baby 411 is the answer! Think of it as the ultimate FAQ for new parents. Inside you’ll learn:     • How to pick a pediatrician with savvy questions to ask and insider tips.     • Sleep. The best way to get your baby to sleep through the night.     • First aid—when to worry, when not . . . and what to do when baby gets sick. No-nonsense, down-to-earth advice you can trust.     • Fussy baby 411. Is it colic? Acid reflux? Or something else? Discover  the secrets to soothing a fussy baby.       ...
	Genetics of Lactic Acid Bacteria (The Lactic Acid Bacteria) by B.J. Wood (Editor), Philip J. Warner (Editor) Beginning with an introduction to relevant genetic techniques, chapters cover all major groups of LAB, including the Bifidobacteria; plasmid biology, gene transfer, phage, and sugar metabolism; gene expression of various LAB; applications for genetically engineered LAB, including the emerging field of medical applications; and the legal and consumer issues that arise from such applications. This resource will set the benchmark for the state of knowledge of LAB genetics and should be of value to food scientists and other researchers working with LAB in its present and future capacities. Professionals using lactic acid bacteria (LAB) for research and/or as working organisms, whether in food and dairy fermentations or in the exciting new field of clinical delivery agents, will find this book...
	Toddler 411: Clear Answers & Smart Advice For Your Toddler by Denise Fields (Author), Ari Brown M.D. (Author) You’ve made it! Your baby has turned one! Now the real fun begins. From temper tantrums to toilet training, raising a toddler brings its own set of challenges and questions — and Toddler 411 has the answers. Following on the heels of the best-seller Baby 411, Toddler 411 bottles the wisdom of parents who’ve “been there, done that” . . . and combines it with solid medical advice from an award-winning pediatrician. Inside, you’ll learn: •    The truth about The Terrible Twos—and how to raise a well-behaved child without going insane.  •    Picky Eaters—learn how to cope . . . and convince your child to eat something besides Goldfish crackers.  •    Toilet train your toddler in just one day. No, that’s not a typo—learn the Zen of...