Study Targets Cause of Recurring Urinary Tract Infections
Millions of people have repeated urinary tract infections, despite the high-powered antibiotics of modern medicine. A new study suggests the reason why: A germ that invades the bladder builds a fort-like colony that resists both antibiotics and the body’s own immune system.
Researchers at Washington University in St. Louis used a powerful electron microscope to discover that pods of bacteria routinely form inside the cells lining the walls of the bladder in mice that have E. coli bacterial infections of the urinary tract.
The bacteria form a structure called a biofilm inside the cells, with thousands of individual bacteria becoming unified into a colony that resists attack, said Dr. Joseph J. Palermo, a Washington University researcher and the co-author of a study appearing in the journal Science.
“The bacteria rest in a matrix like eggs in a carton,” Palermo said. He said this is the first time that a biofilm structure has been found within a cell, and the discovery explains why many patients are unable to ever become completely free of urinary tract infections.
“In a biofilm, thousands and thousands of bacteria work together as sort of a multicellular organism,” said Gregory G. Anderson, a co-author of the study. He said the E. coli bacteria produce a polysaccharide film that inhibits antibodies and resists attacks from the immune system.
Anderson said the biofilm “is a slimy type of mesh” rather like the slick coating often found on submerged rocks in a stream or pool of water.
Palermo said the mouse is a commonly studied model for urinary tract disease because the tissue, cells and infection response of the rodent bladder are very similar to that of humans.
Dr. Josephine P. Briggs, head of group studying urinary tract disease at the National Institute of Diabetes and Kidney Research, one of the National Institutes of Health, said that the discovery of an E. coli biofilm is “very intriguing.” She said it explains why some bladder infections are so difficult to control in some patients.
“This study demonstrates this in mice, but there is no reason to think the process is not occurring in people,” Briggs said. “That needs to be documented, but it is very likely.”
If biofilm formation is confirmed in humans, she said, then it adds a new sense of urgency to the need to develop alternate ways to treat stubborn urinary tract infections.
The Washington University researchers said their studies show that individual E. coli bacteria assume different roles within the biofilm, acting like members of a multi-cell organism. Bacteria on the edge of the biofilm can burst out of the host cell and colonize other cells within the bladder wall.
Because the bacteria are within the cells of the bladder, they often are not detected by routine medical tests, Palermo said.
“When you check a urine sample for the presence of bacteria, all you are looking for are free-floating bacteria,” he said.
“If there are bacteria in the bladder tissue itself, you are not going to pick them up. Having sterile urine doesn’t really give you a picture of what the bacteria state of the bladder is. It makes diagnosis more difficult,” he said.
Recurring or highly resistant urinary tract infections are a major medical problem, particularly among women. The infections cause frequent and painful urination, fever and can lead to lead to more dangerous kidney infections.
About 8 million urinary tract infections are diagnosed annually, second only to respiratory infections in the United States. The urinary tract infections result in about 100,000 hospital admissions annually and treatment costs of about $1.6 billion. The E. coli bacteria cause about 80% of the infections.
It has been estimated that about half of all women will have at least one urinary tract infection during their lifetime and about 40% of these patients will have recurring infections.
