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Novel Insights into Infections

Urinary tract infections (UTIs) account for more than 7 million office visits a year in the United States alone. They are responsible for over a million emergency room visits and 100,000 hospitalizations. Patients typically visit their doctor because of the pelvic pain associated with having a UTI.  Although little is known about how symptoms result from infection, it is widely assumed that infection-induced inflammation causes pain.

However, Dr. David Klumpp, PhD, and his team recently published studies in the Journal of Infectious Diseases which offer surprising insights into bacterial infection and the basis of infection-associated pelvic pain. These studies focused on two strains of E. coli, NU14 and 83972, which were originally isolated from patients’ bladders.  Since NU14 was from a UTI patient and 83972 was from a patient with asymptomatic bacteria in the bladder, Dr. Klumpp’s group used these E. coli strains to determine what bacterial features drive pelvic pain.

When the NU14 strain was put into mice via a catheter, mice developed UTIs and had pelvic pain. However, when 83972 was introduced into mice, the mice were pain free.  Surprisingly, the pelvic pain was not correlated with how many NU14 were in the bladder.  Inflammation was also not the determinant of pain because both E. coli strains caused similar levels of bladder inflammation.  Examining molecules found on the surface of E. coli led the team to lipopolysaccharide (LPS), a notorious molecule long known for stimulating strong inflammatory responses, including toxic shock.

Dr. Klumpp’s team purified LPS from NU14 and 83972 and found the purified LPSs caused the pelvic pain or the absence of pain just like the intact bacteria – even though both LPSs caused the same level of inflammation.  Finally, the LPS from 83972 was able to reduce the normal UTI pain levels of NU14 bacteria.

These studies are beginning to change how we think about infection.  Because 83972 LPS reduced pain, it suggests bacteria have evolved to influence interactions between microbes and bacteria.  Dr. Klumpp speculates that bacteria have evolved modifications of their surfaces to promote (or disguise) symptoms that might promote spreading, such as coughing.

Most importantly, Dr. Klumpp thinks these surface molecules can be harnessed for therapies.  For example, other studies from the Klumpp lab show that bladder pain can be reduced via the gut through neural connectivity called “organ crosstalk.”  Dr. Klumpp envisions exploiting pain-suppressing molecules like 83972 LPS to provide relief of bladder symptoms by engineering 83972-like features onto harmless bacteria of the gut.