A team of researchers and clinicians from Imperial College London have discovered a new mechanism by which bacteria can become antibiotic resistant. Even though this strain of bacteria has reduced fitness, the antibiotic treatments in hospitals enable these bacteria to thrive.
Antibiotic resistance is becoming an increasing problem, with growing numbers of people acquiring bacterial infections that are getting harder and harder to treat. One of the main causes of the increasing spread of antibiotic resistance is the misuse and overuse of the antibiotics themselves, and this study provides an explanation for why this is the case for a specific type of bacteria.
The team studiedKlebsiella pneumoniae, a bacterium that normally lives in the gut of many healthy people without causing any problems. However, ifKlebsiellagets into another part of the body, for instance when someone with infected hands touches an open wound, it can cause severe infections, including pneumonia, urinary tract infection, skin infection, blood infection, and meningitis.
“Antibiotics used to be very efficient in killingKlebsiella. However, in recent years we are facing the problem that many strains circulating in hospital settings are becoming more and more resistant to antibiotics,” explains team leader Gad Frankel.
His team studied the interaction ofKlebsiellawith a certain class of broad spectrum antibiotic called Carbapenems. These antibiotics tend to be used in hospitals when other treatments have failed. It was already known that these bacteria were able to resist the antibiotics by creating a specific type of enzyme inside the bacterial cell which could degrade the antibiotics and render them ineffective.
But the researchers found another mechanism that was at play as well. They discovered a genetic mutation that affects pores on the outer membrane of the bacterial cell. These pores are how the antibiotic molecules get into bacteria.
“A mutation in some strains ofKlebsiellanarrowed the diameter of the pores and, for that reason, the entry of the antibiotics is inhibited,” summarises Frankel.
The researchers compared the structures of the pores of the resistant bacteria to the pores of the non-resistant, or sensitive, bacteria, and found that two amino acids were inserted in the pore, which led to about a quarter reduction in its diameter. To verify that it was these two amino acids that caused the pore constriction, they used genetic engineering to insert the two amino acids in the appropriate place, and thus mutating a sensitive bacterium into an antibiotic resistant bacterium.
然而,随着smaller pore, it’s not only the antibiotics that cannot penetrate, but also some nutrients needed for growth. Which means that, by acquiring resistance to antibiotics in this way, the bacteria are less fit compared to typical bacteria.
In direct competition, the antibiotic resistant bacteria would lose to the sensitive bacteria. But in a hospital environment, antibiotics add selective pressure in favour of the resistant strains of bacteria.
“The use of antibiotics propagates the resistant bacteria, even though they have a disadvantage.”
What would be the way forward? We need to be more careful with our use of antibiotics, and, as Frankel points out, “we need to be able to define very early what antibiotic would be effective against a particular infection in a hospital setting, and therefore we will be able to use a narrow spectrum antibiotic, an antibiotic which will only kill the infecting organism.”
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