Drug-resistant bacteria behind deadly hospital-acquired infections shut out antibiotics by closing tiny doors in their cell walls. Scientists say the discovery could allow researchers to design drugs that “pick the locks” of these closed doors and allow antibiotics into bacterial cells. Klebsiella pneumoniae causes infections in the lungs, blood and wounds of those in hospitals, and patients that have compromised immune systems are especially vulnerable. More than 20,000 K. pneumoniae infections were recorded in UK hospitals in the past year. Like many bacteria, it is becoming increasingly resistant to antibiotics, particularly a family of drugs called Carbapenems. First author, Dr Joshua Wong, from the Department of Life Sciences at Imperial College London, said: “The prevalence of antibiotic resistance is increasing, so we are becoming more and more reliant on drugs like Carbapenems that work against a wide range of bacteria. “But now with important bacteria like K. pneumoniae gaining resistance to Carbapenems it’s important we understand how they are able to achieve this. “Our new study provides vital insights that could allow new strategies and drugs to be designed.” Carbapenems are used as antibiotics in hospitals when others have failed or are ineffective. Scientists say rising resistance to them could dramatically affect the ability to cure infections. In the study published in the Nature Communications journal, they looked at the structure of K. pneumoniae pores – the surface doorways through which antibiotics usually enter the bacteria. The team found that by shutting these doorways it becomes resistant to multiple drugs, since antibiotics cannot enter and kill them. But the closed doors also mean the bacteria can take in fewer nutrients, and tests in mice suggest that the bacteria grow slower as a result. However, the advantage in terms of avoiding antibiotics outweighed the negative impact of slower growth for the bacteria, allowing them to maintain a high level of infection, researchers say. The project was conducted in close collaboration with Dr Konstantinos Beis from the Department of Life Sciences, who is based at the Research Complex at Harwell in Oxfordshire. The team was led by Professor Gad Frankel, from the Department of Life Sciences at Imperial, who said: “The modification the bacteria use to avoid antibiotics is difficult to get around. “Any drugs to counteract this defence mechanism would likely also get blocked out by the closed doors. “However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provides information to help scientists and pharmaceutical companies make these new agents a reality.” Scientists say their results suggest the pressure posed by extensive use of Carbapenems in hospital settings is a major driver in the spread of these superbugs. They argue that there is a direct scientific basis for the implementation of restrictive prescribing policies that would minimise the use of broad-spectrum agents such as Carbapenems.