Researchers have discovered why a killer superbug is becoming more resistant to antibiotics. The findings open new doors to the development of potential treatments to fight the lethal infection that causes pneumonia and other diseases.
The study, “A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence,” was published in the journal EMBO Molecular Medicine.
Klebsiella is a gram-negative bacteria that can cause different types of healthcare-associated infections, including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis. Klebsiella bacteria have increasingly developed antimicrobial resistance, most recently to the class of antibiotics known as carbapenems, according to the Centers for Disease Control and Prevention (CDC).
Although found in the normal flora of the mouth, skin, and intestines, Klebsiella can cause destructive changes to human and animal lungs if inhaled — specifically to the alveoli in the lungs, resulting in bloody sputum.
In the new study, Jose Bengoechea, professor and director of the Centre for Experimental Medicine at Queen’s University Belfast and colleagues unveiled the molecular mechanisms preventing the treatment of Klebsiella pneumoniae.
Antibiotic resistance has often been associated with mutational inactivation of a gene called mgrB. According to the authors, “it is currently unknown whether mgrB mutation confers any loss of virulence. This is particularly critical given the increasing number of K. pneumoniae infections caused by virulent clones and the ease with which mgrB mutations arise in the hospital setting.”
Researchers found that mgrB inactivation leads to bacterial outer membrane modifications, which confer resistance to antibiotics and also to host defense peptides (which are produced by the body to help fight infections). Also, mgrB mutation substantially increased Klebsiella virulence.
“While it has been widely recognized that klebsiella is becoming resistant to the last line antibiotic, until now the precise underlying molecular explanation has not been understood,” Bengoechea said in a news release.
“Anti-microbial resistance is a global issue that will affect all of us. It touches on human, farmed animals and crop health, and so it is important that we remain cognizant of the interplay between humans, animals and the environments in which microbes live,” said Adam Staines, head of strategy for Agriculture and Food Security, The Biotechnology and Biological Sciences Research Council (BBSRC).
“Meeting this global challenge requires fundamental microbiological research such as this, through to close working with industry and policy makers, bringing together the research expertise and commitment of a broad range of disciplines,” he added.
The researchers also discovered that not only is Klebsiella becoming more resistant to antibiotics, it is also capable of increasing additional serious infections.
“Not only can we not treat or fight this infection efficiently, but it can cause severe infections by counteracting our body defenses, making it even more harmful than we had previously thought,” Bengoechea said. “The rate of resistance is unprecedented and coupled with the discovery that the microbe is provoking further infection, it is clear that a different approach is required.”
The discoveries should serve as a warning call.
“It’s crucial that hospital staff are informed of the potentially lethal effect of this infection and closely monitor patients, mindful that those affected by Klebsiella pneumoniae may endure further serious infections that may require different management,” Bengoechea said.
“This will go some way in mitigating the problem, but we are now working to find treatments against this type of infection, exploring the potential of boosting our own defenses so that we can find a long-term solution to avoid a potential pandemic in the future,” he concluded.
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