New resistance mechanism in the often multidrug resistant pathogen Acinetobacter baumannii

April 30, 2018, American Society for Microbiology

A team of Australian and Portuguese investigators has discovered yet another resistance mechanism in the pathogen, Acinetobacter baumannii, in this case, one that blocks the critical antibiotic-of-last-resort, colistin. A. baumannii is a highly troublesome pathogen globally, infecting primarily patients in intensive care units with ventilator-associated pneumonia, blood stream infections, and urinary tract infections. The research is published in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

The genesis of the research was the discovery by Portuguese clinicians that A. baumannii from a bloodstream remained in an elderly patient even after treatment. "Colistin was being used as a last-resort treatment as the strain was highly multidrug resistant," the patient having already been treated with six different antibiotics, said corresponding author John Boyce, PhD, BSc (Hons).

"The infection could not be cleared as the strain developed high-level colistin resistance during treatment," said Dr. Boyce, who is Associate Professor, Infection and Immunity Program, Monash Biomedicine Discovery Institute, and Department of Microbiology, Monash University, Melbourne, Australia. "The clinicians wanted to understand how the strain had become highly colistin resistant, so we determined whole genome sequences of the pre- and post-treatment isolates." (Dr. Boyce's conversations with these clinicians at a conference in Rome led to the collaboration on this research.)

The investigators then compared those sequences to identify the genetic changes associated with the acquisition of high-level colistin resistance. They found only one difference: a gene called hns had been disrupted by an insertion sequence element (a piece of DNA that can insert itself into a chromosome), preventing normal expression. The hns gene encodes a protein that regulates gene transcription. Disrupting such a transcription regulator would change expression of many other genes in the bacteria.

To determine how disruption of the regulatory gene, hns affected colistin resistance, the researchers compared transcription products of from pre- and post-treatment isolates. Expression of a gene that can boost colistin resistance had increased post-treatment.

Dr. Boyce and his collaborators performed several additional experiments that confirmed that the disruption of hns was responsible for the resistance, including inactivating hns in the non-resistant strain, which caused that strain to become "highly colistin resistant," said Dr. Boyce.

"Colistin is a 'last resort' antibiotic that is generally used to treat infections caused by bacteria that are resistant to all other antibiotics," said Dr. Boyce. "Development of colistin resistance in that are already multidrug resistant is incredibly alarming; the threat of pan-resistant infections is very real... development of high-level colistin resistance in this instance played a major role in treatment failure and led to an infection that could not be resolved (although the patient had other comorbidities)."

"Understanding the mechanisms behind development of resistance in clinical settings can allow us to identify treatments that minimize or circumvent , or will in future allow us to develop drugs that target the regulatory systems that control ," said Dr. Boyce.

Explore further: Even short travel can spread colistin-resistant bacteria

Related Stories

Even short travel can spread colistin-resistant bacteria

April 12, 2018
The emergence of antibiotic resistance among dangerous pathogens is increasingly problematic worldwide. Many strains of infectious bacteria have become multidrug-resistant, and cannot be treated with common antibiotic therapies. ...

Bacteria resistant to last-resort antibiotic, missed by standard tests

March 6, 2018
Emory microbiologists have detected "heteroresistance" to colistin, a last-resort antibiotic, in already highly resistant Klebsiella pneumoniae, a bacterium that causes blood, soft tissue and urinary tract infections.

Researchers discover novel colistin resistance gene mcr-3 in Escherichia coli

June 27, 2017
Researchers have now discovered a new mobile colistin resistance gene, mcr-3, in E. coli of pig origin. The novel mcr-3 gene was discovered when a colistin-resistant Escherichia coli isolate tested negative for both mcr-1 ...

First discovery in United States of colistin resistance in a human E. coli infection

May 26, 2016
The Multidrug Resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research (WRAIR) characterized a transferrable gene for colistin resistance in the United States that may herald ...

Recommended for you

More frequent checks control MRSA in newborns, but can hospitals afford them?

May 22, 2018
The more often a hospital can check its newborns for deadly MRSA germs, the more likely it will be that they are contained, according to a new study.

Could we predict the next Ebola outbreak by tracking the migratory patterns of bats?

May 22, 2018
Javier Buceta, associate professor of bioengineering, Paolo Bocchini, associate professor of civil and environmental engineering, and postdoctoral student Graziano Fiorillo of Lehigh University have created a modeling framework ...

Helping preterm infants grow bigger kidneys would prevent kidney disease later in life

May 21, 2018
Nephrons are the microscopic blood-filtering units inside our kidneys that convert waste products into urine, regulate our electrolyte levels and our blood pressure.

Kidney docs worry over no dialysis for undocumented immigrants

May 21, 2018
(HealthDay)—Undocumented immigrants in the United States are often denied treatment for kidney failure until they have a life-threatening emergency. Now a new study finds that the doctors and nurses who treat them are frustrated ...

Clues found to early lung transplant failure

May 21, 2018
Among organ transplant patients, those receiving new lungs face a higher rate of organ failure and death compared with people undergoing heart, kidney and liver transplants. One of the culprits is inflammation that damages ...

How to ethically conduct clinical research during public health emergencies

May 21, 2018
Following the 2014-2015 Ebola outbreak in West Africa, the U.S. National Academy of Sciences, Engineering and Medicine established a committee to assess the clinical trials conducted in Guinea, Sierra Leone and Liberia. In ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.