11:19pm Monday 21 October 2019

Groundbreaking Discovery by AGH Researchers Shows Rapid Evolution of Bacterial Genomes Over the Course of a Single Chronic Infection

Researchers from the Center for Genomic Sciences at Allegheny General Hospital (AGH) in Pittsburgh have made a landmark discovery about the evolutionary nature of bacteria in the setting of chronic infectious disease. Reporting today in the journal PLoS Pathogens, the AGH team documents for the first time that bacteria engage in a process called horizontal gene transfer to evolve rapidly during the course of a single infection.

The result is a group of highly-related bacterial strains that are changing genetically so fast that it is likely nearly impossible for the host’s immune system to effectively track and eradicate it, said Garth Ehrlich, PhD, scientific director of the Center for Genomic Sciences and the paper’s senior author.

“Much like we see with other successful pathogens, such as viruses and certain parasitic organisms, which are designed to mutate and confuse the immune system, bacteria – which cause the vast majority of chronic infectious disease in the United States – appear to be using a similar tactic. And they are doing so through a dynamic, real-time process of altering their genetic code that until now has not been understood and which is counter to conventional wisdom about the typical pace of species evolution,” Dr. Ehrlich said.

From a patient and public health perspective, the discovery could have significant implications, according to Christopher Post, MD, PhD, a pediatric ear, nose and throat specialist, medical director of the AGH Center for Genomic Sciences and president of the Allegheny Singer Research Institute.

“Bacterial infections are some of the most formidable and costly diseases that healthcare professionals confront on a daily basis in clinics and hospitals throughout the world. This finding may prove to be a seminal event in our pursuit of more effective strategies for overcoming the primary challenges to preventing and treating such infections, including antibiotic resistance, chronic biofilm disease and bacterial species that readily adapt to vaccinations,” Dr. Post said.

Bacterial infections have traditionally been studied under the assumption that a single genetic organism is at the heart of any single case of infection. Over the past decade, Dr. Ehrlich, Dr. Post and others at the Center for Genomic Sciences have helped pioneer the concept that many chronic infections do not fit this paradigm, but rather are the result of multiple strains or species of bacteria living together in highly structured and formidable communities, called biofilms.

In the course of studying biofilms, the AGH team began documenting evidence that bacteria often incorporate DNA from neighboring bacteria into their own genomes. Called horizontal gene transfer, the process leads to the evolution of new bacterial strains.

Using advanced high throughput bacterial DNA sequencing, Dr. Ehrlich and his colleagues in the current study investigated the tempo and relevance of horizontal gene transfer among nasopharyngeal strains of Streptococcus pneumoniae recovered from a child with chronic respiratory and middle ear infections. Specimens were collected during the child’s clinic visits over a seven month period.*

Commonly referred to as pneumococcus, Streptococcus pneumoniae is one of the world’s most prevalent and deadly pathogens, associated with severe invasive diseases such as meningitis and bacteremia as well as common mucosal diseases such as pneumonia, sinusitis and otitis media.

Complete genome sequencing and comparative genomics were performed by the AGH team on multiple bacterial strains collected during the course of the child’s pneumococcal infection.

“We identified extensive gene transfer among multiple infecting strains of the bacteria. Comparing the original strain that started the infection with strains sequenced at its end, approximately 7.5% of the entire genome had changed. In just a seven month period of time, we documented a remarkable ongoing evolution of this species that appears to be precisely orchestrated to confound the host’s immune surveillance,” Dr. Ehrlich said.

The immune system works in a similar fashion, Dr. Ehrlich said, by continuously realigning the genomes of white blood cells so they can recognize and destroy foreign pathogens.

“It is essentially a genomic chess match where bacteria, through horizontal gene transfer, are always staying one step ahead,” Dr. Ehrlich said.

As its next step, the AGH team plans to conduct a broader analysis of HGT activity across multiple species of bacteria.

“Once we have verified that horizontal gene transfer is indeed a common occurrence in chronic bacterial infections, and we expect that to be the case, it opens the door to a realm of promising new directions in the study and treatment of these diseases,” Dr. Ehrlich said.

In addition to Drs. Ehrlich and Post, other key members of the Center for Genomic Sciences staff who contributed to the PLoS Pathogens paper included Fen Z. Hu, Luisa Hiller, and Azad Ahmed. 


Editor’s Note: * Specimens for the case study documented in the PLoS Pathogens paper were obtained from a child participating in a separate study at Children’s Hospital of Pittsburgh, as part of a collaborative agreement between Children’s Hospital and AGH.     **PLoS Pathogens is now the world’s leading and most cited infectious disease journal.

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