Conditional pathogenic bacteria known as Klebsiella belong to the family Enterobacteriaceae and are considered part of the normal intestinal flora in healthy individuals. These straight, gram-negative rods typically form capsules, are generally non-motile, and thrive on simple nutrient media.
However, some species of Klebsiella are among the most common pathogens responsible for pneumonia, intestinal and urogenital infections in patients with weakened immune systems. In 2017, experts from the World Health Organization classified Klebsiella as one of the most dangerous bacterial pathogens due to their increasing resistance to antimicrobial agents.
Recently, a research team led by Trevor Lithgow collected samples from the Vuruntieri water reservoirs and discovered two subtypes of the bacteriophage Merri-merri-uth nyilam marra-natj (MMNM), which infects the bacterium Klebsiella pneumoniae.
Although both subtypes were nearly identical, one of them, designated as MMNM (Ala134), exhibited reduced activity against the multidrug-resistant strain of Klebsiella AJ174-2 (multidrug-resistant bacteria are those that have developed resistance to two or more antibiotics).
This slight difference formed the basis for further experiments aimed at studying the evolution of phages. In particular, scientists conducted a series of experiments exposing the phage MMNM (Ala134) to the multidrug-resistant strain of Klebsiella AJ174-2, which causes pneumonia.
As a result, researchers obtained 20 new variants of the phage with various phenotypic expressions.
Further genome sequencing of the new variants helped identify mutations in a small set of proteins that make up the viral base plate, which plays a crucial role in the process of infecting bacteria. Since thin, long threads extend from the base plate, aiding phages in attaching to bacteria, even minor changes in its structure can impact the efficiency of infection.
It is important to note that, unlike antibacterial agents that eliminate both pathogenic organisms and members of the normal flora, phages are more selective and target specific species of microorganisms, helping maintain the microflora's defense against infection. Previously, it was believed that phages primarily evolve through large genetic rearrangements, such as gene recombination, leading to mosaicism— the presence of genetically distinct cells.
However, the results of a new study, published in the journal mBio, demonstrated that even small point mutations can lead to evolutionary changes, allowing bacteriophages to quickly adapt to new hosts and environmental conditions.
“All the phages we developed can kill Klebsiella, but some variants do it better than others,” noted the authors of the scientific work.
Understanding the evolutionary and adaptive mechanisms of phages is crucial for developing new methods to combat infections resistant to modern antibiotics. This discovery offers hope for the existence of yet-unknown natural populations of phages with genetic variations capable of destroying superbugs. The work also broadens our understanding of microevolutionary processes and is significant for studying the genetic diversity of viral populations.