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Overcoming bacterial resistance: Using bioinspired engineering Nanomachine mechanism

Nanotechnology is an emerging field devoted to providing new insight into a vast range of subjects interfacing sciences and engineering. As advances in nanotechnology emerge continuously, new areas of applications in nanoscale communication also emerge that involve biological systems. By definition, nanocommunication is the exchange of information at nanoscale level and constitutes the basis of any wireless interconnection of individual nanomachines comprising a nanonetwork. Such systems have unique properties that must be taken into account, when trying to delve into new communication paradigms based on micro-biological communication systems. In this context, development of bio-inspired nanonetworks is a fledgling yet fast growing area of scientific interest with a significant impact on future applications in multiple fields (3).

One of the oldest nanomachines in biology is the bacterial flagellum. This apparatus is evolutionary essential, endowing onto bacteria the ability to move. The flagellum shares high similarity with another bacterial structure, the injectisome, which as the name implies is how some bacteria deliver their content to infect a host. A new study by researchers at Osaka University reveals how a specific structure in flagellum and injectisome, the export gate complex, dynamically assembles and how preventing this assembly could make bacteria innocuous. The study can be seen in PLOS Biology (4).

Multidrug resistance in pathogenic bacteria is an increasing problem in patient care and public health. Molecular nanomachines (MNMs) have the ability to open cell membranes using nanomechanical action (1). MNMs could be used as antibacterial agents by drilling into bacterial cell walls and increasing susceptibility of drug-resistant bacteria to recently ineffective antibiotics.

Scientists are one step closer to adapting the bacteria-killing power of a naturally occurring nanomachine, a tiny particle that performs a mechanical action.

In a study published in Nature (2), a UCLA-led team of researchers describe how the nanomachine recognizes and kills bacteria, and report that they have imaged it at atomic resolution. The scientists also engineered their own versions of the nanomachine, which enabled them to produce variations that behaved differently from the naturally occurring version.

Their efforts could eventually lead to the development of new types of antibiotics that are capable of homing in on specific species of microbes. Drugs tailored to kill only a certain species or strain of bacteria could offer numerous advantages over conventional antibiotics, including lowering the likelihood that bacteria will develop resistance. In addition, the tailored drugs could destroy harmful cells without wiping out beneficial bugs in the gut microbiome, and they could eventually offer the possibilities of being deployed to prevent bacterial infections, to kill pathogens in food and to engineer human microbiomes so that only favourable bacteria thrive.

The particle in the study, an R-type pyocin, is a protein complex released by the bacterium Pseudomonas aeruginosa as a way of sabotaging microbes that compete with it for resources. When a pyocin identifies a rival bacterium, it kills the bacterium by punching a hole in the cell's membrane. P. aeruginosa, frequently a cause of hospital-acquired illness, is found in soil, in water and on fresh produce. The germ is commonly studied and its biology is well understood.

Observing a pyocin's molecular structure—in its configurations both before and after that hole-punching—enabled the scientists to figure out the mechanisms by which it recognizes its prey and triggers its killing blow.

The research falls under the banner of a discipline called bioinspired engineering, which aims to develop technology that takes its design cues from nature. The results of the new study could contribute to the development of targeted antibiotics based on a pyocin.

Watch this video to see with your own eyes how it works ...