A study by the Institute of Integrative Systems Biology (I2SysBio), located in the scientific-business area of the UV Science Park and joint centre of the Higher Council for Scientific Research (CSIC) and the University of Valencia (UV), shows that Escherichia coli bacteria, which inhabit the human intestine and are highly relevant to health, grow predictably following the laws of physics after having been exposed to antibiotics. The results, published in the journal Nature Communications, highlight the role of mechanical forces and cell geometry in bacterial division processes, and open up new ways to understand microbial behaviour and develop more effective antibiotic treatments.
During stress situations such as those caused by exposure to antibiotics, bacteria can disrupt their cell division and start growing in the form of filaments. It is a mechanism of bacterial resistance known as 'filamentación', frequent in infections such as those of the urinary tract. This growth generates mechanical stresses that bend and deform the filaments. The study, led by I2SysBio researcher Javier Buceta, shows that these bacteria tend to curve in a predictable way according to the laws of physics. "This behaviour is not random, it responds to a studied mechanics which regulates how stress is distributed in the cell as it grows," explains the PCUV researcher.
The work focuses on antibiotic-induced filament formation and demonstrates, for the first time in filamentous bacteria such as E. coli, that this curvature does not only affect the external structure of the cell (its shape), but also modifies key biological processes for their survival and behaviour. For example, the change in cell shape alters the activity of a protein network called Min, which 'scans' the cell to determine the correct site of division.
"This phenomenon, which links the biological response with mechanical behaviour, is related to transport phenomena within the cell, since curvature modifies how proteins move and cluster in the cell membrane. This is the first demonstration of a mecano-biological effect on filamentous bacteria", Javier Buceta, I2SysBio researcher
Using a multidisciplinary approach, the study shows that in areas of higher curvature there is a lower concentration of DNA and MinD protein, as well as increased activity of the cell division machinery. "This phenomenon, which links the biological response with mechanical behaviour, is related to transport phenomena within the cell, since curvature modifies how proteins move and cluster in the cell membrane. This is the first demonstration of a mecano-biological effect on filamentous bacteria," says Buceta.
In this sense, the work shows that, once the stress disappears, the cell tends to divide at the points of maximum curvature, indicating that it retains an 'imprint' of the stresses suffered. This 'mechanical memory' acts as an internal marker that guides future divisions when conditions return to be favourable.
On the implications of these findings, Marta Nadal, PhD student and first author of the article, argues that "this mecano-biological perspective opens up new lines of research in biomedicine, where therapies that interfere with their physical or structural properties could be explored".
"In addition, understanding how bacteria retain 'memory' of adverse situations can be crucial to anticipate their behavior after antibiotic treatments, helping to prevent relapse or resistance. In the field of public health, this knowledge could be applied to the design of strategies for the control of persistent or recurrent infections, especially in a context of growing antibiotic resistance," says Nadal.
"Understanding how bacteria retain 'memory' of adverse situations can be crucial in anticipating their behaviour after antibiotic treatments, helping to prevent relapse or resistance. In public health, this knowledge could be applied to the design of strategies for the control of persistent or recurrent infections, especially in a context of growing antibiotic resistance", Marta Nadal, PhD student at I2SysBio and first author of the article
"Our work goes beyond traditional biochemical mechanisms and reveals that physics is a fundamental director in its division," says Iago López Grobas, postdoctoral researcher 'Marie Curie' in the group and co-director of research. "In essence, we bring a new piece to the puzzle: the physical form of the bacterium is not a simple consequence of its growth, but an active signal that guides its fate. This is crucial for understanding how bacteria divide effectively even under adverse conditions, a knowledge that can be exploited to develop strategies that disrupt this process and overcome resistance», he adds.
"We are intrigued to explore whether other physical stimuli in the environment, such as electric fields or other mechanical forces, can also induce similar alterations and 'memories' in the process of division. The goal is to create a complete map of how bacteria integrate the physical signals in their environment to make cellular decisions, opening the door to new strategies for fighting infections," concludes López Grobas.
Filamenting is a key survival mechanism for bacteria when they begin to form 'biofilms', structured communities of bacteria that adhere to surfaces and have a negative impact on multiple sectors such as health or the food industry. "Understanding how cellular mechanics determines the shape and behaviour of filaments could be used to design more effective materials for preventing or controlling the formation of biofilms," says Buceta. "For example, to make catheters with structural properties that interfere with bacterial filamentación and can locally destabilize the incipient biofilms," he concludes.
Source: Delegation CSIC Comunitat Valenciana