Designing Bacterial Mutants: From Gene Editing to Robust Strain Engineering

À la surface de notre peau et au cœur des follicules pilo-sébacés vit une bactérie bien connue : Cutibacterium acnes. Particulièrement abondante dans les zones riches en sébum, cette bactérie à Gram positif et anaérobie aérotolérante est fréquemment associée à l’acné.

Pourtant, sa présence n’est pas en elle-même le signe d’un déséquilibre. C. acnes fait partie du microbiote cutané normal et se retrouve aussi bien sur une peau saine que sur une peau à tendance acnéique. Certaines études ont même montré que son abondance globale pouvait être relativement comparable dans ces deux situations.

Le rôle de C. acnes ne peut donc pas être compris en recherchant uniquement sa présence ou en mesurant sa quantité. Il dépend également de la composition de sa population, des propriétés des souches qui la constituent et de leurs interactions avec leur environnement.

Why can an antibiotic active against several Gram-negative bacteria lose much of its efficacy against Pseudomonas aeruginosa?

A study published in 2026 in Microbiology Spectrum, to which Smaltis contributed, provides new insights into this question. It shows that the MexXY(OprM) efflux pump plays a major role in the resistance of P. aeruginosa to odilorhabdins, a new class of antibiotics targeting the bacterial ribosome.

Beyond this finding, the study illustrates an essential reality in the development of new antimicrobials: knowing a compound’s target is not enough. It is also necessary to understand how the bacterium detects it, adapts to it, and organises its defence

In microbiology, a strain is never just another component of a protocol. It carries a genome, a history and an origin that determine what an experiment can truly reveal. Two strains belonging to the same species can therefore generate different results, all technically valid, yet not necessarily answering the same scientific question.

This is why, at Smaltis, strain selection is an integral part of experimental design. Before searching a collection or looking for a specific isolate, we first clarify the objective of the project: is the aim to standardize a method, understand a mechanism, evaluate an antimicrobial compound, reproduce a resistance phenotype, or represent a clinical situation? The answer then determines the most appropriate model: a reference strain, a human, veterinary or environmental isolate, a strain panel, an available mutant, or a custom-built strain.

Once upon a time, there was a scent so familiar that it was given its own name: petrichor.
It is the unmistakable fragrance that rises from the ground after the first drops of a summer rain fall onto dry soil. A comforting, almost universal scent that evokes woodland walks, gardens after a thunderstorm, or cherished childhood memories.
For centuries, people simply believed it was the smell of wet earth. The truth, however, proved far more fascinating.

Microbiological contamination is not limited to a non-compliant result. In R&D development, quality control, an industrial process or biological production, it immediately raises concrete questions: where does the contaminant come from, is it isolated or recurrent, what is its impact, and how can its reappearance be prevented?

The response is not simply to identify the bacterium and then restart the process. To achieve lasting control of bacterial contamination, the investigation must be able to connect laboratory observations with the real operational context: samples, flows, raw materials, equipment, cleaning, disinfection and field practices.

At Smaltis, we approach these situations as a structured microbiological investigation: understanding the problem, isolating the contaminants, identifying and comparing the isolates, preserving useful material, and then testing appropriate prevention solutions.

The skin microbiome is not mere scenery. It is a functional component of the skin, involved in protection against pathogens, immune dialogue, and the modulation of inflammation. It is a dynamic ecosystem shaped by subtle interactions between bacteria, yeasts, the host, and the environment.

Our approach is grounded in a simple conviction: understanding a microbiome is not merely about identifying it. It is about knowing how to culture it, interrogate it, and generate scientifically defensible data.

This is precisely how we approach the skin microbiome: as a complex ecosystem whose actors, dynamics, and mechanisms must be mastered before attempting to modulate its balance.

Once upon a time, in the hospitals of the twenty-first century, there was an infection that even antibiotics could no longer silence. An opportunistic infection caused by a bacterium called Clostridioides difficile, it often appeared in patients who were already vulnerable… and, above all, already heavily treated. Let us look back at the history of this infection, which gave rise to new therapeutic approaches.

Probiotics are often presented as a simple category. In reality, their characterization has become a demanding scientific and regulatory exercise. It is no longer enough to identify a species or to invoke a favorable history of use: the demonstration must now be conducted at the strain level, in a way that is consistent with the intended use, the target population, and the applicable regulatory framework. In the main reference frameworks, a microorganism can be qualified as a probiotic in the strict sense only if it is sufficiently characterized, safe for its intended use, alive at a relevant dose until the end of the product’s shelf life, and associated with a documented health benefit. [1,5,7,8]

The key question therefore becomes: what can we robustly demonstrate about its identity, safety, and functional activity? This is particularly true for new or poorly documented strains, for which taxonomy alone is not sufficient. The EFSA, GRAS, and Canadian frameworks converge on one central point: useful characterization is strain-level characterization interpreted in light of the final use. [1-6]

The construction of bacterial mutants is a cornerstone of microbiology. Historically used to decipher gene function, it now plays an equally strategic role in bioproduction, biotechnology, and the development of therapeutic bacteria, where the engineered strain itself may ultimately become the final product.

This shift has profoundly changed how mutagenesis projects are approached. Today, the objective is no longer simply to modify a gene, but to design a strain aligned with its final application, operational constraints, and regulatory expectations.

Once upon a time, an invisible battle was raging deep inside our noses. A microscopic battlefield, where bacteria fought relentlessly to defend their territory. Picture a small village of indomitable Gauls, surrounded on all sides… but instead of Romans, it’s microbes. And in this surprisingly strategic setting, a most unexpected antibiotic was discovered: lugdunin.