INTRINSIC ANTIBIOTIC RESISTANCE: A RESOURCE TO USE TO OUR ADVANTAGE

Antibiotic-resistant bacteria: there’s resistance (acquired) and resistance (intrinsic)!

Nowadays, antibiotic resistance is often cited as one of the major global threats to public health. The phenomenon of antimicrobial resistance (AMR) and, specifically, the resistance of pathogenic bacteria to antibiotics represent an urgent problem, as described in our dedicated deep dive (read here). This resistance is an acquired characteristic of bacteria, facilitated by indiscriminate use of antibiotics, which selects for resistant strains, allowing them to proliferate at the expense of sensitive ones.

However, it is crucial to distinguish between two types of resistance: acquired resistance and intrinsic resistance. While the former represents a concrete threat, the latter, in certain contexts, can become a valuable resource. In fact, leveraging intrinsic resistance in beneficial bacterial strains can help protect the microbiota and even reduce antibiotic consumption, thus decreasing the risk of further promoting the development of acquired resistance.

Intrinsic resistance in detail

Intrinsic resistance is a natural characteristic of some bacterial species, making them insensitive to specific antibiotics. This peculiarity is tied to the innate biological properties of the species and is not the result of mutations or genetic transfers. Unlike acquired resistance, it cannot be transferred to other bacteria and does not contribute to AMR.

For instance, intrinsic resistance can stem from:

• The absence of the antibiotic’s molecular target within the bacterial cell. In other words, if an antibiotic acts on a specific structure or function of the bacterium, such as cell wall synthesis, but the bacterium lacks that structure, the antibiotic becomes ineffective.
• A cell membrane impermeable to certain antibiotic molecules, preventing the drug from entering the bacterial cell to exert its function.

This form of resistance does not pose a public health risk when associated with beneficial bacteria such as probiotics. On the contrary, in these cases, it can become an important resource for protecting intestinal health.

Why can’t intrinsic resistance be transferred?

Intrinsic resistance is specific to certain bacterial strains and remains “isolated” and non-transferable, as bacterial strains with this characteristic lack plasmids, which could transfer resistance genes to other bacteria.

But what are plasmids? Plasmids are small, circular DNA molecules present in bacteria. They are separate from chromosomal DNA and contain accessory genes, such as those conferring antibiotic resistance. Unlike chromosomal DNA, plasmids can be transferred between bacteria using a connection bridge known as a pilus. This mechanism is one of the main drivers of the spread of acquired resistance.

We can imagine plasmids as a “USB stick” containing classified and illicit instructions that enable bacteria, including dangerous ones, to organize and resist antibiotic measures. Bacteria with intrinsic and non-transmissible resistance DO NOT possess any “USB stick” and, consequently, cannot spread information to evade antibiotic action.

Intrinsic resistance: so is it safe?

If a pathogenic bacterium has intrinsic resistance, it can pose a clinical challenge. The main difficulty lies in identifying the appropriate antibiotic to treat the infection, a process that may take longer and lead to more complex treatments.

Conversely, when this characteristic is present in beneficial bacteria, they behave as safe and respectful hosts that cause no disturbances.

It is important to specify, however, that antibiotic resistance in a probiotic strain must necessarily be specific, i.e., directed towards a single molecule or a specific class of antibiotic molecules. Strains with non-specific or broad-spectrum resistance conflict with safety regulations and are not marketable.

A successful example of intrinsic resistance to an antibiotic

A successful example of intrinsic resistance to an antibiotic, non-transferable, specific, and therefore safe, is Bifidobacterium breve PRL2020, contained in Brevicillin®. This strain has intrinsic resistance to amoxicillin and amoxicillin/clavulanic acid, whose safety profile has been confirmed by comprehensive genomic analysis. Moreover, the Bifidobacterium breve species is included in the EFSA (European Food Safety Authority) QPS (Qualified Presumption of Safety) list, meaning it is considered safe for human consumption due to its long history of use.

Additionally, the ability of Bifidobacterium breve PRL2020 to survive even during antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid allows it to act beneficially under the delicate conditions induced by the use of these antibiotics.

Brevicillin®: a safe and effective approach

The use of probiotics with intrinsic resistance represents an innovative opportunity to support gut health during antibiotic therapies. When a probiotic has specific and safe intrinsic resistance, as in the case of Brevicillin®, it becomes possible to use it alongside antibiotic therapy to safeguard the balance of our intestinal microbiota.

Brevicillin®, thanks to the presence of Bifidobacterium breve PRL2020, provides targeted support during therapies based on amoxicillin or amoxicillin/clavulanic acid. This strain, naturally resistant to these molecules, ensures several concrete benefits:

• Protection of the intestinal microbiota: Bifidobacterium breve PRL2020 survives even in the presence of antibiotics, continuing to perform its beneficial functions in the gut.
• Reduced risk of dysbiosis: The strain helps maintain microbiota biodiversity, limiting microbial alterations and side effects such as diarrhea, bloating, or intestinal discomfort.
• Prevention of opportunistic bacterial overgrowth: By preserving intestinal balance, Brevicillin® counters the overgrowth of pathogenic microorganisms that can cause secondary infections.
• Support for post-therapy recovery: By ensuring a more stable microbiota during therapy, it promotes a faster and more complete recovery of intestinal flora at the end of treatment.

Thanks to these properties, Brevicillin® is a fundamental ally for tackling antibiotic therapies with amoxicillin or amoxicillin/clavulanic acid more safely and effectively. Its ability to protect the microbiota also helps reduce the need for further therapeutic interventions, favoring a preventive and integrated approach.

In summary, the use of a probiotic like Brevicillin® during antibiotic therapy is an innovation combining safety, efficacy, and intestinal health protection. Moreover, it contributes to the global fight against AMR, as promoting reduced antibiotic use decreases the selective pressure exerted by these drugs on the bacteria inhabiting our bodies.