Bacterial Biofilms: The Hidden Fortress of Antibiotic Resistance

In the ongoing battle against bacterial infections, one of the most formidable adversaries
is not a single microorganism but a complex community known as a biofilm. These
microscopic fortresses, composed of bacteria encased in a self-produced protective
matrix, present a significant challenge to medical treatment and public health.
Understanding biofilms and their role in antibiotic resistance is crucial for developing
effective strategies to combat persistent infections.

What Are Bacterial Biofilms?

Biofilms are structured communities of bacteria adhering to surfaces and enveloped in a
self-secreted extracellular polymeric substance (EPS). This slimy matrix, composed of
polysaccharides, proteins, and DNA, protects the bacteria from external threats and helps

them adhere to both living tissues and inanimate objects. Biofilms can form on a variety
of surfaces, including medical devices (such as catheters and implants), human tissues
(like teeth and lungs), and natural environments (such as river rocks).

These biofilms cause chronic infections by exhibiting increased tolerance to antibiotics
and disinfectants, and by resisting the body’s defense mechanisms, including
phagocytosis. Persistent infections, such as those caused by staphylococci on medical
devices and Pseudomonas aeruginosa in the lungs of cystic fibrosis patients, are often due
to biofilm formation.[1]

The Formation of Biofilms

The development of a biofilm occurs in several stages:

Initial Attachment: Planktonic (free-swimming) bacteria attach to a surface
through weak, reversible interactions.
Irreversible Attachment: Bacteria firmly anchor themselves to the surface, often
using pili and other adhesive structures.
Maturation: The bacteria multiply and produce EPS, forming a complex,
three-dimensional structure.
Dispersion: Some bacteria break away from the biofilm to colonise new areas,
spreading the infection.

Free-floating, or planktonic, bacteria encounter a submerged surface and within minutes can become attached.
They begin to produce slimy extracellular polymeric substances (EPS) and to colonise the surface.
EPS production allows the emerging biofilm community to develop a complex, three-dimensional structure that is
influenced by a variety of environmental factors. Biofilm communities can develop within hours.
Biofilms can propagate through detachment of small or large clumps of cells, or by a type of “seeding dispersal”
that releases individual cells. Either type of detachment allows bacteria to attach to a surface or to a biofilm
downstream of the original community. [2]

Biofilms and Antibiotic Resistance

The role of biofilms in antimicrobial resistance (AMR) is highly complex and may
significantly drive resistance. Bacteria living in a biofilm can exhibit a 10 to 1,000-fold
increase in antibiotic resistance compared to similar bacteria living in a planktonic
state.[4]

For example, in a study examining antibiotic resistance of Staphylococcus epidermidis in
biofilms, 100% of isolates were susceptible to the antibiotic vancomycin when tested in a
planktonic state.[5] Still, nearly 75% of them were completely resistant to the same
antibiotic when tested from a biofilm. The same pattern has been seen for organisms like
Klebsiella pneumoniae, which appears to be susceptible when tested from an aqueous
solution but becomes highly resistant to certain antibiotics when tested from a biofilm.
This resistance arises from several factors:

1. Physical Barrier: The EPS matrix acts as a physical barrier, preventing antibiotics
from penetrating the biofilm fully and reaching all the bacteria within.

2. Slow Growth Rates: Bacteria in biofilms often grow more slowly than their
planktonic counterparts. Since many antibiotics target actively growing cells, they
are less effective against these dormant bacteria.

3. Efflux Pumps: Bacteria within biofilms can express efflux pumps, which actively
expel antibiotics from their cells, reducing drug efficacy.

4. Genetic Exchange: The close proximity of bacteria in a biofilm facilitates the
exchange of genetic material, including antibiotic-resistance genes, through
mechanisms such as conjugation.

Medical Implications

Bacterial biofilms significantly impact the management of over 75% of infections,
presenting challenges primarily through antimicrobial resistance, chronic infections,
immune response modulation, and medical device contamination. [7] Chronic infections,
such as those in diabetic wounds or cystic fibrosis, persist due to biofilm formation,
which creates a protective niche for microbes. Biofilms also modulate the host immune
response, sometimes causing harmful inflammation rather than protection.

Medical devices are particularly vulnerable to biofilm contamination, often leading to
persistent infections that may necessitate device removal. Despite increased research,
biofilms remain poorly understood, especially regarding treatment failures and the need
for novel antibiofilm therapies to improve clinical outcomes. This reveals the necessity

for future studies focused on biofilm-associated infections and innovative treatment
strategies.

Strategies to Combat Biofilms

Modern medicine is facing a microbial arms race, one which will require novel
approaches, beyond conventional antibiotic therapy, to win. Addressing the challenge of
biofilms requires innovative approaches:

Enhanced Antibiotic Formulations: Developing antibiotics that can penetrate the
EPS matrix or remain effective against slow-growing bacteria.

Anti-Biofilm Agents: Investigating substances that disrupt biofilm formation or
integrity, such as enzymes that degrade the EPS matrix or molecules that inhibit
bacterial adhesion.
Combination Therapies: Using a combination of antibiotics and anti-biofilm
agents to enhance treatment efficacy.
Surface Modifications: Designing medical devices with surfaces that resist
biofilm formation through materials science and engineering.
Quorum Sensing Inhibitors: Targeting the communication systems (quorum
sensing) that bacteria use to coordinate biofilm formation and maintenance.

Both public and private sector health entities must invest in advanced technologies and
provide specialised training for clinicians to effectively manage biofilm-associated
infections.

Conclusion

In the ongoing battle against bacterial infections, biofilms represent one of the most
formidable adversaries. These complex communities, challenge medical treatment and
public health by enhancing bacterial survival and promoting antibiotic resistance.
Understanding the formation, structure, and resistance mechanisms of biofilms is crucial
for developing effective strategies to combat these persistent infections as they
significantly impact infection management by fostering antimicrobial resistance,
sustaining chronic infections, modulating immune responses, and contaminating medical
devices.

Overcoming the challenge of biofilms requires innovative approaches, including
enhanced antibiotic formulations, anti-biofilm agents, combination therapies, and surface

modifications of medical devices. Both public and private sector health entities must
invest in advanced technologies and specialised training for clinicians to effectively
manage biofilm-associated infections. By addressing these microbial fortresses, we can
improve patient outcomes and tackle the growing threat of antibiotic-resistant infections.