Mycoplasma Biofilm: Formation, Disease, and Resistance

A mycoplasma biofilm is a structured community of Mycoplasma bacteria, which are unique for their lack of a cell wall. These bacteria embed themselves in a self-produced, protective matrix, adhering to surfaces within a host. This formation allows the bacteria to act as a cooperative unit, enhancing their survival. These biofilms establish resilient, long-term infections that are difficult for the host’s immune system and antibiotic therapies to eliminate.

Formation and Composition

A mycoplasma biofilm has two primary components: the Mycoplasma bacteria and the extracellular polymeric substance (EPS) they produce. Mycoplasma are the smallest known self-replicating organisms and are resistant to antibiotics that target cell wall synthesis. The EPS matrix is a complex, sticky web that encases the bacteria, holding the cells together in a structured community. This matrix is composed of polysaccharides, proteins, lipids, and extracellular DNA.

Formation begins when individual, free-floating Mycoplasma cells attach to a surface, such as the lining of the respiratory tract. Once attached, the bacteria colonize the area by multiplying and forming small, dense clusters known as microcolonies, which can be observed within 48 hours.

As the community grows, it produces more of the EPS matrix, which envelops the microcolonies and merges them into a larger, three-dimensional structure. The mature biofilm develops into highly differentiated structures, sometimes featuring tower-like formations and channels for nutrient exchange. This developmental process, from initial attachment to a mature community, can take several days to weeks depending on the species and conditions.

Association with Chronic Disease

Mycoplasma biofilms are linked to chronic, persistent infections because their structure allows them to establish a long-term presence in the host. They are found in the respiratory and urogenital tracts, where they contribute to diseases that are difficult to resolve. By shielding the embedded organisms, these biofilms are a primary reason the associated diseases become chronic.

In the respiratory system, Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia, with infections noted for being recurrent and resistant to treatment. The biofilm’s persistence can lead to chronic inflammation in the airways, contributing to chronic bronchitis and potentially exacerbating conditions like asthma. Research indicates that during asthma flare-ups, patients show signs of mycoplasma infections.

In the urogenital tract, Mycoplasma genitalium is a known cause of non-gonococcal urethritis, cervicitis, and pelvic inflammatory disease. These conditions are characterized by their chronicity and resistance to multiple drugs. The persistent presence of these bacterial communities can trigger ongoing inflammation and tissue damage, leading to stubborn symptoms.

Mechanisms of Persistence and Resistance

The resilience of mycoplasma biofilms is due to several survival mechanisms. The first is the physical barrier created by the EPS matrix. This dense enclosure obstructs the penetration of antibiotics, preventing them from reaching the bacteria inside in effective concentrations. Bacteria within a biofilm can be 10 to 1,000 times more resistant to antibiotics than their free-floating counterparts.

Bacteria in the deeper layers of a biofilm undergo metabolic changes due to limited access to nutrients and oxygen. These inner bacteria enter a slow-growing or dormant state. Many antibiotics are most effective against actively dividing bacteria, so these slowed-down “persister cells” can survive treatment. They can then repopulate the biofilm after the antibiotic course ends.

The biofilm structure also helps evade the host’s immune system. The EPS matrix can mask bacterial antigens, which are molecules that immune cells like phagocytes would recognize to trigger an attack. This camouflage prevents the immune system from mounting an effective response to clear the infection. The persistent, low-level presence of the biofilm may lead to chronic inflammation, allowing the bacteria to persist for long periods.