# Biofilm Formation as a Complex Result of Virulence and Adaptive Responses of _Helicobacter pylori_
## 1 The Issue of Biofilm Formation in the Biomedical Sector  
Despite their small sizes, microorganisms are characterized by exceptional complexity and diversity [1]. Classically, microorganisms can appear as free-swimming (planktonic) forms or multicellular clusters, referred to as biofilms [2; 3; 4; 5; 6]. Microbial biofilm is defined as a structured consortium of cells immersed in a self-produced matrix [2; 6]. It is worth mentioning, however, that the biofilm may also include host components, e.g., fibrin, antibodies, platelets, or leukocytes. Biofilms can be attached to an abiotic or biotic surface, but they can also constitute a mobile, non-adhered structure floating in culture broth or body fluids [2; 3]. Because of the proximity of microbial cells and their physical, metabolic, and social interactions, the biofilm growth differs significantly from the planktonic lifestyle [2; 3; 4; 5]. Probably, the first observer of biofilms was [PERSON] (1632-1723), who, using a primitively constructed microscope, noticed microbial aggregates in oral samples [7]. The term \"biofilm\" was introduced by [PERSON], in 1985, in a brief report presenting microscopic photos of _Pseudomonas aeruginosa_ microcolonies residing in sputum samples of a cystic fibrosis patient. Although the presence of biofilms has its positive aspect in many ecosystems, these structures also exert their negative impact in the biomedical sector [4,8]. The ability of biofilm cells to survive in the environment with elevated concentrations of antimicrobial substances is termed \"recalcitrance\" and is a hallmark of treatment failures. In addition, biofilm cells have significantly lower sensitivity to unfavorable physicochemical factors and the activity of the immune system. The reduced susceptibility of biofilms results not only from the processes of passive tolerance to antimicrobials (decreased metabolism, matrix limiting the penetration of antibiotics, or presence of persister cells), but also from the processes of active increase in the number of resistant microorganisms (intensification of horizontal gene transfer (HGT) or induction of the hypermutable state) [4]. In association with the prevalence of biofilm formation and its negative impact on the infections treatment, in 2014, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) developed recommendations for microbiologists and physicians to improve the diagnosis of the most common infections accompanied by the biofilm presence [2]. The list of such diseases is wide and continues to grow, including: chronic otitis media/sinuses, endocarditis, lung infections associated with cystic fibrosis, urinary tract infections, vaginosis, osteomyelitisitis, chronic wound infections, catheter-related infections, and cancers of bile ducts and digestive system [4,5,8]. In the context of the last type of infections, attention should be focused strongly on spiral, Gram-negative rods colonizing the gastric mucosa--_Helicobacter pylori_[9,10]. _H. pylori_ has the ability to reside in the stomach for many years, often for a lifetime [11]. Although the presence of this bacterium may be associated with a number of gastrointestinal diseases, including gastric ulcers and cancers [12, 13, 14], more and more often the protective role against developing extra-gastric diseases, such as allergy, asthma, inflammatory bowel disease, or multiple sclerosis, is indicated [15, 16, 17]. Survival of _H. pylori_ in an unfavorable, gastric niche is enabled by an intensive urease secretion, a spiral shape, presence of numerous adhesins, and the production of cytotoxic proteins, e.g., vacuolating cytotoxoxin A (VacA) and cytotoxin-associated gene A (CagA) [18]. It is increasingly recognized, however, that the adaptive mechanisms of _H. pylori_ in the stomach may also be linked to the ability of this pathogen to form biofilms [19]. Nevertheless, this theme is still rarely discussed by scientists and despite the availability of results from original articles the number of reviews and exhaustion of _H.