## 3 Understanding Biofilms
### Biofilm Formation  
#### 3.3.1 Adhesion  
The first step in the development of biofilms is adhesion, a complex process involving various structural and molecular components. Flagella, pili, fimbiae, and specialized proteins are appendages that facilitate this process, with each element serving a unique role in helping microbial cells attach to surfaces [41; 42; 43]. Figure 3: Pathogenic effects of different types of biofilms at different sites. Flagella are essential for bacterial motility and play a critical role in chemotaxis, allowing bacteria to actively navigate toward favorable conditions and establish initial contact with surfaces. Chemotaxis enables microorganisms to move in response to chemical gradients, either toward beneficial stimuli or away from harmful ones [44]. Various biological systems control this survival mechanism. For example, in _E. coli_, chemotaxis is regulated by signaling arrays of chemotaxis protein paralogs, which coordinate signaling output [45]. Additionally, the _tonB_ gene has been shown to influence bacterial movement, chemotaxis, attachment, and biofilm formation in _Pseudomonas picoglossicida_[46]. Once bacteria reach a surface, alternative adhesion mechanisms reduce the functional significance of flagella in biofilm formation [41]. Fimbriae are critical for adhesion, particularly during the initial stages of biofilm formation. They enable bacteria to adhere to surfaces, other bacteria, or host cells, facilitating stable attachment [47; 48]. Pili also contribute to adhesion and movement, with certain types, such as Type IV pili, playing a key role in \"twitching motility\", which aids in disseminating and developing biofilms [49]. In addition to facilitating movement, pili are involved in intercellular adhesion within biofilms, contributing to the formation of intricate, layered structures. These structures enhance the ability of bacteria to effectively attach to and thrive on various surfaces [42]. Microbes that lack the ability to move use distinct methods for colonizing surfaces compared to their motile counterparts. These immobile bacteria rely heavily on surface chemicals and changes in the flow field around them to effectively adhere to surfaces. According to recent research, even slight modifications in the flow field are crucial for facilitating the adhesion of non-motile cells to adjacent surfaces [50]. Furthermore, outer sheath proteins have been proposed to play a significant role in colonizing microorganisms incapable of movement [51]. Pathogenic bacteria like _S. aureus_, for instance, can stick to epithelial surfaces by utilizing microbial surface components that recognize adhesive matrix molecules (MSCRAMMs). These components make the host more vulnerable to invasive infections [52]. The adhesion process is influenced by various factors, including the mechanical properties of the biofilm and the characteristics of the surface it adheres to. Biofilms possess the remarkable ability to modify the shape and structure of the surfaces they occupy through a process known as buckling adhesion, which can profoundly impact their interaction with the surface [53]. This dynamic interaction can also affect the physical environment. The initial phases of biofilm formation are influenced by physicochemical aspects such as surface charge, hydrophobicity, roughness, topography, and chemistry. The collective impact of these variables affects bacterial adherence, thus shaping the early development of biofilms [54]. The physical characteristics of surfaces hold significant sway over bacterial adherence and the creation of biofilms. Surface nanoroughness may affect bacterial adherence, with superhydrophobic surfaces reducing bacterial adhesion [55]. Recent studies have confirmed that submicron topography on surfaces can significantly reduce bacterial adhesion and prevent biofilm formation [56]. These insights have practical implications, including the development of antimicrobial coatings to reduce biofilm formation.