## 1 Introduction
Classically, pathogenic bacteria are classified as extracellular, facultative intracellular, and obligate intracellular. There is growing evidence that extracellular bacteria can survive inside host cells (mainly macrophages) where they hide from the immune system, survive in active or latent forms over prolonged intervals of time, and even proliferate. These bacteria lead to some of the most insidious infections that threaten human health and welfare globally. The main factors that contribute to this are: (i) rising antimicrobial resistance; (ii) increasing number of immunosuppressed patients; and (iii) healthcare-associated infections. The risk of developing an active disease is obviously higher among persons with compromised immune systems (elderly and transplant patients, HIV-positive cases, people with diabetes, cancer, autoimmune diseases, etc.). Intracellular infections are especially difficult to eliminate because the bacteria employ some ingenious mechanisms. These bacteria mainly reside inside phagocytic cells, but also find their way into non-phagocytic cells (epithelial cells, hepatocytes, fibroblasts, etc.). The host cells are not only primarily infected but also act as a reservoir for the bacteria, which can disseminate themselves in other tissues, leading to systemic infection. It has been proposed that bacterial pathogens should be labeled as exclusive extracellular, dual intracellular/extracellular or exclusive intracellular based on their infective lifestyle in the host [15]. Bacterial adhesion is the initial step in colonization and biofilm formation. Biofilms can be useful in environmental technologies and bioprocesses (for example, production of antibiotics, fermentation of food products, help in digestion); however, they can also cause infection, slime formation and pathogen contamination [16]. On the surface of pathogenic bacterial cells, one can usually find surface-associated molecules, called adhesins, that recognize eukaryotic surface components and mediate tight association with host tissues [17]. Adhesive molecules that also promote internalization of the microorganism are called invasins [17]. Bacterial adhesin and invasin recognize the host receptor, which determines the organ and tissue specificity and thus the entry site and mode of colonization as well [17]. Numerous adhesins and invasins can bind to multiple extracellular matrix (ECM) components and to transmembrane receptor molecules such as integrins [17]. Generally, bacteria do not distinguish between immobilized, soluble, and tissue-specific derivatives of ECMs [17]. The intracellular lifestyle provides certain advantages to pathogen bacteria: they are protected from the host immune system and antibiotics, they do not have to actuate energy-consuming adherence mechanisms to remain at the site of infection, they can access many nutrients in the cell cytoplasm, and they are likely to find good, stable physical conditions for growth [17; 18; 19]. Active invasion means that the bacterium can enter and diffuse into deeper subepithelial tissues to survive and systemically disseminate themselves in their hosts [17]. The glycocalyx is a mass of tangled fibers of LPS, other polysaccharides including branched sugar molecules that protrude from the surface of bacteria, surrounding a single cell or a colony of cells [18]. Glyocalyx-mediated adhesion determines the locations of bacteria in natural environments and the formation of biofilms (for example, tooth plaque). Glyocalyx fibers conserve and concentrate digestive enzymes released by the bacteria and directed against the host cell [18; 19]. In modern times, a lot of illnesses caused by pathogen bacteria can be medicated due to antibiotics, and antimicrobial and bacteria-repellent surfaces can be also created to reduce contamination [20]. However, during continuous exposure to antibacterial drugs, sequential chromosomal mutations can occur, leading to the appearance of resistance mechanisms step by step [21].